We sought to quantify contribution of radiomics and SUVmax at PET/CT to predict clinical outcome in lung cancer patients treated with stereotactic body radiotherapy (SBRT). 150 patients with 172 lung ...cancers, who underwent SBRT were retrospectively included. Radiomics were applied on PET/CT. Principal components (PC) for 42 CT and PET-derived features were examined to determine which ones accounted for most of variability. Survival analysis quantified ability of radiomics and SUVmax to predict outcome. PCs including homogeneity, size, maximum intensity, mean and median gray level, standard deviation, entropy, kurtosis, skewness, morphology and asymmetry were included in prediction models for regional control (RC) PC4-HR:0.38, p = 0.02, distant control (DC) PC4-HR:0.51, p = 0.02 and PC1-HR:1.12, p = 0.01, recurrence free probability (RFP) PC1-HR:1.08, p = 0.04, disease specific survival (DSS) PC2-HR:1.34, p = 0.03 and PC3-HR:0.64, p = 0.02 and overall survival (OS) PC4-HR:0.45, p = 0.004 and PC3-HR:0.74, p = 0.02. In combined analysis with SUVmax, PC1 lost predictive ability over SUVmax for RFP HR:1.1, p = 0.04 and DC HR:1.13, p = 0.002, while PC4 remained predictive of DC independent of SUVmax HR:0.5, p = 0.02. Radiomics remained the only predictors of OS, DSS and RC. Neither SUVmax nor radiomics predicted recurrence free survival. Radiomics on PET/CT provided complementary information for prediction of control and survival in SBRT-treated lung cancer patients.
Randomised controlled trials comparing surgery with non-surgical treatment for cancer have been notoriously difficult to complete, owing to challenges in both equipoise and preference in patients and ...providers alike.1 Debate on the relative merit of stereotactic ablative radiotherapy (SABR) versus surgery for early-stage non-small-cell lung cancer (NSCLC) is no exception. Prospective randomised controlled trials designed to identify a so-called winner between surgery and SABR have not been able to accrue, and the pooled analysis from the prematurely closed original STARS and ROSEL studies has been a lightning rod for discussion among thoracic oncologists.2 Even with other comparative effectiveness studies attempting to adjust for confounding, inherent limitations engender polarising opinions.3 In The Lancet Oncology, Joe Chang and colleagues present the results of the new revised STARS cohort of an additional 80 patients with medically operable early-stage NSCLC treated with SABR.4 The authors should be congratulated on the robust study conduct. Ultra-central tumours were not included; both lobectomy and SABR are challenging in this cohort and further comparative data are required.9 Furthermore, biomarker data were not available in STARS, and have implications for both prognostication and salvage therapies.10 Until randomised controlled trials are completed, for younger, fitter patients presenting with stage IA NSCLC, it seems that there are two outstanding treatment options available for long-term survival.
Although stereotactic radiation has frequently supplanted whole-brain radiation therapy (WBRT) in treating patients with multiple brain metastases, the role of surgery for these patients remains ...unresolved. No randomized trials have compared surgical resection with postoperative stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) to SRS/SRT alone. Previous studies addressing surgery for patients with multiple brain metastases are often limited by small sample sizes, a lack of appropriate comparison groups, or a focus on patients treated before recent advances in targeted therapy and immunotherapy. We compared outcomes in patients with multiple brain metastases treated with surgical resection and postoperative SRS/SRT to those treated with SRS/SRT alone.
We studied 734 patients with multiple newly diagnosed brain metastases (surgery with SRS/SRT, n = 228; SRS/SRT alone, n = 506) from 2011 to 2022 in a retrospective, single-institution cohort. Patients who received upfront whole-brain radiotherapy were excluded. Cox proportional hazards models were constructed for overall survival and additional intracranial outcomes.
After adjustment for potential confounders, surgery with postoperative SRS/SRT was associated with decreased all-cause mortality compared with SRS/SRT alone (hazard ratio HR: 0.67, 95% CI 0.50-0.89, P = 5.56 × 10 -3 ). The association between surgical resection and overall survival was replicated in a subset of the cohort after cardinality matching (HR: 0.64, 95% CI 0.46-0.88, P = 6.68 × 10 -3 ). Patients with melanoma benefited significantly less from surgical resection compared with patients with other tumor types, most notably non-small-cell lung cancer. Compared with definitive SRS/SRT, cavity SRS/SRT was associated with a significantly reduced risk of both symptomatic radiation necrosis (HR: 0.22, 95% CI 0.08-0.59, P = 2.70 × 10 -3 ) and radiographic radiation necrosis (HR: 0.23, 95% CI 0.09-0.57, P = 1.43 × 10 -3 ) in multivariable models.
