Inoperable Early-stage Non-small Cell Lung Research Articles

Survival analysis after stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a single-institution cohort study

BackgroundStereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality.MethodsFrom August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3–5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30–33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI).ResultsThe median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01–2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06–2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58).ConclusionSABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.

Invasive Nodal Staging via Endobronchial Ultrasound and Outcome in Patients Treated with Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer – Results from a Single Institution Study

IntroductionStereotactic body radiation therapy (SBRT) is an effective treatment for medically inoperable early-stage non-small cell lung cancer (NSCLC). The prognostic value of invasive nodal staging (INS) for patients undergoing SRBT has not been studied extensively. Herein, we report the impact of INS in addition to 18F-FDG-PET on treatment outcome for patients with NSCLC undergoing SBRT. Materials and MethodsPatients with stage I/ II NSCLC who underwent SBRT were included with IRB approval. Clinical, dosimetric, and radiological data were obtained. Overall survival (OS), regional recurrence free survival (RRFS), local recurrence free survival (LRFS), and distant recurrence free survival (DRFS) were analyzed using Kaplan Meyer method. Univariable analysis (UVA) and multivariable analysis (MVA) were performed to assess the relationship between the variables and the outcomes. ResultsA total of 376 patients were included in the analysis. Median follow up was 43 months (IQ 32.6-45.8). Median OS, LRFS, RRFS, DRFS were 40, 32, 32, 33 months, respectively. The 5-year local, regional, and distant failure rates were 13.4%, 23.5% and 25.3%, respectively. The 1-year, 3-year and 5-year OS were 83.8%, 55.6%, and 36.3%, respectively. On MVA, INS was not a predictor of either improved overall or any recurrence free survival endpoints while larger tumor size, age, and adjusted Charleston co-morbidity index (aCCI) were significant for inferior LRFS, RRFS, and DRFS. ConclusionInvasive nodal staging did not improve overall or recurrence free survival among patients with early-stage NSCLC treated with SBRT whereas older age, aCCI, and larger tumor size were significant predictors of LRFS, RRFS, and DRFS.

Could Poor Outcomes for Patients with Limited Lung Function Treated with SAbR Necessitate PULSAR?

Stereotactic ablative radiotherapy (SAbR) employs precise targeting and delivery of ablative radiation doses in patients with medically inoperable early-stage non-small cell lung cancer, as well as patients with pulmonary metastases. SAbR is well tolerated with few studies reporting a minimal decline in pulmonary function tests (PFTs). However, poor pulmonary function is considered a risk factor for radiation induced lung toxicity. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) is an adaptive radiation therapy regimen where radiation pulses are delivered over longer periods of time, thereby allowing for modification of the treatment based on the patient's response, as well as limiting toxicities. As such, we hypothesize that treating patients with poor pulmonary function using a PULSAR approach is better tolerated in when compared to patients treated with SAbR. We performed a retrospective review of our institutional database of patients treated with SAbR to lung lesions from 2005 to 2022. We assessed the overall survival in stage-matched patients with normal vs poor lung function who received SAbR (40 patients in each cohort). Patients with decreased lung function included those with a diagnosis of moderate/severe COPD, restrictive lung disease, or patients needing home oxygen at the time of treatment. We then analyzed PFTs changes for patients receiving SAbR, and evaluated these changes relative to treatment delivery. Stage-matched Kaplan-Meier analysis of patients with normal vs poor lung function receiving SAbR revealed a statistically significant difference in survival with Log-rank test p = 0.007. Of the patients with PFTs, 45 (90%) received SAbR with two to three treatments weekly, while 5 (10%) were treated on a PULSAR regimen with one fraction every week to three weeks. No trends or significant differences are observed in the changes of total lung capacity (TLC), the first second of exhalation (FEV1), forced vital capacity (FVC) or FEV1/FVC ratios. However, we did note variations in the diffusing capacity of the lung for carbon monoxide (DLCO). The mean difference in DLCO for the SAbR and PULSAR groups were -26.07% (95% CI: -31.28 to -20.87, p < 0.0001), and -10.52% (95% CI: -40.74 to 19.69, p = 0.388), respectively. We observed a significant difference in overall survival between patients with normal vs poor lung function receiving SAbR. In a preliminary analysis, we discovered a small decline in DLCO for patients treated with regularly scheduled SAbR treatments. In the patients treated on the PULSAR regimen, however, this change in DLCO is not statistically significant. While this data suggests that increasing the time frame between individual doses of radiation may result in better toleration of radiotherapy in this patient population, the sample size of patients treated via PULSAR is limited, and longer follow-up is needed to further evaluate the potential benefits.

