Advances in radiation delivery have expanded the scope of stereotactic body radiation therapy (SBRT) in lung cancer treatment, as it offers better local control, shorter treatments, and enhanced immunostimulation. This review summarizes recent literature regarding SBRT's role in nonoperable and operable early-stage, locally advanced, central, and oligometastatic nonsmall cell lung cancer (NSCLC), and its mixed results with immunotherapy.

Recent studies demonstrate SBRT achieves excellent local control in inoperable early-stage NSCLC and is being explored as an alternative to surgery for operable cases. Additionally, SBRT can be done safely in central tumors if strict dose limits to normal structures are observed. SBRT shows promise in locally advanced disease, as consolidative local therapy for oligoprogressive and oligometastatic disease and in combination with immune checkpoint inhibitors. Advances in adaptive radiation therapy and novel fractionation schedules, including ultra-hypofractionation and personalized approaches, further refine SBRT's role in lung cancer management, with more practice changing clinical trials on the horizon.

SBRT provides durable and well tolerated treatment for patients with localized and metastatic lung cancer. With ongoing trials exploring its synergy with immunotherapy and its applicability in operable patients and large tumors, SBRT is poised to play an even greater role in personalized lung cancer treatment.

There is paucity of data for thoracic in-field reirradiation with two courses of stereotactic ablative radiotherapy (SABR). This meta-analysis evaluates the safety and efficacy of repeat SABR as salvage therapy for in-field failures after definitive SABR.

A systematic search of PubMed, Cochrane Library, MEDLINE, and EMBASE databases was conducted in accordance with PRISMA guidelines. Studies were included if they involved adult patients treated with salvage SABR for in-field recurrences of lung cancer following prior SABR. To address varying definitions of local failure, studies were included if recurrence occurred within the original planning target volume (PTV). Studies with out-of-field failures (>1 cm from PTV) or those using non-SABR techniques were excluded. Pooled 1- and 2-year local control (LC) rates, overall survival (OS), and toxicities were calculated using a random-effects model. Population-weighted linear regression was employed to assess the relationship between dosimetric and clinico-pathologic variables and patient outcomes.

Twelve studies involving 197 patients were included in the quantitative analysis. All patients received two courses of SABR, with a median total dose of 50 Gy in 5 fractions. Pooled 1- and 2-year LC rates were 78.2 % (95 % CI: 66-87 %) and 68.0 % (95 % CI: 55-79 %), respectively. Patients receiving a cumulative biologically effective dose (BED) ≥ 200 Gy had significantly higher LC rates (84.9 %, 95 % CI: 70-93 %) vs (64.9 %, 95 % CI: 54-75 %, p = 0.02). Median OS did not significantly differ between low and high BED groups, though there was a trend toward improved survival with higher BED (21.4 vs 32.6 months). The pooled median OS across all studies was 26.3 months (95 % CI: 25.4-27.1). Improved LC rates were associated with smaller tumours (<2 cm), higher BED from the initial treatment and longer interval (>12 months) between initial and repeat SABR (p < 0.01). Toxicities were minimal, with a pooled incidence of ≥ grade 2 pneumonitis at 6.4 % and only 0.10 % reporting ≥ grade 3 toxicity.

Salvage in-field reirradiation with SABR achieves high local control and low toxicity, particularly in patients receiving higher cumulative BED (≥200 Gy) and with longer intervals (≥12 months) between treatments. These results suggest that repeat SABR is a viable salvage option for selected patients. Further prospective studies are needed to optimise dosing and patient selection for safe and effective reirradiation.

The treatment of early stage T1-T2N0M0 non-small cell lung cancers (NSCLC) was previously based on surgery. However, 20 to 25% of patients are inoperable due to their age, comorbidities or refuse surgery. Since 2018, stereotactic body radiation therapy (SBRT) has become the standard treatment for these patients. For operable patients, the comparison surgery - SBRT is difficult without a clear conclusion, the different phase III trials have not yet permitted to provide a formal answer in terms of local control and survival by default of inclusion. Dose and fractionation need to be selected according to tumor location. Tolerance is usually good, with few grade ≥3 toxicities; however, caution is advised for ultra-central tumors and in case of interstitial pneumonia. Post-therapeutic imaging monitoring is complex, sometimes with uncertainties between radiation-induced pneumonitis and relapse. This complexity may increase in ongoing trials combining SBRT and immunotherapy.

Lung cancer remains the leading cause of death worldwide, yet optimal treatment strategies for octogenarians with early-stage non-small cell lung cancer (NSCLC) remain unclear.

To investigate treatment patterns and survival outcomes in octogenarians and older with early-stage NSCLC.

A retrospective cohort study was conducted using Surveillance, Epidemiology, and End Results database. Patients aged ≥ 80 years with stage I-IIA NSCLC diagnosed between 2011 and 2020 were included. Primary treatments included surgery, radiation, and no treatment. Kaplan-Meier curves were used to evaluate overall survival (OS) and cancer-specific survival (CSS) stratified by treatment and year. Propensity score matching balanced clinical characteristics between surgery and radiation groups, followed by Cox regression analysis. Survival outcomes were further compared within matched subgroups stratified by tumor size.