In patients with multiple brain metastases, surgical resection before SRS/SRT is associated with reduced mortality and radiation necrosis. Prospective studies may further delineate patient populations that benefit from aggressive local, brain-directed treatment even with significant intracranial disease burden.
•LAD coronary artery V15 Gy (LADV15), but not mean heart dose, predicted MACE post-radiotherapy.•Coronary heart disease, Hypertension, and Logarithmic LADV15 (CHyLL model) predicted MACE.•High risk ...patients (CHyLL>5) had >20% 4-year MACE rates; low risk (CHyLL≤5) patients had <10% rates.•Calculated LADV15 constraint for patients without CHD or hypertension was 28.3% to remain low risk.•Calculated LADV15 low risk constraint was 11.3% for patients without CHD but with hypertension.
In patients with locally advanced non-small cell lung cancer (LA-NSCLC) post-radiotherapy, mean heart dose (MHD) and the percent of left anterior descending (LAD) coronary artery receiving ≥15 Gy (LADV15) are associated with major adverse cardiac events (MACE). We developed a MACE prediction model in this population.
Total 701 patients with LA-NSCLC treated with curative-intent radiotherapy reviewed, split by diagnosis date into “development” (n = 500) and later (n = 201) “test” cohorts. Development patients were analyzed using a multivariable Cox-proportional hazard model with backward elimination scheme (Bonferroni-adjusted α = 0.025). Potential predictors were selected a priori: age, coronary heart disease (CHD), Framingham Risk, hypertension, MHD, LADV15, intensity modulated radiotherapy use, and CHD and LADV15 interaction (CHD:LADV15). Cardiac doses as quadratic, square root, and logarithmic (lnX + 1) forms were explored. Models were internally validated with bootstrapping.
Final model incorporated CHD, Hypertension, Logarithmic LADV15, and CHD*lnLADV15 + 1 (CHyLL; β coefficients: 5.51, 1.28, 1.48, −1.36; all p < 0.025; bootstrapping c-index: 0.80; test cohort c-index: 0.76). Possible risk score range: 0–8.11. MACE incidence was 6.8% and 23.6% at 48 months (p = 0.041), and survival rates were 51.6% and 35.0% (p = 0.099), in the low-risk (score <5.00) and high-risk (score ≥5) test groups, respectively. Using the model, calculated LADV15 constraints for patients without CHD were 11.3% and 28.3% for those with and without hypertension, respectively, to remain low-risk.
Pre-existing CHD, hypertension, and LADV15 were important factors in predicting MACE after radiotherapy. CHyLL has the potential to estimate personalized LADV15 constraints based on cardiac risk factors and acceptable MACE thresholds.
Radiotherapy (RT) and chemotherapy continue to be widely utilized in small cell lung cancer (SCLC) management. In most limited stage (LS)-SCLC cases, the standard initial therapy remains concurrent ...chemoradiotherapy (CRT), typically with an etoposide and platinum-based regimen. Hyperfractionated twice daily (BID) RT remains the standard of care, though conventional daily (QD) RT is now a viable alternative supported by randomized evidence. In LS-SCLC patients who experienced good response to CRT, prophylactic cranial irradiation (PCI) remains the standard of care. Brain imaging, ideally with MRI, should be performed prior to PCI to screen for clinically apparent brain metastases that may require a higher dose of cranial irradiation. Platinum doublet chemotherapy alone is the historic standard initial therapy in extensive stage (ES)-SCLC. Addition of immunotherapy such as atezolizumab and durvalumab to chemotherapy is now recommended after their benefits were demonstrated in recent trials. In patients with response to chemotherapy, consolidation thoracic RT and PCI could be considered, though with caveats. Emergence of hippocampal avoidance cranial irradiation and SRS in SCLC patients may supplant whole cranial irradiation as future standards of care. Incorporation of novel systemic therapies such as immunotherapies has changed the treatment paradigm and overall outlook of patients with SCLC. This narrative review summarizes the current state, ongoing trials, and future directions of radiotherapy in management of SCLC.Radiotherapy (RT) and chemotherapy continue to be widely utilized in small cell lung cancer (SCLC) management. In most limited stage (LS)-SCLC cases, the standard initial therapy remains concurrent chemoradiotherapy (CRT), typically with an etoposide and platinum-based regimen. Hyperfractionated twice daily (BID) RT remains the standard of care, though conventional daily (QD) RT is now a viable alternative supported by randomized evidence. In LS-SCLC patients