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n=163) and follow-up FDG-PET/CT at 3 or 6 months (n=71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P=.006), >12.3 for PFS (aHR, 2.80, P=.011), and >12.6 for OS (aHR, 3.00, P=.003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P=.018), and 53% at 6 months (aHR, 0.12, P=.046) were associated with improved local failure-free survival. Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

The Impacts of Angiotensin Receptor Blockers (ARBs) or Angiotensin-Converting Enzyme Inhibitors (ACEIs) on Patients with Stereotactic Body Radiation Therapy (SBRT) for Early-Stage NSCLC

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an alternative to surgery for patients with inoperable early-stage non-small cell lung cancer (NSCLC). The majority of inoperable NSCLC patients are elderly and frequently have comorbidities including cardiovascular diseases for which they frequently receive angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs). The interactions of these medications with SBRT are not clear. The objective of the current study is to investigate the interaction of ARBs and ACEIs with SBRT for the outcomes of early-stage NSCLC. Methods and Materials: A retrospective chart review of patients treated with SBRT for Stage I and II NSCLC (AJCC 7th edition) at a single institution between 2006 and 2017 was conducted. Information on the use of ARBs, ACEIs, demographics, and tumor-related factors was collected. Kaplan-Meier and Cox proportional hazard analyses were performed to assess the impact of ARBs and ACEIs combined with SBRT respectively on the treatment outcomes of these patients. Results: In total, 116 patients were included in the study, among whom 38/116 (32.76%) received ACEIs, and 20/116 (17.24%) received ARBs. In the multivariable analysis, the use of ARBs, but not ACEIs, with SBRT, was significantly associated with the increased risk of dissemination (Hazard Ratio (HR): 2.97; CI: 1.40-6.27; p &lt; 0.004) compared to SBRT without ARBs. The tumor size of &gt; = 3 cm was associated with significantly decreased time to local failure and OS compared to tumor size &lt;3cm. Conclusion: In the current retrospective study, the use of ARBs, in combination with SBRT, was associated with a significantly increased risk of disease dissemination in early-stage NSCLC compared to SBRT alone. The findings warrant further investigations on the concurrent use of ARBs, ACEIs, and other medicines used for chronic diseases with SBRT for early-stage NSCLC.

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study.

Stereotactic body radiotherapy (SBRT) has proven to provide high rates of tumor control for patients with early-stage non-small cell lung cancer (NSCLC). We are reporting a multicenter experience of long-term clinical outcomes and adverse effect profiles of patients with medically inoperable early-stage NSCLC treated with SBRT. A total of 145 early-stage NSCLC patients underwent SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Shandong Cancer Hospital and Institute, and Shanghai Pulmonary Hospital between October 2012 and March 2019. Four-dimensional computed tomography (4D-CT) simulation was used for all patients. All received a biologically effective dose (BED; α/β=10) of 96-120 Gy with the prescribed isodose line covering >95% of the planning target volume (PTV). Survival was analyzed by the Kaplan-Meier method. Survival was estimated using the Kaplan-Meier method. The median tumor diameter was 2.2 (range, 0.5-5.2) cm. The median follow-up was of 65.6 months. Thirty-five patients (24.1%) developed disease recurrence. The rates of local, regional, and distant disease recurrence were, respectively, 5.1%, 7.4%, and 13.2% at 3 years; and 9.6%, 9.8%, and 15.8% at 5 years. Progression-free survival (PFS) rates at 3 and 5 years were 69.2% and 60.5% respectively; the overall survival (OS) rates were 78.1% and 70.1%, respectively. Five patients (3.4%) experienced grade 3 treatment-related adverse events (AEs). No patient experienced grade 4 or 5 toxicity. From our retrospective analysis with long-term follow-up in Chinese population, SBRT achieved high rate of local control (LC) and low toxicity in patients with early-stage NSCLC. This study offered robust long-term outcome data of SBRT in the Chinese population, which was very rarely reported in China before.