Among 7,372 patients, median survival was 67 months for surgery and 33 months for radiotherapy. Radiotherapy use increased from 31.2% in 2011 to 49.4% in 2020, while surgery rates declined. Multivariate analysis (N = 2,434) showed radiotherapy was associated with worse OS (hazard ratio = 1.96, 95% CI = 1.78-2.15, P < 0.001) compared to surgery.

Radiotherapy is increasingly used to treat early-stage NSCLC in octogenarians, yet surgery provides superior long-term survival. Limitations of lack of detailed comorbidity data and differentiation between conventional radiotherapy and stereotactic ablative radiotherapy (SABR) may have expanded the advantages of surgery. Meanwhile, patient performance status and preferences must be considered in treatment decisions.

Surgery remains the preferred treatment option for eligible octogenarians with early-stage NSCLC.

There is currently no recognized assessment system to predict disease outcomes for stage I non-small cell lung cancer (NSCLC). This research aimed to develop a prognostic scoring system for predicting 5-year overall survival (OS) of individuals with stage I NSCLC following definitive therapeutic intervention. Additionally, the optimal number of examined lymph nodes (ELNs) count for tumors no larger than 30 mm was determined.

Patients (n=22,617) diagnosed with stage I NSCLC from 2007 to 2015 who underwent definitive treatment (pulmonary lobectomy, pulmonary sublobectomy, or radiotherapy) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. There were 400 Chinese patients with stage I NSCLC diagnosed in 2017 enrolled for external validation. The nomogram was constructed based on gradient boosting machine. The optimal ELNs in patients with tumors ≤30 mm and node-negative undergoing pulmonary lobectomy or pulmonary sublobectomy were determined using log-rank test and validated by multivariable analysis.

Age at diagnosis, histology, differentiated grade, tumor staging, number of ELNs, and definitive treatment pattern were recognized as important factors for 5-year OS. The prognostic scoring system exhibited superior discrimination accuracy, calibration ability, and net clinical benefit compared to the tumor, node, metastasis (TNM) staging system. For patients with tumors ≤30 mm, more than 10 and 20 ELNs demonstrated the maximum OS difference during lobectomy and sublobectomy, respectively.

This prognostic scoring system will anticipate the prognosis of stage I NSCLC patients after radical treatment, thereby offering individualized treatment recommendations for both clinicians and patients. A minimum of 10 ELNs during lobectomy and 20 ELNs during sublobectomy are necessary for small-sized NSCLC.

Stereotactic ablative radiotherapy (SABR) has emerged as an alternative, non-surgical treatment for high-risk patients with stage I non-small cell lung cancer (NSCLC) with increased use over time. The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) assembled an expert panel and conducted a systematic review of the literature evaluating the results of SABR, which is also referred to as stereotactic body radiation therapy (SBRT) or stereotactic radiosurgery (SRS), prior to developing treatment recommendations for high-risk patients with stage I NSCLC based on expert consensus. Publications detailing the findings of 16 prospective studies of SABR and 14 retrospective studies of SABR for the management of early-stage lung cancer in 54,697 patients were identified by systematic review of the literature with further review by members of our expert panel. Medical inoperability (93-95%) was the primary reason for utilizing SABR. The median rate of histologically confirmed cancer in treated patients was 67% (range 57-86%). In retrospective studies and prospective studies, the most common dosing regimens were 48-54Gy in 3-5 fractions and 44-66Gy in 3-5 fractions respectively. The median follow-up after SABR was 30 months (range 15-50). The complications, oncological results and quality of life after SABR in high-risk patients with early-stage NSCLC are summarized in this Expert Review article. Further prospective randomized trials are needed and are currently underway to compare outcomes after SABR with outcomes after sublobar resection to fully evaluate treatment options applicable this high-risk group of patients.

This paper highlights developments in diagnostic and nonsurgical local treatment modalities that have changed the management of early-stage lung cancer. These innovations aim to enhance diagnostic accuracy, minimize invasiveness, and improve patient outcomes. Liquid biopsies are emerging as promising tools for non-invasive diagnosis and monitoring, enabling earlier intervention without being standardized yet as well as not yet anchored in the guidelines. Endobronchial navigation has emerged as an innovative tool. By combining electromagnetic or GPS-like technology with 3D imaging and a steerable catheter, it enables accurate biopsy of small, peripheral lesions that were once challenging to sample, with a very low pneumothorax rate. Regarding nonsurgical treatments, stereotactic body radiotherapy (SBRT) continues to shine as a non-invasive local treatment modality for early-stage lung cancer and is the guideline-recommended standard-of-care for inoperable patients and patients refusing the risk of surgical resection. The low toxicity and excellent local control has made it an attractive alternative to surgery even in fitter patients. Percutaneous ablative techniques utilising energies such as microwave or pulse-field electroporation are options for patients who are not candidates for surgery or SBRT. Bronchoscopic ablation delivers the same energies but with a very lower pneumothorax rate and it is therefore also open to patients with multiple and bilateral lesions.

Surgery is the primary treatment for early-stage lung cancer. Patients with medically inoperable lung carcinomas and patients who refuse to undergo surgery are treated with definite radiotherapy. Stereotactic ablative radiotherapy (SABR) is a compelling non-invasive therapeutic modality for this group of patients that confers promising results.

