Beyond conventional bounds: Surpassing system limits for stereotactic ablative (SAbR) lung radiotherapy using CBCT-based adaptive planning system.

PURPOSE: Online adaptive radiotherapy relies on a high degree of automation to enable rapid planning procedures. The Varian Ethos intelligent optimization engine (IOE) was originally designed for conventional treatments so it is crucial to provide clear guidance for lung SAbR plans. This study investigates using the Ethos IOE together with adaptive-specific optimization tuning structures we designed and templated within Ethos to mitigate inter-planner variability in meeting RTOG metrics for both online-adaptive and offline SAbR plans. METHODS: We developed a planning strategy to automate the generation of tuning structures and optimization. This was validated by retrospective analysis of 35 lung SAbR cases (total 105 fractions) treated on Ethos. The effectiveness of our planning strategy was evaluated by comparing plan quality with-and-without auto-generated tuning structures. Internal target volume (ITV) contour was compared between that drawn from CT simulation and from cone-beam CT (CBCT) at time of treatment to verify CBCT image quality and treatment effectiveness. Planning strategy robustness for lung SAbR was quantified by frequency of plans meeting reference plan RTOG constraints. RESULTS: Our planning strategy creates a gradient within the ITV with maximum dose in the core and improves intermediate dose conformality on average by 2%. ITV size showed no significant difference between those contoured from CT simulation and first fraction, and also trended towards decreasing over course of treatment. Compared to non-adaptive plans, adaptive plans better meet reference plan goals (37% vs. 100% PTV coverage compliance, for scheduled and adapted plans) while improving plan quality (improved GI (gradient index) by 3.8%, CI (conformity index) by 1.7%). CONCLUSION: We developed a robust and readily shareable planning strategy for the treatment of adaptive lung SAbR on the Ethos system. We validated that automatic online plan re-optimization along with the formulated adaptive tuning structures can ensure consistent plan quality. With the proposed planning strategy, highly ablative treatments are feasible on Ethos.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiation Therapy for Locally Advanced Lung Cancer.

PURPOSE: Real-time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiation therapy (o-ART) on the ETHOS system with image guided radiation therapy delivery on a Halcyon unit for conventional fractionated radiation therapy of locally advanced lung cancer (LALC). METHODS AND MATERIALS: We analyzed 26 patients with LALC treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real-world clinic. Target coverage and organ at risk (OAR) doses were compared between adaptive plans (ADP) and nonadaptive scheduled plans (SCH). Planning robustness was evaluated by the frequency of preplanning goals achieved in ADP plans, stratified by tumor volume change. RESULTS: The AOD workflow was achievable within 30 minutes for most radiation fractions. Over the course of therapy, we observed an average 26.6% ± 23.3% reduction in internal target volume (ITV). Despite these changes, with o-ART, ITV and planning target volume (PTV) coverage (V100%) was 99.2% and 93.9% for all members of the cohort, respectively. This represented a 2.9% and 6.8% improvement over nonadaptive plans (P < .05), respectively. For tumors that grew >10%, V100% was 93.1% for o-ART and 76.4% for nonadaptive plans, representing a median 17.2% improvement in the PTV coverage (P < .05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in nonadaptive plans, this figure was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in the heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. CONCLUSIONS: The AOD workflow is efficient and robust in responding to anatomic changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiation therapy.

American Radium Society Appropriate Use Criteria for Unresectable Locally Advanced Non-Small Cell Lung Cancer.