PO-01-050 STRUCTURAL CARDIAC CHANGES DETECTED BY MRI AFTER STEREOTACTIC BODY RADIOTHERAPY FOR TARGETS IN CLOSE PROXIMITY TO THE HEART

Stereotactic body radiation therapy (SBRT) has become a standard of care for inoperable early-stage non-small cell lung cancer and in case of pulmonary oligometastases. Recent studies indicate that incidental irradiation of the heart may be associated with an increased risk of non-cancer-related deaths. This study aims to assess and examine structural cardiac changes following peri- and myocardial SBRT using a systematic cardiac follow-up protocol including cardiac magnetic resonance (CMR) imaging. For 1485 patients treated with local-ablative SBRT from January 2014 to February 2022 at our institution, the distance between the planning target volume (PTV) and the heart was measured. Forty-eight out of 134 patients treated in close proximity (<2cm) to the heart were alive at follow-up. Of those, 20 were randomly invited to undergo a structured cardiac follow-up protocol including CMR. Ten patients consented to participate and underwent a structural follow-up protocol. Registration of CMR image data and the SBRT treatment plan was performed to examine a possible correlation between the dose delivered to the myocardium and structural cardiac changes assessed by CMR. Among the 10 participating patients, the most common primary tumors were non-small cell lung cancer (n=3) and small-cell lung cancer (n=2) (Table 1). Five patients presented with pre-SBRT cardiovascular comorbidities. Seven patients received SBRT for pulmonary or vertebral metastases and three patients for primary lung cancer with a median dose of 42.5 Gy (30.0-48.0 Gy) in 3-10 fractions. The mean heart dose (Dmean) and maximum heart dose (Dmax) were 4.9 Gy (0.7-8.4 Gy) and 36.2 Gy (8.3 – 64.1 Gy), respectively. On CMR, five patients showed myocardial alterations, such as late gadolinium enhancement and edema after a median follow-up time of 5.6 years (0.1-6.3 years) as shown in Figure 1. In patients with structural changes of the myocardium the median distance between the treated lesion and myocardium with 0.0 (0.0-1.08) cm vs. 1.4 (0.41-2.0) cm was significantly lower (p=0.015). Additionally, patients with structural changes on CMR showed significantly higher Dmax (135.4 Gy vs. 25.4 Gy, p=0.009), Dmean (4.4 Gy vs. 3.4 Gy, p=0.05). In this pilot study, patients treated with SBRT for pulmonary targets with PTV overlapping the heart showed structural changes of the myocardium in CMR. The presence of structural changes correlates with higher heart doses.

Comparison of Changes in Pulmonary Function After Stereotactic Body Radiation Therapy Versus Conventional 3-Dimensional Conformal Radiation Therapy for Stage I and IIA Non-Small Cell Lung Cancer: An Analysis of the TROG 09.02 (CHISEL) Phase 3 Trial