We report an interim analysis of an ongoing trial. Eighty-one patients with medically inoperable early-stage (T1,2N0) lung cancer underwent SABR in our institution. SABR was delivered via the CyberKnife M6 robotic radiosurgery system. The endpoints of the analysis were treatment efficacy and tolerance.

There were no acute or late toxicities from the skin or the connective tissue of the thorax. A grade 2/3 lung injury of non-clinical significance was noted in 6% of patients, which was directly related to a higher biologically effective dose (BEDα/β = 3) and larger irradiation lung volumes in both univariate and multivariate analyses. A local control (LC) was achieved in 100% of the patients at the first follow-up, and the projected 24-month local progression-free survival (LPFS) rate was 95%. The projected 24-month disease-specific overall survival (OS) was 94%.

High LC and OS rates can be achieved with SABR for early-stage lung cancer, with minimal toxicity. This study continues to recruit patients.

To explore the survival effect of thoracic gross tumor volume (GTV) in three-dimensional (3D) radiotherapy for stage IV non-small cell lung cancer (NSCLC).

The data cases were obtained from a single-center retrospective analysis. From May. From 2008 to August 2018, 377 treatment criteria were enrolled. GTV was defined as the volume of the primary lesion and the hilus as well as the mediastinal metastatic lymph node. Chemotherapy was a platinum-based combined regimen of two drugs. The number of median chemotherapy cycles was 4 (2-6), and the cut-off value of the planning target volume (PTV) dose of the primary tumor was 63 Gy (30-76.5 Gy). The cut-off value of GTV volume was 150 cm3 (5.83-3535.20 cm3).

The survival rate of patients with GTV <150 cm3 is better than patients with GTV ≥150 cm3. Multivariate Cox regression analyses suggested that peripheral lung cancer, radiation dose ≥63 Gy, GTV <150 cm3, 4-6 cycles of chemotherapy, and CR + PR are good prognostic factors for patients with stage IV non-small cell lung cancer. The survival rate of patients with GTV <150 cm3 was longer than patients with ≥150 cm3 when they underwent 2 to 3 cycles of chemotherapy concurrent 3D radiotherapy (p < 0.05). When performing 4 to 6 cycles of chemotherapy concurrent 3D radiotherapy, there was no significant difference between <150 cm3 and ≥150 cm3.

The volume of stage IV NSCLC primary tumor can affect the survival of patients. Appropriate treatment methods can be opted by considering the volume of tumors to extend patients' lifetime to the utmost.

Surgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer.

We report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings.

A total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), is undoubtedly one of the major breakthroughs in lung cancer research. Patient survival and prognosis have all been improved as a result, although numerous patients do not respond to immunotherapy due to various immune escape mechanisms of the tumor cells. Recent preclinical and clinical evidence has shown that stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy, has a prominent immune priming effect that could elicit antitumor immunity against specific tumor antigens and destroy distant tumor cells, thereby achieving the elusive abscopal effect, with the resulting immuno‑active tumor environment also being more conducive to ICIs. Some landmark trials have already demonstrated the survival benefit of the dynamic duo of SBRT plus immunotherapy in metastatic non‑small‑cell lung cancer, while others such as PEMBRO‑RT further suggest that the addition of SBRT to immunotherapy could expand the current indication to those who have historically responded poorly to ICIs. In the present review, the biological mechanisms that drive the synergistic effect of SBRT and immunotherapy were first briefly outlined; then, the current understanding from clinical trials was summarized and new insight into the evolving role of immunotherapy and SBRT synergy in lung cancer treatment was provided. Finally, novel avenues for discovery were highlighted. The innovation of the present review lies in the inclusion of non‑ICI immunotherapy in the discussion, which provides a more comprehensive view on the current development and future trend of SBRT + immunotherapy synergy.

To investigate the clinical impact of plan complexity on the local recurrence-free survival (LRFS) of non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT).

Data from 123 treatment plans for 113 NSCLC patients were analyzed. Plan-averaged beam modulation (PM), plan beam irregularity (PI), monitor unit/Gy (MU/Gy) and spherical disproportion (SD) were calculated. The γ passing rates (GPR) were measured using ArcCHECK 3D phantom with 2 %/2mm criteria. High complexity (HC) and low complexity (LC) groups were statistically stratified based on the aforementioned metrics, using cutoffs determined by their significance in correlation with survival time, as calculated using the R-3.6.1 packages. Kaplan-Meier analysis, Cox regression, and Random Survival Forest (RSF) models were employed for the analysis of local recurrence-free survival (LRFS). Propensity-score-matched pairs were generated to minimize bias in the analysis.

The median follow-up time for all patients was 25.5 months (interquartile range 13.4-41.2). The prognostic capacity of PM was suggested using RSF, based on Variable Importance and Minimal Depth methods. The 1-, 2-, and 3-year LRFS rates in the HC group were significantly lower than those in the LC group (p = 0.023), when plan complexity was defined by PM. However, no significant difference was observed between the HC and LC groups when defined by other metrics (p > 0.05). All γ passing rates exceeded 90.5 %.

This study revealed a significant association between higher PM and worse LRFS in NSCLC patients treated with SBRT. This finding offers additional clinical evidence supporting the potential optimization of pre-treatment quality assurance protocols.