Importance: The treatment of locally advanced non-small cell lung cancer (LA-NSCLC) has been informed by more than 5 decades of clinical trials and other relevant literature. However, controversies remain regarding the application of various radiation and systemic therapies in commonly encountered clinical scenarios. Objective: To develop case-referenced consensus and evidence-based guidelines to inform clinical practice in unresectable LA-NSCLC. Evidence Review: The American Radium Society (ARS) Appropriate Use Criteria (AUC) Thoracic Committee guideline is an evidence-based consensus document assessing various clinical scenarios associated with LA-NSCLC. A systematic review of the literature with evidence ratings was conducted to inform the appropriateness of treatment recommendations by the ARS AUC Thoracic Committee for the management of unresectable LA-NSCLC. Findings: Treatment appropriateness of a variety of LA-NSCLC scenarios was assessed by a consensus-based modified Delphi approach using a range of 3 points to 9 points to denote consensus agreement. Committee recommendations were vetted by the ARS AUC Executive Committee and a 2-week public comment period before official approval and adoption. Standard of care management of good prognosis LA-NSCLC consists of combined concurrent radical (60-70 Gy) platinum-based chemoradiation followed by consolidation durvalumab immunotherapy (for patients without progression). Planning and delivery of locally advanced lung cancer radiotherapy usually should be performed using intensity-modulated radiotherapy techniques. A variety of palliative and radical fractionation schedules are available to treat patients with poor performance and/or pulmonary status. The salvage therapy for a local recurrence after successful primary management is complex and likely requires both multidisciplinary input and shared decision-making with the patient. Conclusions and Relevance: Evidence-based guidance on the management of various unresectable LA-NSCLC scenarios is provided by the ARS AUC to optimize multidisciplinary patient care for this challenging patient population.

The Emerging Role of Immunotherapy in Resectable Non-Small Cell Lung Cancer.

BACKGROUND: Despite surgical resection, long-term survival of patients with resectable non-small cell lung cancer (NSCLC) remains poor. Adjuvant chemotherapy, the standard of care for locally advanced NSCLC, provides a marginal 5.4% benefit in survival. Immune checkpoint inhibitors (ICIs) have shown a significant survival benefit in some patients with advanced NSCLC and are being evaluated for perioperative use in resectable NSCLC. METHODS: We conducted a literature search using the PubMed online database to identify clinical trials of immunotherapy in resectable NSCLC and studies analyzing biomarkers and immune priming strategies. RESULTS: Building on previous phase I and II trials, randomized phase III trials have shown efficacy of neoadjuvant nivolumab, perioperative pembrolizumab, adjuvant atezolizumab, and adjuvant pembrolizumab in the treatment of NSCLC with improvement of event-free/disease-free survival of 24% to 42%, leading to United States Food and Drug Administration approval of these drugs in the treatment of resectable NSCLC. Three additional phase III trials have also recently reported the use of immunotherapy both before and after surgery, with pathologic complete response rates of 17% to 25%, significantly better than chemotherapy alone. Perioperative ICI therapy has comparable perioperative morbidity to chemotherapy alone and does not impair surgical outcomes. CONCLUSIONS: Perioperative immunotherapy, in combination with chemotherapy, is safe and improves outcomes in patients with resectable NSCLC. Questions regarding patient selection, the need for adjuvant ICI therapy after neoadjuvant chemoimmunotherapy, and the duration of perioperative immunotherapy remain to be answered by future trials.

Disparities in Stage at Presentation Among Hispanic and Latinx Patients With Non-Small-Cell Lung Cancer in the United States.

PURPOSE: Hispanic and Latinx people in the United States are the fastest-growing ethnic group. However, previous studies in non-small-cell lung cancer (NSCLC) often analyze these diverse communities in aggregate. We aimed to identify differences in NSCLC stage at diagnosis in the US population, focusing on disaggregated Hispanic/Latinx individuals. METHODS: Data from the National Cancer Database from 2004 to 2018 identified patients with primary NSCLC. Individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression adjusting for age, facility type, income, educational attainment, comorbidity index, insurance, and year of diagnosis was used to create adjusted odds ratios (aORs), with higher odds representing diagnosis at later-stage NSCLC. RESULTS: Of 1,565,159 patients with NSCLC, 46,616 were Hispanic/Latinx (3.0%). When analyzed in the setting of race and ethnicity, Hispanic patients were more likely to be diagnosed with metastatic disease compared with non-Hispanic White (NHW) patients: 47.0% for Hispanic Black, 46.0% Hispanic White, and 44.3% of Hispanic other patients versus 39.1% of non-Hispanic White patients (P < .001 for all). By country of origin, 51.4% of Mexican, 41.7% of Puerto Rican, 44.6% of Cuban, 50.8% of South or Central American, 48.4% of Dominican, and 45.6% of other Hispanic patients were diagnosed with metastatic disease, compared with 39.1% of NHWs. Conversely, 20.2% of Mexican, 26.9% of Puerto Rican, 24.2% of Cuban, 22.5% of South or Central American, 23.7% of Dominican, and 24.5% of other Hispanic patients were diagnosed with stage I disease, compared with 30.0% of NHWs. All Hispanic groups were more likely to present with later-stage NSCLC than NHW patients (greatest odds for Mexican patients, aOR, 1.44; P < .001). CONCLUSION: Hispanic/Latinx patients with non-small-cell lung cancer were more likely to be diagnosed with advanced disease compared with NHWs. Disparities persisted upon disaggregation by both race and country of origin, with over half of Mexican patients with metastatic disease at diagnosis. Disparities among Hispanic/Latinx groups by race and by country of origin highlight the shortcomings of treating these groups as a monolith and underscore the need for disaggregated research and targeted interventions.