The [Anonymized for Review] trial compared conventional radiotherapy (CRT) with stereotactic body radiation therapy (SBRT) in patients with inoperable early-stage non-small cell lung cancer. Patients randomised to SBRT had less local failure and improved overall survival. This analysis reports differences in pulmonary function tests (PFTs) and the six-minute walk test (SMWT) between patients who received SBRT and those who received CRT. We analyzed the PFTs and SMWT of all patients recruited to the [Anonymized for Review] trial. During this trial, patients underwent serial PFTs. Linear regression models were used to compare parameters between SBRT and CRT at 3 and 12-months post-treatment. 101 patients were enrolled, 33 patients were treated with CRT, 61 with SBRT and 7 did not receive treatment. Primary tumor size was similar between arms, SBRT 25mm (SD 9mm) and CRT 28mm (SD 9mm). On regression analysis, at 3 and 12 months, there was no evidence of a difference between arms in PFT decline or distance walked in the SMWT. PTV size was significantly larger in the CRT arm, 142.79 cc (SD 61.14cc) compared to the SBRT group 46.15 cc (SD 23.39 cc). The mean Biological Equivalent Dose (BED) received by the target was significantly larger in the SBRT group 125.92 Gy (SD 21.58 Gy) compared to CRT 65.49 Gy (6.32Gy). Mean dose to the lungs - iGTV was 8.9 Gy (SD 2.34 Gy) in the CRT group and 4.37 Gy (SD 1.42 Gy) in the SBRT group. Despite the considerably higher biologically effective doses delivered to the tumor in SBRT, there was no difference in decline in respiratory function observed between the two groups.

93P A phase II study of camrelizumab plus chemotherapy in patients with medically inoperable early-stage non-small cell lung cancer

93P A phase II study of camrelizumab plus chemotherapy in patients with medically inoperable early-stage non-small cell lung cancer

Role of Stereotactic Radiation Therapy in Operable and Inoperable Early-Stage Non-small Cell Lung Cancer.

Radiation therapy is becoming an increasingly important part of non-small cell lung cancer (NSCLC) management. Approximately 60% of all cancer patients require radiation therapy (RT) as part of their treatment. For lung cancer, this number is even higher, reaching approximately 77% of all patients, from radical to palliative modalities of RT. This percentage may even be underestimated, as it may not account for the more recent use of RT in oligometastatic lung cancer patients. Thus, we can estimate that each year there will be approximately 21,890 new lung cancer patients in the USA requiring RT. These numbers are expected to continue to rise, as lung cancer radiation techniques continue to improve. There is growing interest in determining the best treatment options for early-stage NSCLC patients. There is well-established data showing the benefit of RT for inoperable patients, and more recent encouraging data even in operable patients.

Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer.

Simple SummaryThe rate of recurrence remains high for lymph node negative early-stage non-small cell lung cancer that are over 2–3 cm in size following stereotactic body radiation therapy (SBRT). This is due to the increased incidence of out-of-field failures, which warrants the addition of systemic therapy. Immune checkpoint inhibitors (ICIs), a class of immunotherapy, may induce a strong distant therapeutic effect known as the “abscopal” effect. This makes them a very suitable class of drugs to be combined with SBRT when treating early lung cancer with high-risk features, such as larger tumor size. In this review, we discuss the rationale and evidence for doing so.Stereotactic body radiation therapy (SBRT) has been widely adopted as an alternative to lobar resection in medically inoperable patients with lymph-node negative (N0) early-stage (ES) non-small cell lung cancer (NSCLC). Excellent in-field local control has been consistently achieved with SBRT in ES NSCLC ≤ 3 cm in size. However, the out-of-field control following SBRT remains suboptimal. The rate of recurrence, especially distant recurrence remains high for larger tumors. Additional systemic therapy is warranted in N0 ES NSCLC that is larger in size. Radiation has been shown to have immunomodulatory effects on cancer, which is most prominent with higher fractional doses. Strong synergistic effects are observed when immune checkpoint inhibitors (ICIs) are combined with radiation doses in SBRT’s dose range. Unlike chemotherapy, ICIs can potentiate a strong systemic response outside of the irradiated field when combined with SBRT. Together with their less toxic nature, ICIs represent a very suitable class of systemic agents to be combined with SBRT when treating ES NSCLC with high-risk features, such as larger tumor size. In this review, we describe the rationale and emerging evidence, as well as ongoing investigations in this area.