Histology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiotherapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). A histology-driven SBRT approach has not been explored in routine clinical practice and histology-dependent fractionation schemes remain unknown. Here, we analyzed pooled histologic TCP data as a function of biologically effective dose (BED) to determine histology-driven fractionation schemes for SBRT and hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC).

The least-χ2 method was used to fit the collected histologic TCP data of 8510 early-stage NSCLC patients to determine parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative.

A fit to the histologic TCP data yielded independent radiobiological parameter sets for radiotherapy of early-stage lung ADC and SCC. TCP increases steeply with BED and reaches an asymptotic maximal plateau, allowing us to determine model-independent optimal fractionation schemes of least doses in 1-30 fractions to achieve maximal tumor control for early-stage lung ADC and SCC, e.g., 30, 44, 48, and 51 Gy for ADC, and 32, 48, 54, and 58 Gy for SCC in 1, 3, 4, and 5 fractions, respectively.

We presented the first determination of histology-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. These proposed optimal fractionation schemes provide first insights for histology-based personalized radiotherapy of two predominant early-stage NSCLC subtypes ADC and SCC, which require further validation with large-scale histologic TCP data.

The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in "fit," operable patients as well, so SBRT would be eligible in place of surgery.

This study aims to assess the dosimetry and treatment efficiency of TaiChiB-based Stereotactic Body Radiotherapy (SBRT) plans applying to treat two-lung lesions with one overlapping organs at risk.

For four retrospective patients diagnosed with two-lung lesions each patient, four treatment plans were designed including Plan Edge, TaiChiB linac-based, RGS-based, and a linac-RGS hybrid (Plan TCLinac, Plan TCRGS, and Plan TCHybrid). Dosimetric metrics and beam-on time were employed to evaluate and compare the TaiChiB-based plans against Plan Edge.

For Conformity Index (CI), Plan TCRGS outperformed all other plans with an average CI of 1.06, as opposed to Plan Edge's 1.33. Similarly, for R50 %, Plan TCRGS was superior with an average R50 % of 3.79, better than Plan Edge's 4.28. In terms of D2 cm, Plan TCRGS also led with an average of 48.48%, compared to Plan Edge's 56.25%. For organ at risk (OAR) sparing, Plan TCRGS often displayed the lowest dosimetric values, notably for the spinal cord (Dmax 5.92 Gy) and lungs (D1500cc 1.00 Gy, D1000cc 2.61 Gy, V10 Gy 15.14%). However, its high Dmax values for the heart and great vessels sometimes exceeded safety thresholds. Plan TCHybrid presented a balanced approach, showing doses comparable to or better than Plan Edge without crossing safety limits. In terms of beam-on time, Plan TCLinac emerged as the most efficient treatment option in three out of four cases, followed closely by Plan Edge in one case. Plan TCRGS, despite its dosimetric advantages, was the least efficient, recording notably longer beam-on times, with a peak at 33.28 minutes in Case 2.

For patients with two-lung lesions treated by SBRT whose one lesion overlaps with OARs, the Plan TCHybrid delivered by TaiChiB digital radiotherapy system can be recommended as a clinical option.

Disease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20-40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression.

Published CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122). Features were associated with progression-free survival (PFS) using bootstrapped Cox regression (Bonferroni-corrected univariate predictor: p ≤ 0.002) and only non-strongly correlated predictors were retained (|Rs|<0.70) in forward-stepwise multivariate analysis.

Tumor diameter and SUVmax were the two most frequently reported features associated with progression/survival (in 6/20 and 10/20 identified studies). These two features and 12 of the 15 additional features (CT: 6; PET: 6) were candidate PFS predictors. A re-fitted model including diameter and SUVmax presented with the best performance (c-index: 0.78; log-rank p-value < 0.0001). A model built with the two best additional features (CTspiculation1 and SUVentropy) had a c-index of 0.75 (log-rank p-value < 0.0001).

A re-fitted pre-treatment model using the two most frequently published features - tumor diameter and SUVmax - successfully stratified early-stage NSCLC patients by PFS after receiving SBRT.

In recent years, immune checkpoint inhibitors (ICIs) have become a widely used treatment for non-small cell lung cancer (NSCLC), and the combination with traditional radiotherapy (RT) has shown significant potential in prolonging patient survival. However, both thoracic RT and ICIs can lead to cardiac toxicity, including radiation-induced heart damage (RIHD) and immunotherapy-related heart damage (IRHD). It still remains uncertain whether the combination of thoracic RT and immunotherapy will exacerbate acute or late cardiovascular (CV) toxicity and incidence. In this review, we summarize safety data from relevant clinical studies regarding CV toxicity for the combination therapy in NSCLC patients, explore the underlying synergetic mechanisms and common risk factors, and proposed treatment and management strategies. We hope to increase emphasis on the long-term assessment of CV toxicity risks associated with the combination therapy, and reduce the incidence of CV deaths resulting from such regimens.

Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. We found that APE1 was significantly upregulated in LUAD tissues compared to para-carcinoma tissues and promoted the proliferation and invasion of LUAD cells in vitro and in vivo. Mechanistically, APE1 inhibited pyroptosis by inactivating the interferon gene stimulator (STING) pathway via direct interaction with AIM2 and DDX41, as detected by RNA-seq and co-immunoprecipitation. APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. It can induce pyroptosis and is negatively regulated by interactions with AIM2 and DDX41. Therefore, APE1 inhibitors should be considered to enhance the radiosensitivity of LUAD cells and improve patient prognosis and therapeutic outcomes. Thus, APE1 play a role in the tumor immune microenvironment and in tumor immunotherapy.

Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC.

We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older with histologically proven treatment-naive stage IA-IB (tumour size ≤4 cm, N0M0), stage IIA (tumour size ≤5 cm, N0M0), or stage IIB (tumour size >5 cm and ≤7 cm, N0M0) as per the American Joint Committee on Cancer version 8 staging system or isolated parenchymal recurrences (tumour size ≤7 cm) NSCLC (TanyNanyM0 before definitive surgery or chemoradiotherapy) were included in this trial. Participants were randomly assigned (1:1; using the Pocock & Simon method) to receive SABR with or without four cycles of nivolumab (480 mg, once every 4 weeks, with the first dose on the same day as, or within 36 h after, the first SABR fraction). This trial was unmasked. The primary endpoint was 4-year event-free survival (local, regional, or distant recurrence; second primary lung cancer; or death). Analyses were both intention to treat (ITT) and per protocol. This trial is registered with ClinicalTrials.gov (NCT03110978) and is closed to enrolment.

From June 30, 2017, to March 22, 2022, 156 participants were randomly assigned, and 141 participants received assigned therapy. At a median 33 months' follow-up, I-SABR significantly improved 4-year event-free survival from 53% (95% CI 42-67%) with SABR to 77% (66-91%; per-protocol population, hazard ratio [HR] 0·38; 95% CI 0·19-0·75; p=0·0056; ITT population, HR 0·42; 95% CI 0·22-0·80; p=0·0080). There were no grade 3 or higher adverse events associated with SABR. In the I-SABR group, ten participants (15%) had grade 3 immunologial adverse events related to nivolumab; none had grade 3 pneumonitis or grade 4 or higher toxicity.

Compared with SABR alone, I-SABR significantly improved event-free survival at 4 years in people with early-stage treatment-naive or lung parenchymal recurrent node-negative NSCLC, with tolerable toxicity. I-SABR could be a treatment option in these participants, but further confirmation from a number of currently accruing phase 3 trials is required.

Bristol-Myers Squibb and MD Anderson Cancer Center Alliance, National Cancer Institute at the National Institutes of Health through Cancer Center Core Support Grant and Clinical and Translational Science Award to The University of Texas MD Anderson Cancer Center.

Although the effects of estimated dose of radiation to immune cells (EDRIC) in stage III NSCLC, LA-NSCLC, LS-SCLC and esophageal cancer on clinical outcomes have been studied, its impact in early-stage non-small cell lung cancer (ES-NSCLC) is unknown. In this study, we evaluated the role of EDRIC and identified the factors influencing EDRIC in this population.

We retrospectively analyzed 211 pathologically confirmed ES-NSCLC patients who were treated with SBRT between 2007 and 2020. EDRIC was calculated based on the model developed by Jin et al. and improved by Ladbury et al. Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate CSS, PFS, LPFS, and DMFS. Pearson correlation was used to assess the correlation between variables. We further validated our findings in an independent cohort of 119 patients with ES-NSCLC.

A total of 211 patients were included with median follow-up of 48 months in the training cohort. The median EDRIC was 2.178 Gy (range: 0.426-6.015). GTV showed a positive correlation with EDRIC (r = 0.707, P = 0.000). In multivariate analysis, higher EDRIC was significantly associated with worse CSS (HR = 1.468, P = 0.009) and DMFS (HR = 1.491, P = 0.016). Considering each EDRIC quartile, there was a significant difference in CSS between 1st and 4th and 1st and 3rd quartile (P = 0.000, P = 0.004, respectively); and DMFS between 1st and 4th,1st and 3rd, and 1st and 2nd quartile (P = 0.000, P = 0.000, P = 0.008, respectively). In the subgroup and validation cohort, EDRIC was also the important prognostic predictor of CSS and DMFS using multivariate analysis.

EDRIC was an independent predictor of CSS and DMFS in ES-NSCLC, and it was affected by GTV and tumor location. Though EDRIC is a critical determinant of treatment outcomes, it is quantifiable and potentially modifiable. Additional researches exploring the feasibility of achieving lower EDRIC while maintaining adequate tumor coverage during radiotherapy are warranted.

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n = 4, 67%), concurrent anticoagulant therapy (n = 1, 17%) and concurrent systemic therapy (n = 4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n = 130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH.

The therapeutic interventions against lung cancer are currently based on a fully personalized approach to the disease with considerable improvement of patients' outcome. Alongside continuous scientific progresses and research investments, massive technologic efforts, innovative challenges, and consolidated achievements together with research investments are at the bases of the engineering and manufacturing revolution that allows a significant gain in clinical setting.

The scope of this review is thus to focus, rather than on the biologic traits, on the analysis of the precision sensors and novel generation materials, as semiconductors, which are below the clinical development of personalized diagnosis and treatment. In this perspective, a careful revision and analysis of the state of the art of the literature and experimental knowledge is presented.