Impact of Pretreatment Weight Loss on Radiotherapy Utilization and Clinical Outcomes in Non-Small Cell Lung Cancer.

BACKGROUND: Cancer cachexia is a syndrome of unintentional weight loss resulting in progressive functional impairment. Knowledge of radiation therapy utilization in patients with cancer cachexia is limited. We evaluated the use of curative and palliative-intent radiation for the management of patients with non-small cell lung cancer (NSCLC) with cachexia to determine whether tumor-directed therapy affected cachexia-associated outcomes. METHODS: Using an Institutional Tumor Registry, we evaluated all patients with stages of NSCLC treated at a tertiary care system from 2006 to 2013. We adopted the international consensus definition for cachexia, with staging designated by the registry and positron emission tomography. Radiotherapy delivery and intent were retrospectively assessed. RESULTS: In total, 1330 patients with NSCLC were analyzed. Curative-intent radiotherapy was utilized equally between patients with cachexia and non-cachexia with stages I to III NSCLC. Conversely, significantly more patients with stage IV disease and cachexia received palliative radiotherapy versus those without (74% vs 63%, P = 0.006). Cachexia-associated survival was unchanged irrespective of tumor-directed radiation therapy with curative or palliative intent. In fact, pretreatment cachexia was associated with reduced survival for patients with stage III NSCLC receiving curative-intent radiotherapy (median survival = 23.9 vs 15.0 mo, P = 0.009). Finally, multivariate analysis identified pretreatment cachexia as an independent variable associated with worsened survival (hazard ratio = 1.31, CI: 1.14,1.52). CONCLUSION: Patients with advanced NSCLC with cachexia received more palliative-intent radiation than those without weight loss. Tumor-directed therapy in either a curative or palliative approach failed to alter cachexia patient survival across all stages of the disease. These findings offer critical information on the appropriate utilization of radiation in the management of patients with NSCLC with cachexia.

BIOGUIDE-X: A First-in-Human Study of the Performance of Positron Emission Tomography-Guided Radiation Therapy.

PURPOSE: Positron emission tomography (PET)-guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fluorodeoxyglucose (FDG) dose for PET-guided therapy and (2) confirm that the emulated dose distribution was consistent with a physician-approved radiation therapy plan. METHODS AND MATERIALS: This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET-guided therapy. For cohort II, PET imaging data were collected on the X1 system before the first and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET-guided therapy dose distributions were modeled on the patient's computed tomography anatomy using the collected PET data at each fraction as input to an "emulated delivery" and compared with the physician-approved plan. RESULTS: Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the first injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET-guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose-volume histogram score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations. CONCLUSIONS: PET-guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fiducial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics.

Evaluation of fan-beam kilovoltage computed tomography image quality on a novel biological-guided radiotherapy platform.

Background and Purpose: A recently developed biology-guided radiotherapy platform, equipped with positron emission tomography (PET) and computed tomography (CT), provides both anatomical and functional image guidance for radiotherapy. This study aimed to characterize performance of the kilovoltage CT (kVCT) system on this platform using standard quality metrics measured on phantom and patient images, using CT simulator images as reference. Materials and Methods: Image quality metrics, including spatial resolution/modular transfer function (MTF), slice sensitivity profile (SSP), noise performance and image uniformity, contrast-noise ratio (CNR) and low-contrast resolution, geometric accuracy, and CT number (HU) accuracy, were evaluated on phantom images. Patient images were evaluated mainly qualitatively. Results: On phantom images the MTF10% is about 0.68 lp/mm for kVCT in PET/CT Linac. The SSP agreed with nominal slice thickness within 0.7 mm. The diameter of the smallest visible target (1% contrast) is about 5 mm using medium dose mode. The image uniformity is within 2.0 HU. The geometric accuracy tests passed within 0.5 mm. Relative to CT simulator images, the noise is generally higher and the CNR is lower in PET/CT Linac kVCT images. The CT number accuracy is comparable between the two systems with maximum deviation from the phantom manufacturer range within 25 HU. On patient images, higher spatial resolution and image noise are observed on PET/CT Linac kVCT images. Conclusions: Major image quality metrics of the PET/CT Linac kVCT were within vendor-recommended tolerances. Better spatial resolution but higher noise and better/comparable low contrast visibility were observed as compared to a CT simulator when images were acquired with clinical protocols.

Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline.

PURPOSE: This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent. METHODS: ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology. RESULTS: Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation. CONCLUSIONS: Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances.

American Radium Society Appropriate Use Criteria for Radiation Therapy in the Multidisciplinary Management of Thymic Carcinoma.

Importance: Thymic carcinoma is rare, and its oncologic management is controversial due to a paucity of prospective data. For this reason, multidisciplinary consensus guidelines are crucial to guide oncologic management. Objective: To develop expert multidisciplinary consensus guidelines on the management of common presentations of thymic carcinoma. Evidence Review: Case variants spanning the spectrum of stage I to IV thymic carcinoma were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel to address management controversies. A comprehensive review of the English-language medical literature from 1980 to 2021 was performed to inform consensus guidelines. Variants and procedures were evaluated by the panel using modified Delphi methodology. Agreement/consensus was defined as less than or equal to 3 rating points from median. Consensus recommendations were then approved by the ARS Executive Committee and subject to public comment per established ARS procedures. Findings: The ARS Thoracic AUC panel identified 89 relevant references and obtained consensus for all procedures evaluated for thymic carcinoma. Minimally invasive thymectomy was rated as usually inappropriate (regardless of stage) due to the infiltrative nature of thymic carcinomas. There was consensus that conventionally fractionated radiation (1.8-2 Gy daily) to a dose of 45 to 60 Gy adjuvantly and 60 to 66 Gy in the definitive setting is appropriate and that elective nodal irradiation is inappropriate. For radiation technique, the panel recommended use of intensity-modulated radiation therapy or proton therapy (rather than 3-dimensional conformal radiotherapy) to reduce radiation exposure to the heart and lungs. Conclusions and Relevance: The ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of thymic carcinoma, perhaps the most well referenced on the topic.

Tumor loss-of-function mutations in STK11/LKB1 induce cachexia.

Cancer cachexia (CC), a wasting syndrome of muscle and adipose tissue resulting in weight loss, is observed in 50% of patients with solid tumors. Management of CC is limited by the absence of biomarkers and knowledge of molecules that drive its phenotype. To identify such molecules, we injected 54 human non-small cell lung cancer (NSCLC) lines into immunodeficient mice, 17 of which produced an unambiguous phenotype of cachexia or non-cachexia. Whole-exome sequencing revealed that 8 of 10 cachexia lines, but none of the non-cachexia lines, possessed mutations in serine/threonine kinase 11 (STK11/LKB1), a regulator of nutrient sensor AMPK. Silencing of STK11/LKB1 in human NSCLC and murine colorectal carcinoma lines conferred a cachexia phenotype after cell transplantation into immunodeficient (human NSCLC) and immunocompetent (murine colorectal carcinoma) models. This host wasting was associated with an alteration in the immune cell repertoire of the tumor microenvironments that led to increases in local mRNA expression and serum levels of CC-associated cytokines. Mutational analysis of circulating tumor DNA from patients with NSCLC identified 89% concordance between STK11/LKB1 mutations and weight loss at cancer diagnosis. The current data provide evidence that tumor STK11/LKB1 loss of function is a driver of CC, simultaneously serving as a genetic biomarker for this wasting syndrome.

Race, Ethnicity, and Socioeconomic Factors as Determinants of Cachexia Incidence and Outcomes in a Retrospective Cohort of Patients With Gastrointestinal Tract Cancer.