A Comparative Study of Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy Using CyberKnife and Linear Accelerator–Based Volumetric Modulated Arc Therapy

PurposeStereotactic body radiation therapy (SBRT) has become the standard of care for medically inoperable early-stage non-small cell lung cancer. We investigated 2 modalities of lung SBRT, CyberKnife (CK) and volumetric modulated arc therapy (VMAT), for differences in dosimetric parameters, tumor control, and clinical outcomes. Methods and MaterialsPatients who underwent SBRT for T1-2N0M0 non-small cell lung cancer from 2012 to 2018 were included. Dosimetric parameters for target volume coverage and organ-at-risk dose distribution were collected. Survival outcomes were evaluated using the Kaplan-Meier method with log-rank test. A multivariate Cox proportional hazards model was analyzed for local, regional, and distant tumor control; overall survival (OS) and progression-free survival; and radiation pneumonitis. ResultsTwo hundred twenty-seven patients (142 CK, 85 VMAT SBRT) met inclusion criteria. Overall, the local, regional, and distant control rates were 89.3%, 86.3%, and 87.4% at 2 years, and the OS was 67.5% and 32.8% at 2 and 5 years, respectively. VMAT delivered higher maximum doses to the gross tumor volume and planning target volume and had a lower lung and heart V5. Although there was no difference in local or distant failure, progression-free survival, or OS, VMAT was associated with superior freedom from regional failure (adjusted hazard ratio, 0.26; P = .045). With no difference between treatment modalities, 11.9% of patients developed grade 1 to 2 radiation pneumonitis. There were no grade 3+ events of radiation pneumonitis. ConclusionsThis study revealed that VMAT and CK provided comparable local and distant control and survival outcomes; however, VMAT exhibited better regional control. Further study in this regard is imperative.

Comparison of stereotactic body radiotherapy and radiofrequency ablation for early-stage non-small cell lung cancer: a systematic review and meta-analysis.

BackgroundStereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are recommended for patients with inoperable early-stage non-small cell lung cancer (NSCLC), with both offering promising results. However, it is largely unknown which of these two treatment modalities provides superior benefits for patients. Therefore, this systematic review and meta-analysis compared clinical outcomes and safety between SBRT and RFA in patients with inoperable early-stage NSCLC.MethodsEligible studies published between 2001 and 2020 were obtained through a comprehensive search of the PubMed, Medline, Embase, and Cochrane Library databases. Original English-language studies on the treatment of early-stage NSCLC with SBRT or RFA were included. Local control (LC) rates, overall survival (OS) rates, and adverse events were obtained by pooled analyses.ResultsEighty-seven SBRT studies (12,811 patients) and 18 RFA studies (1,535 patients) met the eligibility criteria. For SBRT, the LC rates (with 95% confidence intervals) at 1, 2, 3, and 5 years were 98% (97–98%), 95% (95–96%), 92% (91–93%), and 92% (91–93%), respectively, which were significantly higher than those for RFA [75% (69–82%), 31% (22–39%), 67% (58–76%), and 41% (30–52%), respectively] (P<0.01). There were no significant differences in short-term OS between SBRT and RFA [1-year OS rate: 87% (86–88%) versus 89% (88–91%), P=0.07; 2-year OS rate: 71% (69–72%) versus 69% (64–74%), P=0.42]. Regarding long-term OS, the 3- and 5-year OS rates for SBRT were 58% (56–59%) and 39% (37–40%), respectively, which were significantly (P<0.01) superior to those for RFA [48% (45–51%) and 21% (19–23%), respectively]. The most common complication of SBRT was radiation pneumonitis (grade ≥2), making up 9.1% of patients treated with SBRT, while pneumothorax was the most common complication of RFA, making up 27.2% of patients treated with RFA.DiscussionCompared with RFA, SBRT has superior LC and long-term OS rates but similar short-term OS rates. Prospective randomized trials with large sample sizes comparing the efficacy of SBRT and RFA are warranted.