who experienced good response to CRT, prophylactic cranial irradiation (PCI) remains the standard of care. Brain imaging, ideally with MRI, should be performed prior to PCI to screen for clinically apparent brain metastases that may require a higher dose of cranial irradiation. Platinum doublet chemotherapy alone is the historic standard initial therapy in extensive stage (ES)-SCLC. Addition of immunotherapy such as atezolizumab and durvalumab to chemotherapy is now recommended after their benefits were demonstrated in recent trials. In patients with response to chemotherapy, consolidation thoracic RT and PCI could be considered, though with caveats. Emergence of hippocampal avoidance cranial irradiation and SRS in SCLC patients may supplant whole cranial irradiation as future standards of care. Incorporation of novel systemic therapies such as immunotherapies has changed the treatment paradigm and overall outlook of patients with SCLC. This narrative review summarizes the current state, ongoing trials, and future directions of radiotherapy in management of SCLC.
Background
In Ontario, Canada, patient‐reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV ...non‐small cell lung cancer (NSCLC) is associated with substantial disease and treatment‐related morbidity, this province‐wide study investigated moderate to severe symptom burden in this population.
Materials and Methods
ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance.
Results
Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well‐being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well‐being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior.
Conclusion
This province‐wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments.
Implications for Practice
In this largest study of lung cancer patient‐reported outcomes (PROs), stage IV non‐small cell lung cancer patients had worse moderate‐to‐severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate‐to‐severe symptoms peaked early and remained high during the first year of follow‐up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in‐person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.
Reporting a study in Canada, this article analyzes utilization of patient‐reported outcomes and symptom burden among patients with stage IV non‐small cell lung cancer, providing a basis for the development of strategies to address gaps in symptom management in this patient population.
•26 central (19 ultra-central) oligo-metastases were treated by isotoxic 5-fraction SMART•Adaptive replanning was indicated in 96% to meet OAR metrics and/or target coverage•With median follow-up of ...17 months, 1-year local control rate was 96 %•Limited toxicity was observed with 4 % acute G3 and no late G2 + toxicity•Isotoxic SMART may widen the therapeutic window for high-risk thoracic tumors
Central/ultra-central thoracic tumors are challenging to treat with stereotactic radiotherapy due potential high-grade toxicity. Stereotactic MR-guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath-hold gating and real-time MR-imaging as well as the option for daily online adaptive replanning to account for changes in target and/or organ-at-risk (OAR) location.
26 central (19 ultra-central) thoracic oligoprogressive/oligometastatic tumors treated with isotoxic (OAR constraints-driven) 5-fraction SMART (median 50 Gy, range 35–60) between 10/2019–10/2022 were reviewed. Central tumor was defined as tumor within or touching 2 cm around proximal tracheobronchial tree (PBT) or adjacent to mediastinal/pericardial pleura. Ultra-central was defined as tumor abutting the PBT, esophagus, or great vessel. Hard OAR constraints observed were ≤ 0.03 cc for PBT V40, great vessel V52.5, and esophagus V35. Local failure was defined as tumor progression/recurrence within the planning target volume.
Tumor abutted the PBT in 31 %, esophagus in 31 %, great vessel in 65 %, and heart in 42 % of cases. 96 % of fractions were treated with reoptimized plan, necessary to meet OAR constraints (80 %) and/or target coverage (20 %). Median follow-up was 19 months (27 months among surviving patients). Local control (LC) was 96 % at 1-year and 90 % at 2-years (total 2/26 local failure). 23 % had G2 acute toxicities (esophagitis, dysphagia, anorexia, nausea) and one (4 %) had G3 acute radiation dermatitis. There were no G4-5 acute toxicities. There was no symptomatic pneumonitis and no G2 + late toxicities.
Isotoxic 5-fraction SMART resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk oligoprogressive/oligometastatic thoracic tumors.
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