Novel materials are being used in the development of personalized diagnosis and treatment for lung cancer. Among them, semiconductors are used to analyze volatile cancer compounds and allow early disease diagnosis. Moreover, they can be used to generate MEMS which have found an application in advanced imaging techniques as well as in drug delivery devices.

Overall, these issues represent critical issues only partially known and generally underestimated by the clinical community. These novel micro-technology-based biosensing devices, based on the use of molecules at atomic concentrations, are crucial for clinical innovation since they have allowed the recent significant advances in cancer biology deciphering as well as in disease detection and therapy. There is an urgent need to create a stronger dialogue between technologists, basic researchers, and clinicians to address all scientific and manufacturing efforts towards a real improvement in patients' outcome. Here, great attention is focused on their application against lung cancer, from their exploitations in translational research to their application in diagnosis and treatment development, to ensure early diagnosis and better clinical outcomes.

For patients receiving lung stereotactic ablative radiotherapy (SABR), evidence suggests that high peritumor density predicts an increased risk of microscopic disease (MDE) and local-regional failure, but only if there is low or heterogenous incidental dose surrounding the tumor (GTV). A data-mining method (Cox-per-radius) has been developed to investigate this dose-density interaction. We apply the method to predict local relapse (LR) and regional failure (RF) in patients with non-small cell lung cancer.

199 patients treated in a routine setting were collated from a single institution for training, and 76 patients from an external institution for validation. Three density metrics (mean, 90th percentile, standard deviation (SD)) were studied in 1mm annuli between 0.5cm inside and 2cm outside the GTV boundary. Dose SD and fraction of volume receiving less than 30Gy were studied in annuli 0.5-2cm outside the GTV to describe incidental MDE dosage. Heat-maps were created that correlate with changes in LR and RF rates due to the interaction between dose heterogeneity and density at each distance combination. Regions of significant improvement were studied in Cox proportional hazards models, and explored with and without re-fitting in external data. Correlations between the dose component of the interaction and common dose metrics were reported.

Local relapse occurred at a rate of 6.5% in the training cohort, and 18% in the validation cohort, which included larger and more centrally located tumors. High peritumor density in combination with high dose variability (0.5 - 1.6cm) predicts LR. No interactions predicted RF. The LR interaction improved the predictive ability compared to using clinical variables alone (optimism-adjusted C-index; 0.82 vs 0.76). Re-fitting model coefficients in external data confirmed the importance of this interaction (C-index; 0.86 vs 0.76). Dose variability in the 0.5-1.6 cm annular region strongly correlates with heterogeneity inside the target volume (SD; ρ = 0.53 training, ρ = 0.65 validation).

In these real-world cohorts, the combination of relatively high peritumor density and high dose variability predicts increase in LR, but not RF, following lung SABR. This external validation justifies potential use of the model to increase low-dose CTV margins for high-risk patients.

Until the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm with consolidation ICIs following definitive concurrent chemoradiotherapy has been the standard of care since the PACIFIC trial. Preclinical evidence has demonstrated the role of RT in the cancer-immune cycle and the synergistic effect of RT combined with ICIs (iRT). However, RT exerts a double-edged effect on immunity and the combination strategy still could be optimized in many areas. In the context of LA-NSCLC, optimized RT modality, choice, timing, and duration of ICIs, care for oncogenic addicted tumors, patient selection, and novel combination strategies require further investigation. Targeting these blind spots, novel approaches are being investigated to cross the borders of PACIFIC. We discussed the development history of iRT and summarized the updated rationale for the synergistic effect. We then summarized the available research data on the efficacy and toxicity of iRT in LA-NSCLC for cross-trial comparisons to eliminate barriers. Progression during and after ICIs consolidation therapy has been regarded as a distinct resistance scenario from primary or secondary resistance to ICIs, the subsequent management of which has also been discussed. Finally, based on unmet needs, we probed into the challenges, strategies, and auspicious orientations to optimize iRT in LA-NSCLC. In this review, we focus on the underlying mechanisms and recent advances of iRT with an emphasis on future challenges and directions that warrant further investigation. Taken together, iRT is a proven and potential strategy in LA-NSCLC, with multiple promising approaches to further improve the efficacy. Video Abstract.

Salvage surgery refers to operative resection of persistent or recurrent disease in patients initially treated with intention-to-cure nonoperative management. In non-small-cell lung cancer, salvage surgery may be effective in treating selected patients with locally progressive tumors, recurrent local or locoregional disease, or local complications after nonoperative therapy. Importantly, those patients who may be candidates for salvage surgery are evolving, in terms of disease stage as well as the types of attempted definitive therapy received.

Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better treatment plan optimization and more accurate dose calculation. We expect to re-start the SBPT program, including for early stage NSCLC as well as for other disease sites soon after starting patient treatment at our new proton therapy center.