Tumor Control and Survival Outcomes Based on Maximum Standardized Uptake Value on FDG-PET/CT in T1-2 NSCLC Treated With SBRT

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is standard of care in medically inoperable early-stage non-small cell lung cancer (NSCLC). Assessment of maximum standardized uptake value (SUVmax) on FDG-PET/CT before and after SBRT may stratify tumor control and survival outcomes. <h3>Materials/Methods</h3> Retrospective chart review identified patients with T1-2N0M0 NSCLC who were only treated with SBRT between 2012 and 2019. Pretreatment SUVmax and percent change in SUVmax at 3 and 6 months following SBRT were assessed as independent predictors of local control (LC), regional failure-free survival (RFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS). Receiver operator characteristic (ROC) analysis yielded optimal cut points for comparison. Survival analyses were performed with Kaplan-Meier estimates with log rank testing, and Cox proportional hazards models including age, sex, T stage, histology, and performance status. <h3>Results</h3> 71 (43.6%) out of 163 patients underwent repeat PET/CT within 6 months of SBRT completion. Median follow-up was 19 months (range 1 – 94 months). For the whole cohort, 1-year and 2-year LC, PFS, and OS were 95.0% and 80.3%, 75.9% and 47.7%, and 87.1% and 67.0%, respectively. For DFFS, pretreatment SUVmax greater than 4 had an aHR of 3.33 (95% CI 1.42 – 7.84, <i>P</i> = 0.006). Pre-SBRT SUVmax over 12.3 had an aHR of 2.80 (95% CI 1.3 – 6.2, <i>P</i> = 0.011) for PFS, and a cut point of 12.6 had an aHR of 3.00 (95% CI 1.6 – 5.8, <i>P</i> = 0.003) for OS. Pretreatment SUVmax did not significantly predict LC or RFFS. At 3 months following SBRT, an SUVmax decrease of at least 45% was associated with improved LC (aHR = 0.15, 95% CI 0.02 – 0.91, <i>P</i> = 0.018). A 6-month SUVmax decrease of more than 53% was associated with better LC (<i>P</i> = 0.038), and a decrease over 11% was associated with improved RFFS (aHR = 0.12, 95% CI 0.02 – 0.96, <i>P</i> = 0.046). Change in SUVmax was not significantly associated with DFFS, PFS, or OS at either time point. No factors other than performance status for PFS and OS were significant. <h3>Conclusion</h3> At 3 and 6 months following SBRT, cut points for percentage change in SUVmax can stratify risk of local recurrence and possibly regional recurrence. Pretreatment SUVmax cutoffs can predict distant failure, progression-free survival, and overall survival in early-stage NSCLC.

Safety and Effectiveness of Definitive Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer Among Older Patients: Does Frailty Matter?

Older patients with inoperable early-stage non-small cell lung cancer (NSCLC) are mainly treated with definitive stereotactic body radiation therapy (SBRT) and represent an especially frail patient subset with unique challenges that may impact treatment tolerability and survival outcomes. The Electronic Rapid Fitness Assessment (eRFA) is a validated web-based comprehensive geriatrics assessment used for measuring frailty. We report our initial experience prospectively applying the eRFA to inoperable NSCLC patients treated with SBRT.We collected baseline pretreatment eRFAs from early-stage (cT1a-T3N0) NSCLC patients aged 60 years and older receiving definitive SBRT (48-60 Gy in 3-8 fractions) from June 2019 to December 2020. Patient demographics and Charlson comorbidity index (CCI) were assessed. Geriatric assessment domains measured by the eRFA include functional status, social and emotional wellbeing, cognitive function, fall risk, nutritional status and polypharmacy. Our primary endpoint was the association between pretreatment eRFA scores and physician-assessed SBRT toxicity per CTCAE v5.0. Secondary outcomes included overall survival (OS), local control (LC) and distant metastasis-free survival (DMFS). Survivals were assessed using the Kaplan-Meier method. Univariate and multivariate logistic regression and Cox proportional hazards modeling were performed.We enrolled 80 patients (median age: 78) with 88 primary tumors. We observed high baseline rates of geriatric vulnerabilities with a median of four eRFA impairments (IQR: 2-6). More than 50% of patients reported limited social activity, poor social support, depression, and dependency for activities of daily living, and more than 40% reported significant distress. Karnofsky Performance Status was ≤80 in 38% of patients. Cumulative toxicity rates after SBRT were 13% and 1% for Grade II and III toxicities, respectively. After a median follow-up of 12.9 months, 1-year OS, LC and DMFS rates were 96%, 92% and 97%, respectively. Comprehensive eRFA scores were significantly associated with increased likelihood of developing posttreatment toxicities on univariate analysis (LR: 2.20, P < 0.001), as were CCI scores (LR: 1.47, P = 0.025). Due to co-correlation of CCI and eRFA multivariate analysis was not performed. eRFA scores did not predict overall survival.In this cohort, definitive SBRT was well-tolerated with excellent oncologic outcomes despite high observed rates of baseline geriatric vulnerabilities. Frailty assessed by the eRFA score was associated with higher cumulative toxicity rate. Future studies should further explore such relationships and assess interventions aimed at minimizing toxicity for patients with higher degree of geriatric frailty.

