Association of patient socioeconomic status with outcomes after palliative treatment for disseminated cancer.

BACKGROUND: Palliative treatment has been associated with improved quality of life and survival for a wide variety of metastatic cancers. However, it is unclear whether the benefits of palliative treatment are uniformly experienced across the US cancer population. We evaluated patterns and outcomes of palliative treatment based on socioeconomic, sociodemographic and treating facility characteristics. METHODS: Patients diagnosed between 2008 and 2019 with Stage IV primary cancer of nine organ sites were analyzed in the National Cancer Database. The association between identified variables, and outcomes concerning the administration of palliative treatment were analyzed with multivariable logistic regression and Cox proportional hazard models. RESULTS: Overall 238,995 (23.6%) of Stage IV patients received palliative treatment, which increased over time for all cancers (from 20.7% in 2008 to 25.6% in 2019). Palliative treatment utilization differed significantly by region (West less than Northeast, OR: 0.55 [0.54-0.56], p < 0.001) and insurance payer status (uninsured greater than private insurance, OR: 1.35 [1.32-1.39], p < 0.001). Black race and Hispanic ethnicity were also associated with lower rates of palliative treatment compared to White and non-Hispanics respectively (OR for Blacks: 0.91 [0.90-0.93], p < 0.001 and OR for Hispanics: 0.79 [0.77-0.81] p < 0.001). CONCLUSIONS: There are important differences in the utilization of palliative treatment across different populations in the United States. A better understanding of variability in palliative treatment use and outcomes may identify opportunities to improve informed decision making and optimize quality of care at the end-of-life.

The National Cancer Database Conforms to the Standardized Framework for Registry and Data Quality.

BACKGROUND: Standardization of procedures for data abstraction by cancer registries is fundamental for cancer surveillance, clinical and policy decision-making, hospital benchmarking, and research efforts. The objective of the current study was to evaluate adherence to the four components (completeness, comparability, timeliness, and validity) defined by Bray and Parkin that determine registries' ability to carry out these activities to the hospital-based National Cancer Database (NCDB). METHODS: Tbis study used data from U.S. Cancer Statistics, the official federal cancer statistics and joint effort between the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI), which includes data from National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) to evaluate NCDB completeness between 2016 and 2020. The study evaluated comparability of case identification and coding procedures. It used Commission on Cancer (CoC) standards from 2022 to assess timeliness and validity. RESULTS: Completeness was demonstrated with a total of 6,828,507 cases identified within the NCDB, representing 73.7% of all cancer cases nationwide. Comparability was followed using standardized and international guidelines on coding and classification procedures. For timeliness, hospital compliance with timely data submission was 92.7%. Validity criteria for re-abstracting, recording, and reliability procedures across hospitals demonstrated 94.2% compliance. Additionally, data validity was shown by a 99.1% compliance with histologic verification standards, a 93.6% assessment of pathologic synoptic reporting, and a 99.1% internal consistency of staff credentials. CONCLUSION: The NCDB is characterized by a high level of case completeness and comparability with uniform standards for data collection, and by hospitals with high compliance, timely data submission, and high rates of compliance with validity standards for registry and data quality evaluation.

Identifying Opportunities to Deliver High-Quality Cancer Care Across a Health System: A Clinical Responsibility.

OBJECTIVE: We examined process-related quality metrics for oral squamous cell carcinoma (OSCC) depending on treating facility type across a health system and region. STUDY DESIGN: Retrospective in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidelines. SETTING: Single health system and region. METHODS: Patients with OSCC diagnosed between 2012 and 2018 were identified from tumor registries of 6 hospitals (1 academic and 5 community) within a single health system. Patients were categorized into 3 care groups: (1) solely at the academic center, (2) solely at community facilities, and (3) combined care at academic and community facilities. Primary outcome measures were process-related quality metrics: positive surgical margin rate, lymph node yield (LNY), adjuvant treatment initiation ≤6 weeks, National Comprehensive Cancer Network (NCCN)-guideline adherence. RESULTS: A total of 499 patients were included: 307 (61.5%) patients in the academic-only group, 101 (20.2%) in the community-only group, and 91 (18.2%) in the combined group. Surgery at community hospitals was associated with increased odds of positive surgical margins (11.9% vs 2.5%, odds ratio [OR]: 47.73, 95% confidence interval [CI]: 11.2-275.86, P < .001) and lower odds of LNY ≥ 18 (52.8% vs 85.9%, OR: 0.15, 95% CI: 0.07-0.33, P < .001) relative to the academic center. Compared with the academic-only group, odds of adjuvant treatment initiation ≤6 weeks were lower for the combined group (OR: 0.30, 95% CI: 0.13-0.64, P = .002) and odds of NCCN guideline-adherent treatment were lower in the community only group (OR: 0.35, 95% CI: 0.18-0.70, P = .003). CONCLUSION: Quality of oral cancer care across the health system and region is comparable to or better-than national standards, indicating good baseline quality of care. Differences by facility type and fragmentation of care present an opportunity for bringing best in-class cancer care across an entire region.