A 62-year-old woman with a 40-pack-year smoking history and severe chronic obstructive pulmonary disease with early-stage right upper lobe non-small cell lung cancer (NSCLC) was treated with stereotactic ablative radiotherapy (SABR). Two years after treatment, a surveillance computerized tomography scan showed lesions of the posterior 4th and 5th ribs including expansion of the medulla that was unusual and of concern for possible malignant infiltration. A follow-up magnetic resonance imaging (MRI) scan revealed these lesions to be healing fractures post-radiotherapy. Although generally well tolerated, SABR is known to produce inflammatory and fibrotic changes both in-field and in organs at risk, and rib fractures are a well-established adverse event. MRI has high diagnostic accuracy and sensitivity for rib fractures and was able to rule out malignant spread. This case demonstrates the need for regular follow-up following SABR for early-stage NSCLC, as well as the challenge of interpreting indeterminate post-SABR radiography findings.

To establish the dose effect relationship between the dose parameters of stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) and the local tumor control rate.

A comprehensive literature search was conducted using PubMed, the Web of Science and the Cochrane databases to determine the articles treated with SBRT in early-stage NSCLC. Original studies with complete prescription dose information, tumor local control rate and other important parameters were screened and reported. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as a statistically significant level.

After literature screening, 22 eligible studies were included in probit model regression analysis, involving 1861 patients. There is no significant dose effect relationship between nominal BED₁₀ and peripheral BED₁₀ versus 3 years local control probability. There were significant dose effect relationships between the center BED₁₀ and the average BED₁₀ versus the 3 years local control probability, with P values are 0.001 and < 0.0001, respectively. According to the results of this model, the 3 years local control rate of 90.5% (87.5-92.1%) and 89.5% (86.7-91.0%) can be expected at the center BED₁₀ of 180 Gy or the average BED₁₀ of 140 Gy, prospectively.

For NSCLC treated with SBRT, more attention should be paid to the central dose and average dose of PTV. A set of clear definition in the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Mufangji decoction (MFJD), a famous traditional Chinese medicine formula in Synopsis of Golden Chamber (Jingui yaolue), has been utilized to treat cough and asthma and release chest pain over 2000 years in China. Chinese old herbalist doctor use MFJD to treat lung cancer and cancerous pleural fluid, but the preventive effect of MFJD on lung cancer and the underlying mechanism are indefinite.

The goal of this study is to explore the efficacy and mechanism of Mufangji decoction preventing lung cancer referring to the traditional use.

Tumor allograft experiment and host versus tumor experiment were used to observe the direct anti-tumor effect and indirect anti-tumor immune effect, the mouse lung carcinogenic model was used to evaluate the dose-response and the preventive effect of MFJD on lung cancer. The active ingredients of MFJD were obtained by UPLC-MS/MS. The potential targets of MFJD were screened by network pharmacology and transcriptomics. The therapeutic targets and pathways of MFJD on lung cancer were obtained by protein-protein interaction, molecular docking and David database. The predicted results were verified in vitro and in vivo.

MFJD could significantly prevent tumor growth in host versus tumor experiment but could not in tumor allograft experiment, indicating an anti-tumor immune effect against lung cancer. MFJD could reduce lung nodules with a dose-response in mouse lung carcinogenic model. Myeloperoxidase (MPO) was selected as the core target due to the highest degree value in Protein-Protein interaction network and had potently binding activity to sinomenine and dehydrocostus lactone in molecular docking. In vivo, MPO-expressed neutrophils are negatively correlated with lung cancer progression and MFJD could promote the neutrophil-related immune surveillance. In vitro, sinomenine and dehydrocostus lactone could promote neutrophil phagocytosis, MPO and ROS production in a dose dependent manner. The major compounds from MFJD were identified to regulate 36 targets for lung cancer prevention by UPLC-MS/MS, network pharmacology and transcriptomics. David database exhibited that MFJD plays an important role in immunoregulation by modulating 4 immune-related biological processes and 3 immune-related pathways.

MFJD prevents lung cancer by mainly promoting MPO expression to maintain neutrophil immune surveillance, its key compounds are sinomenine and dehydrocostus lactone.

For early stage medically inoperable lung cancer treated with fractionated stereotactic body radiotherapy (SBRT), higher local failure is associated with squamous carcinoma (SqC) compared to adenocarcinoma (AC). This study explored whether histology influences single-fraction SBRT local control.

We surveyed our prospective data registry from 12/2009 to 12/2019 for SF-SBRT cases with biopsy-proven AC or SqC only. Outcomes of interest included local (LF), nodal (NF), distant (DF) failure rates and overall survival (OS), as well as treatment-related toxicity.

For the 10-year interval surveyed, 113 patients met study criteria. There was no association between histology and dose received (34 Gy or 30 Gy). Median follow up was 22.9 months. Patient characteristics were balanced between histologic cohorts. Median tumor size was 1.9 cm. Comparing total AC vs. SqC cohorts, 2-year LF rates (%) were 7.3 vs. 9.6, respectively (P = .9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.8 vs. 6.4; 10.5 vs. 16.2; 15.8 vs. 13.0; 77.9 vs.71.2 (all P = non-significant). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.8 vs. 8.1; 5.9 vs. 18.0; 23.5 vs. 9.7; 70.6 vs. 77.1 (all P = non-significant). When considering toxicities, there were no grade 4/5 toxicities and no significant differences in any other toxicity rate by histology or dose.

SF-SBRT local control was not associated with histology, unlike fractionated schedules. This novel finding adds to the evolving understanding of this treatment schedule.