Primary Tumor Control in Stereotactic Ablative Radiation Therapy for Large (≥ 5 cm) Non-Small Cell Lung Cancer: Does It Last?

<h3>Purpose/Objective(s)</h3> While prospective trials have established stereotactic body radiation therapy (SBRT) as standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), these studies excluded patients with tumors larger than 5 cm. Since these patients have few treatment options and conservative management is associated with significant morbidity, many clinicians utilize SBRT if dosimetric constraints can be met. The purpose of this study is to determine the rate of primary tumor failure (PTF) after SBRT for NSCLC with primaries ≥ 5cm. <h3>Materials/Methods</h3> We performed a retrospective review of all patients with NSCLC and large primary tumors (≥ 5 cm in maximum dimension) treated at our institution using SBRT from 2010 – 2018. Patients with nodal or distant disease were included, but only evaluated for toxicity and PTF. Treatment failures were captured by review of imaging, pathology, and clinical notes. PTF was defined as disease recurrence in or at the margin of the primary tumor volume (PTV) and was measured from end of SBRT to PTF. Patients without PTF were censored at last follow up or death. The Kaplan-Meier method was used to estimate event-time probabilities for PTF. Predictors of PTF were analyzed using log rank tests between groups and a parsimonious multivariate Cox multivariate model. <h3>Results</h3> A total of 145 patients were identified. Median age was 78 years (Interquartile rage [IQR] 72 -84). Evidence of regional disease was present in 5 (3%) patients and metastatic disease in 14 (10%). Median tumor diameter was 5.75 cm (IQR 5.25 – 6.43) and tumor volume was 37.9 cm³ (IQR 25.4 – 53.6). The most common SBRT regimen was 48 Gy in 4 fractions (68 patients). Median BED10 was 105.6 (IQR 105.6-151.2). With a median follow up of 21 months (IQR 9 – 32), PTF at 1, 2, and 3 years was 10.6% (95% Confidence Interval [CI] 5.1 – 16.1), 17.0% (95% CI 9.9 – 24.1), and 22.0% (95% CI 13.4 – 30.6). On univariate analysis, factors associated with PTF included lobe involved (<i>P</i> = 0.01), maximum tumor diameter > 5.75 cm (<i>P</i> < 0.01), four-fraction SBRT (<i>P</i> = 0.01), and BED10 ≤ 105.6 (<i>P</i> = 0.03). On multivariate analysis, tumor diameter > 5.75cm (HR 3.28, 95% CI 1.44 – 7.46) and four-fraction SBRT (HR 3.20, 95% CI 1.38 – 7.41) remained significant. In patients with node negative and non-metastatic disease, 2-year disease free survival and overall survival were 62.1% (95% CI 51.6 – 70.8) and 49.3% (95% CI 41.5 – 59.9). Acute toxicity was absent in 106 (73%) patients and no patients experienced grade 3 or higher acute toxicity. Maximum late toxicity was Grade 1-2 in 96 (66%) patients (predominantly asymptomatic radiation pneumonitis) and Grade 3 or higher in five (3%) patients including one patient with a contralateral pneumonectomy who experienced fatal radiation pneumonitis. <h3>Conclusion</h3> SBRT for medically inoperable NSCLC ≥ 5cm results in acceptable tumor control and toxicity, although the rate of PTF increases with longer follow up. PTF appears to be higher in patients with tumors > 5.75 cm in diameter and those receiving 48 Gy in 4 fractions.