PURPOSE: Cachexia is a paraneoplastic syndrome of unintentional adipose and muscle tissue wasting with severe impacts to functionality and quality of life. Although health inequities across minority and socioeconomically disadvantaged groups are known, the role of these factors in cachexia progression is poorly characterized. This study aims to evaluate the relationship between these determinants and cachexia incidence and survival in patients with gastrointestinal tract cancer. METHODS: Through retrospective chart review from a prospective tumor registry, we established a cohort of 882 patients with gastroesophageal or colorectal cancer diagnosed between 2006 and 2013. Patient race, ethnicity, private insurance coverage, and baseline characteristics were evaluated through multivariate, Kaplan-Meier, and Cox regression analyses to determine associations with cachexia incidence and survival outcomes. RESULTS: When controlling for potentially confounding covariates (age, sex, alcohol and tobacco history, comorbidity score, tumor site, histology, and stage), Black (odds ratio [OR], 2.447; P < .0001) and Hispanic (OR, 3.039; P < .0001) patients are at an approximately 150% and 200%, respectively, greater risk of presenting with cachexia than non-Hispanic White patients. Absence of private insurance coverage was associated with elevated cachexia risk (OR, 1.439; P = .0427) compared to privately insured patients. Cox regression analyses with previously described covariates and treatment factors found Black race (hazard ratio [HR], 1.304; P = .0354) to predict survival detriments, while cachexia status did not reach significance (P = .6996). CONCLUSION: Our findings suggest that race, ethnicity, and insurance play significant roles in cachexia progression and related outcomes that are not accounted for by conventional predictors of health. Disproportionate financial burdens, chronic stress, and limitations of transportation and health literacy represent targetable factors for mitigating these health inequities.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.

Racial, Ethnic, and Socioeconomic Characteristics Independently Predict for Cachexia Risk and Associated Survival Outcomes in Stage IV NSCLC: A Brief Report.

Introduction: Cancer cachexia, found in more than a third of patients with NSCLC, directly leads to functional and survival detriments. As screening and interventions for cachexia and NSCLC improve, deficits in health care access and quality among patients disadvantaged by racial-ethnic and socioeconomic factors must be addressed. Methods: We retrospectively evaluated 957 patients diagnosed with having stage IV NSCLC between 2014 and 2020 in Dallas, Texas. Cachexia was retrospectively assessed by applying criteria for substantial unintentional weight loss in the time leading up to cancer diagnosis. Nonparametric, parametric, multivariate logistic regression, and Kaplan-Meier analyses were conducted to evaluate for variables potentially associated with cachexia incidence and survival. Results: In multivariate analysis including age, sex, comorbidities, body mass index, risk behaviors, and tumor characteristics, Black race and Hispanic ethnicity were independently associated with more than a 70% increased risk of presenting with cachexia at the time of NSCLC diagnosis (p < 0.05). When private insurance status was included as a covariate, this association was diminished for Hispanic patients only. Black patients presented with stage IV disease at an average of approximately 3 years younger than White patients (Kruskal-Wallis p = 0.0012; t test p = 0.0002). Cachexia status at diagnosis consistently predicted for survival detriments, further highlighting the importance of addressing differential cachexia risk across racial-ethnic groups. Conclusions: Fundamentally, our findings reveal elevated cachexia risk in Black and Hispanic patients with stage IV NSCLC with associated survival detriments. These differences are not fully accounted for by traditional determinants of health and suggest novel avenues for addressing oncologic health inequities.

Addressing the genetic/nongenetic duality in cancer with systems biology.

The dogma that cancer is a genetic disease is being questioned. Recent findings suggest that genetic/nongenetic duality is necessary for cancer progression. A think tank organized by the Shraman Foundation's Institute for Theoretical Biology compiled key challenges and opportunities that theoreticians, experimentalists, and clinicians can explore from a systems biology perspective to provide a better understanding of the disease as well as help discover new treatment options and therapeutic strategies.

T Stage and Pretreatment Standardized Uptake Values Predict Tumor Recurrence With 5-Fraction SABR in Early-Stage Non-Small Cell Lung Cancer.