Survival Among Patients With High-Risk Gastrointestinal Cancers During the COVID-19 Pandemic.

Importance: Prior reports demonstrated that patients with cancer experienced worse outcomes from pandemic-related stressors and COVID-19 infection. Patients with certain malignant neoplasms, such as high-risk gastrointestinal (HRGI) cancers, may have been particularly affected. Objective: To evaluate disruptions in care and outcomes among patients with HRGI cancers during the COVID-19 pandemic, assessing for signs of long-term changes in populations and survival. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database to identify patients with HRGI cancer (esophageal, gastric, primary liver, or pancreatic) diagnosed between January 1, 2018, and December 31, 2020. Data were analyzed between August 23 and September 4, 2023. Main Outcome and Measures: Trends in monthly new cases and proportions by stage in 2020 were compared with the prior 2 years. Kaplan-Meier curves and Cox regression were used to assess 1-year mortality in 2020 compared with 2018 to 2019. Proportional monthly trends and multivariable logistic regression were used to evaluate 30-day and 90-day mortality in 2020 compared with prior years. Results: Of the 156 937 patients included in this study, 54 994 (35.0%) were aged 60 to 69 years and 100 050 (63.8%) were men. There was a substantial decrease in newly diagnosed HRGI cancers in March to May 2020, which returned to prepandemic levels by July 2020. For stage, there was a proportional decrease in the diagnosis of stage I (-3.9%) and stage II (-2.3%) disease, with an increase in stage IV disease (7.1%) during the early months of the pandemic. Despite a slight decrease in 1-year survival rates in 2020 (50.7% in 2018 and 2019 vs 47.4% in 2020), survival curves remained unchanged between years (all P > .05). After adjusting for confounders, diagnosis in 2020 was not associated with increased 1-year mortality compared with 2018 to 2019 (hazard ratio, 0.99; 95% CI, 0.97-1.01). The rates of 30-day (2.1% in 2018, 2.0% in 2019, and 2.1% in 2020) and 90-day (4.3% in 2018, 4.4% in 2019, and 4.6% in 2020) operative mortality also remained similar. Conclusions and Relevance: In this retrospective cohort study, a period of underdiagnosis and increase in stage IV disease was observed for HRGI cancers during the pandemic; however, there was no change in 1-year survival or operative mortality. These results demonstrate the risks associated with gaps in care and the tremendous efforts of the cancer community to ensure quality care delivery during the pandemic. Future research should investigate long-term survival changes among all cancer types as additional follow-up data are accrued.

So Now We Know-Reflections on the Extent of Resection for Stage I Lung Cancer.

Lobectomy has been the standard treatment for stage I lung cancer in healthy patients, largely based on a randomized trial published in 1995. Nevertheless, research has continued regarding the role of sublobar resection. Three additional randomized trials addressing resection extent in healthy patients have recently been published. These 4 trials involve differences in design, eligibility, interventions, and intraoperative processes. Patients were ineligible if intraoperative assessment demonstrated stage > IA or inadequate resection margins. All trials consistently show no differences in perioperative morbidity, mortality, and postoperative changes in lung function between sublobar resection and lobectomy-consistent with other nonrandomized evidence. Long-term outcomes are generally encouraging of lesser resection, but some inconsistencies are apparent. The 2 larger recent trials demonstrated no overall survival difference while the others suggested better survival after lobectomy versus sublobar resection. Recurrence-free survival was found to be the same after lobectomy versus sublobar resection in 3 trials, despite higher locoregional recurrences after sublobar resection. The low 5-year recurrence-free survival (64%, regardless of resection extent) in 1 recent trial highlights the need for further optimization. Thus, there is high-level evidence that sublobar resection is a reasonable alternative to lobectomy in healthy patients. However, variability in long-term results suggests that aspects of patients, tumors and interventions need to be better understood. Therefore, we propose to apply sublobar resection cautiously; especially because there are no short-term benefits. Sublobar resection requires careful attention to intraoperative details (nodes, margins), and may be best suited for less aggressive (eg, ground glass, slow growing) tumors.