P05.05 Impact of Lung Stereotactic Body Radiotherapy on Pulmonary Function Test – Experience from Tertiary Cancer Centre in India

Stereotactic body radiotherapy (SBRT) has proven to be an effective modality for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC) and pulmonary metastases. However, the concern remains of its effect on pulmonary function test parameters especially in patients with chronic obstructive pulmonary disease (COPD).

P05.03 Comparison of Stereotactic Body Radiotherapy and Radiofrequency Ablation for Early-Stage NSCLC: A Systemic Review and Pooled Analysis

Both stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) offer promising therapeutic options for patients with inoperable early-stage non-small cell lung cancer (NSCLC), but it is unclear which treatment would provide superior benefits for patients. In this systematic review and pooled analysis, we compare clinical outcomes and safety between SBRT and RFA for patients with inoperable early-stage NSCLC.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

Prognostic value of SUVmax on FDG-PET/CT before and after stereotactic body radiotherapy (SBRT) on recurrence and survival in early-stage non-small cell lung cancer (NSCLC).

8539 Background: Stereotactic body radiotherapy (SBRT) is the standard of care in medically inoperable early-stage non-small cell lung cancer (NSCLC). Assessment of FDG-PET/CT before and after SBRT may stratify risk of disease recurrence and survival outcomes. Methods: Patients with T1-2N0M0 NSCLC who underwent PET/CT prior to SBRT (50-60 Gy over 3-5 fractions) between 2012 and 2019 were retrospectively identified. Pre-SBRT SUVmax and change in SUVmax at 3 and 6 months after SBRT were assessed as predictors of local control (LC), progression-free survival (PFS), and overall survival (OS). Optimal cutoff points for comparison were determined by receiver operator characteristic (ROC) analysis. Survival analyses were performed with Kaplan-Meier estimates with log rank testing, and Cox proportional hazards models including age, sex, T stage, histology, and performance status. Results: Out of 163 patients identified, 71 (43.6%) underwent repeat PET/CT within 6 months of SBRT completion. Median follow-up was 19 months (range 1 – 94 months). For the whole cohort, 1-year and 2-year LC, PFS, and OS were 95.0% and 80.3%, 75.9% and 47.7%, and 87.1% and 67.0%, respectively. Pre-SBRT SUVmax greater than 12.3 had an aHR of 2.80 (95% CI 1.3 – 6.2, p = 0.011) for PFS. A cutpoint of 12.6 for pre-SBRT SUVmax had an aHR of 3.00 (95% CI 1.6 – 5.8, p = 0.003) for OS. Pre-SBRT SUVmax did not significantly predict LC. A 3-month SUVmax decrease of at least 45% was associated with improved LC (aHR = 0.15, 95% CI 0.02 – 0.91, p = 0.018). At 6 months following SBRT, a cutoff point of a 53% decrease in SUVmax was associated with better LC (p = 0.038). Change in SUVmax was not significantly associated with PFS or OS at either time point. Performance status significantly predicted PFS and OS in all models. No other factors were significant. Conclusions: Pre-treatment SUVmax cutoffs can predict PFS and OS in early-stage NSCLC. At both the 3- and 6-month time points following SBRT, cutoff values for change in SUVmax can stratify risk of local recurrence.[Table: see text]