Purpose: Five-fraction stereotactic ablative radiotherapy (SABR) regimens are frequently used to treat centrally located early-stage non-small cell lung cancer or disease in the proximity of the chest wall as a means of optimizing tumor control and reducing treatment toxicity. However, increasing these SABR regimens to 5 fractions may reduce tumor control outcomes. We sought to identify the clinical parameters predictive of treatment failures with these 5-fraction courses. Methods: Ninety patients with T1-2 non-small cell lung cancer were treated with 50 or 60 Gy in 5 fractions. Failure over time was modeled using cumulative incidences of local, regional, or distant failure, with death as a competing risk. Cox proportional hazards analysis for incidences of failure was performed to control for patient variables. Results: Of 90 patients, 24 of 53 patients with T1 tumors and 19 of 37 patients with T2 tumors received 50 Gy SABR, and the other 47 patients received 60 Gy. Two-year overall survival and progression-free survival for the whole cohort were 75.8% and 59.3%, respectively. Total SABR dose (50 vs 60 Gy) did not influence survival nor failure rates at 2 and 5 years. Within 2 years of treatment, 7.8% of all patients developed local failure. For all patient and tumor characteristics evaluated, only T stage and pretreatment positron emission tomography standardized uptake values served as predictors of local, regional, and distant failure at 2 and 5 years posttreatment on univariate and multivariable analysis. Conclusions: Five-fraction SABR provides excellent in-field control. T2 and high fluorodeoxyglucose uptake tumors have increased failure rates, suggesting the potential need for adjuvant therapies, which are being assessed in randomized phase 3 trials.

A preponderance of gastrointestinal cancer patients transition into cachexia syndrome.

BACKGROUND: Cancer cachexia is frequently documented by self-reported, single time-point weight histories. This approach lacks the granularity needed to fully elucidate the progression of cachexia syndrome. This study aimed to longitudinally assess body weight changes pre- and post-cancer diagnosis in gastrointestinal (GI) cancer patients. METHODS: Body weights and relevant clinical data recorded in the electronic health record 12 months pre- and post-GI cancer (colorectal, gastroesophageal, hepatobiliary and pancreatic) diagnosis were extracted. Weight loss was categorized by the International Consensus Definition for cachexia. RESULTS: A total of 879 patients were included in the final cohort including patients diagnosed with colorectal (n = 317), hepatocellular (n = 185), biliary (n = 72), pancreatic (n = 186) or gastroesophageal (n = 119) cancer. Stage of disease was equally distributed. Patients without cachexia at diagnosis (n = 608) remained weight stable during the 12 months pre-diagnosis (+0.5 ± 0.5% body weight; P = 0.99). Patients with cachexia at diagnosis (n = 271) remained weight stable 6 to 12 months prior to diagnosis (+0.4 ± 0.8%; P > 0.9999) and lost 8.7 ± 0.6% (P < 0.0001) within the 6 months pre-diagnosis. Patients without cachexia at diagnosis lost more weight post-diagnosis (6.3 ± 0.6%) than patients with cachexia at diagnosis (4.7 ± 1.0%; P = 0.01). Pre-diagnosis weight trajectories did not differ between primary malignancies or stage of disease in patients without or with cachexia at diagnosis (all P ≥ 0.05). Post-diagnosis weight trajectories did differ by primary malignancy (P ≤ 0.0002) and stage (P < 0.0001). In both patients without and with cachexia at diagnosis, colorectal patients lost the least amount of weight post-diagnosis and gastroesophageal patients lost the most amount of weight post-diagnosis. Stage 4 patients without or with cachexia at diagnosis lost the most weight post-diagnosis (P ≤ 0.0003). Regardless of cachexia status at diagnosis, patients lost more weight when treated with systemic therapy (7.1 ± 0.7%; P < 0.0001; n = 419) or radiation therapy (8.4 ± 1.4%; P = 0.02; n = 116) compared to those who did not. Patients who did not have surgery lost more weight post-diagnosis (7.6 ± 1.1%; P < 0.0001; n = 355) compared to those who did have surgery. By 12 months post-diagnosis, 83% of the surviving GI cancer patients in this cohort had transitioned into cachexia syndrome. CONCLUSIONS: Significant weight loss in patients with GI cancer cachexia at diagnosis initiates at least 6 months prior to diagnosis, and most patients will transition into cachexia syndrome post-diagnosis, regardless of pre-diagnosis weight change and stage of disease. These findings punctuate the importance of weight surveillance in cancer detection and earlier palliative interventions post-diagnosis in the GI cancer patient population.