This study aimed to assess indicators of type 2 diabetes mellitus (DM) management, including adequate DM control, and treatment rates, in cancer survivors according to the time of DM diagnosis and to compare them with the DM management indicators of a non-cancer control group.

We used the 2013-2019 data of the Korea National Health and Nutrition Examination Survey for this study. To compare their adequate DM control, and treatment rates, we identified 4918 patients with type 2 DM aged ≥ 30 years and classified them into pre-existing diabetes, pre-existing cancer, and diabetes without cancer groups. Predictors of adequate glycemic control and diabetes treatment were analyzed using binary logistic regression.

Diabetes without cancer group had higher fasting blood glucose and glycosylated hemoglobin A1c levels and lower adequate glycemic control than did the other two groups. The preexisting cancer group had low treatment rates. After adjusting for age, gender, employment status, and duration of diabetes, the preexisting cancer group had 0.51-fold lower odds of receiving treatment, such as insulin injection or oral diabetes medications, than the other two groups (adjusted odds ratio, 0.50; 95% confidence interval, 0.38-0.66).

Cancer survivors had lower fasting glucose and HbA1c than those with diabetes without cancer. However, as a result of the sub-analysis, the treatment rate of the pre-existing cancer group was significantly lower than that of diabetes without cancer. Based on these results, cancer survivors' care-related healthcare workers should be aware of the need for monitoring blood sugar even in cancer survivors without underlying diabetes mellitus and pay more attention to early detection and active treatment of diabetes.

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

In the present study, we aim to show the results of microwave ablation (MWA) for medically inoperable stage I non-small cell lung cancers (NSCLCs) with long-term follow-up.

From Feb 2011 to Mar 2016, patients with histologically proven clinical stage I NSCLC were treated with CT-guided MWA and retrospectively analyzed. The primary end point was overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and complications.

A total of 105 patients with 105 lesions underwent MWA. The mean age was 70.7 years (range: 40-86 years), and the mean diameter of all lesions was 2.40 cm (range: 0.9-4.0 cm). Adenocarcinoma was the most common histological type (77, 73.3%), followed by squamous cell carcinomas (21, 20%) and undefined NSCLC (7, 6.7%). With a median follow-up of 54.8 months, the median DFS was 36.0 months, and 1-, 3-, and 5-year DFS rates were 89.5%, 49.4%, and 42.7%, respectively. The median CSS and OS were 89.8 and 64.2 months, respectively. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years, while the CSS rates were 99%, 78.9%, and 60.9%, respectively. Patients with stage IB lesions had significant shorter DFS (22.3 months vs. undefined, HR: 11.5, 95%CI: 5.85-22.40) and OS (37.3 vs. 89.8 months, HR: 8.64, 95% CI: 4.49-16.60) than IA disease.

MWA is a safe, effective, and potentially curative therapy for medically inoperable stage I NSCLC patients.

• In this multicenter retrospective study which included 105 patients, we found the median overall survival (OS) was 64.2 months. The OS rate was 99% at 1 year, 75.6% at 3 years, and 54.1% at 5 years. • Procedures were technically successful and well tolerated in all patients. Most MWA complications were mild or moderate.

Lobar resection has been the established standard of care for peripheral early-stage non-small cell lung cancer (NSCLC). Over the last few years, surgical lung sparing approach (sublobar resection [SLR]) has been compared with lobar resection in T1N0 NSCLC. Three nonsurgical options are available in those patients who have a prohibitive surgical risk, and those who refuse surgery: stereotactic body radiotherapy (SBRT), percutaneous ablation, and bronchoscopic ablation. Local ablation involves placement of a probe into a tumor, and subsequent application of either heat or cold energy, pulsing electrical fields, or placement of radioactive source under an image guidance to create a zone of cell death that encompasses the targeted lesion and an ablation margin. Despite being in their infancy, the bronchoscopic ablative techniques are undergoing rapid research, as they extrapolate a significant knowledge-base from the percutaneous techniques that have been in the radiologist's armamentarium since 2000. Here, we discuss selected endoscopic and percutaneous thermal and non-thermal therapies with the focus on their efficacy and safety.

Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).

PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.

Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87-1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71-1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25-1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR = 1.32, 95% CI: 1.14-1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64-1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63-6.07, P = 0.25) between the LTA group and SBRT group.

Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.

INPLASY202160099.

Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making.

A PubMed systematic review from 2000-2021 of outcomes after SBRT or thermal ablation vs. resection is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons with at least some adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved.

Short-term outcomes are meaningfully better after SBRT than resection. SBRT doesn't affect quality-of-life (QOL), on average pulmonary function is not altered, but a minority of patients may experience gradual late toxicity. Adjusted non-randomized comparisons demonstrate a clinically relevant detriment in long-term outcomes after SBRT vs. surgery. The short-term benefits of SBRT over surgery are accentuated with increasing age and compromised patients, but the long-term detriment remains. Ablation is associated with a higher rate of complications than SBRT, but there is little intermediate-term impact on quality-of-life or pulmonary function tests. Adjusted comparisons show a meaningful detriment in long-term outcomes after ablation vs. surgery; there is less difference between ablation and SBRT.

A systematic, comprehensive summary of evidence regarding Stereotactic Body Radiotherapy or thermal ablation vs. resection with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation for a framework for individualized decision-making.