Medicaid Expansion Under the Affordable Care Act and Early Mortality Following Lung Cancer Surgery.

Importance: Medicaid expansion under the Patient Protection and Affordable Care Act is associated with gains in health insurance coverage, earlier stage diagnosis, and improved survival among patients with cancer. Objective: To examine the association of Medicaid expansion with changes in early mortality among adults undergoing surgical resection of non-small cell lung cancer (NSCLC), a setting in which access to care is a major determinant of survival. Design, Setting, and Participants: This cohort study used the National Cancer Database to identify 14 984 adults 45 to 64 years of age who underwent surgical resection of NSCLC between 2008 and 2019. Analysis was conducted between March 28, 2021, and September 1, 2023. Exposure: State of residence Medicaid expansion status. Main Outcomes and Measures: Descriptive statistics were used to compare study population characteristics by Medicaid expansion status of patients' state of residence. Difference-in-differences analyses were used to evaluate the association between Medicaid expansion and postoperative mortality before implementation of the ACA (2008-2013) vs after (2014-2019). Results: Among 14 984 adults included, the mean (SD) age was 56.3 (5.1) years, 54.6% were women, and 62.1% lived in Medicaid expansion states. Both 30-day (from 0.97% to 0.26%) and 90-day (from 2.63% to 1.32%) postoperative mortality decreased from before the ACA to after among patients residing in Medicaid expansion states (both P < .001) but not in nonexpansion states (30-day mortality before the ACA, 0.75% vs after the ACA, 0.68%; P = .74; and 90-day mortality before the ACA, 2.43% vs after the ACA, 2.20%; P = .57), leading to a difference-in-differences of -0.64 percentage points (95% CI, -1.19 to -0.08; P = .03) for 30-day mortality and -1.08 percentage points (95% CI, -2.08 to -0.08; P = .03) for 90-day mortality. The difference-in-differences for in-hospital mortality was not significant (P = .34) between expansion states (1.41% before the ACA to 0.77% after the ACA; 0.63 percentage point decrease; P = .004) and nonexpansion states (1.49% before the ACA to 1.20% after the ACA; 0.30 percentage point decrease; P = .29). Conclusions and Relevance: In this cohort study of patients with NSCLC, Medicaid expansion was associated with declines in 30- and 90-day postoperative mortality following hospital discharge. These findings suggest that Medicaid expansion may be an effective strategy for improving access to care and cancer outcomes in this population.

Overall survival in low-comorbidity patients with stage I non-small cell lung cancer who chose stereotactic body radiotherapy compared to surgery.

OBJECTIVE: To evaluate trends in the utilization of stereotactic body radiotherapy (SBRT) and to compare overall survival (OS) of patients with early-stage non-small cell lung cancer (NSCLC) undergoing SBRT versus those undergoing surgery. METHODS: The National Cancer Database was queried for patients without documented comorbidities who underwent surgical resection (lobectomy, segmentectomy, or wedge resection) or SBRT for clinical stage I NSCLC between 2012 and 2018. Peritreatment mortality and 5-year OS were compared among propensity score-matched cohorts. RESULTS: A total of 30,658 patients were identified, including 24,729 (80.7%) who underwent surgery and 5929 (19.3%) treated with SBRT. Between 2012 and 2018, the proportion of patients receiving SBRT increased from 15.9% to 26.0% (P < .001). The 30-day mortality and 90-day mortality were higher among patients undergoing surgical resection versus those receiving SBRT (1.7% vs 0.3%, P < .001; 2.8% vs 1.7%, P < .001). In propensity score-matched patients, OS favored SBRT for the first several months, but this was reversed before 1 year and significantly favored surgical management in the long term (5-year OS, 71.0% vs 41.8%; P < .001). The propensity score-matched analysis was repeated to include only SBRT patients who had documented refusal of a recommended surgery, which again demonstrated superior 5-year OS with surgical management (71.4% vs 55.9%; P < .001). CONCLUSIONS: SBRT is being increasingly used to treat early-stage lung cancer in low-comorbidity patients. However, for patients who may be candidates for either treatment, the long-term OS favors surgical management.

Respect the Middle Lobe: Perioperative Risk of Bilobectomy Compared With Lobectomy and Pneumonectomy.

BACKGROUND: In some cases of right-sided lung cancer, tumor extension, bronchial involvement, or pulmonary artery infiltration may necessitate bilobectomy. Although the middle lobe is believed to represent a fraction of total lung function, the morbidity and mortality associated with bilobectomy is not well described. METHODS: We retrospectively identified patients in The Society of Thoracic Surgeons Database who underwent lobectomy, bilobectomy, or pneumonectomy for lung cancer from 2009 to 2017. The primary outcome was 30-day perioperative mortality. We performed propensity matching by patient demographics, comorbidities, and perioperative variables for each surgical type against bilobectomy and ran Cox proportional hazard models. Secondary outcomes of 30-day morbidity and mortality of upper vs lower bilobectomy were also compared. RESULTS: Within the study period 2911 bilobectomy, 65,506 lobectomy, and 3370 pneumonectomy patients met the inclusion criteria. Patients undergoing pneumonectomy and bilobectomy had fewer comorbidities than lobectomy patients. After propensity matching 30-day mortality of bilobectomy was comparable with left pneumonectomy (hazard ratio [HR], 1.35; 95% CI, 0.95-1.91; P = .09) and significantly worse than left (HR, 0.40; 95% CI, 0.29-0.56; P < .0001) or right (HR, 0.43; 95% CI, 0.31-0.59; P < .0001) lobectomy. Bilobectomy was associated with a survival advantage compared with right pneumonectomy (HR, 2.54; 95% CI, 1.72-3.74; P < .0001). Thirty-day morbidity was higher for bilobectomy compared with lobectomy, and upper bilobectomy had a significant unadjusted 30-day mortality advantage compared with lower bilobectomy (98.3% vs 97%, P = .04). CONCLUSIONS: The morbidity and mortality of bilobectomy is significantly worse than lobectomy and is comparable with left pneumonectomy. The addition of middle lobectomy to a pulmonary resection is not without risk and should be carefully considered during preoperative risk stratification.

Impact of the COVID-19 Pandemic on Lung Cancer Screening Processes in a Northeast Tertiary Health Care Network.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic disrupted health care systems, including implementation of lung cancer screening programs. The impact and recovery from this disruption on screening processes is not well appreciated. Herein, the radiology database of a Northeast tertiary health care network was reviewed before and during the pandemic (2013-2022). In the 3 months before the pandemic, an average of 77.3 lung cancer screening with computed tomography scans (LCS-CT) were performed per month. The average dropped to 23.3 between April and June of 2020, whereas COVID-19 hospitalizations peaked at 1604. By July, average hospitalizations dropped to 50, and LCS-CTs rose to >110 per month for the remaining year. LCS-CTs did not decline during COVID-19 surges in December of 2021 and 2022. The LCS-CT performance grew by 4.5% in 2020, 69.6% in 2021, and 27.0% in 2022, exceeding projected growth by 722 examinations. This resiliency indicates a potentially smaller impact of COVID-19 on lung cancer diagnoses than initially feared.

Brief Report: Increasing Prevalence of Ground-Glass Nodules and Semisolid Lung Lesions on Outpatient Chest Computed Tomography Scans.

Introduction: The increased use of cross-sectional imaging frequently identifies a growing number of lung nodules that require follow-up imaging studies and physician consultations. We report here the frequency of finding a ground-glass nodule (GGN) or semisolid lung lesion (SSL) in the past decade within a large academic health system. Methods: A radiology system database review was performed on all outpatient adult chest computed tomography (CT) scans between 2013 and 2022. Radiology reports were searched for the terms "ground-glass nodule," "subsolid," and "semisolid" to identify reports with findings potentially concerning for an adenocarcinoma spectrum lesion. Results: A total of 175,715 chest CT scans were performed between 2013 and 2022, with a steadily increasing number every year from 10,817 in 2013 to 21,916 performed in the year 2022. Identification of GGN or SSL on any outpatient CT increased from 5.9% in 2013 to 9.2% in 2022, representing a total of 2019 GGN or SSL reported on CT scans in 2022. The percentage of CT scans with a GGN or SSL finding increased during the study period in men and women and across all age groups above 50 years old. Conclusions: The total number of CT scans performed and the percentage of chest CT scans with GGN or SSL has more than doubled between 2013 and 2022; currently, 9% of all chest CT scans report a GGN or SSL. Although not all GGN or SSL radiographic findings represent true adenocarcinoma spectrum lesions, they are a growing burden to patients and health systems, and better methods to risk stratify radiographic lesions are needed.

Telehealth Availability for Cancer Care During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: Telehealth was an important strategy for maintaining continuity of cancer care during the coronavirus pandemic and has continued to play a role in outpatient care; however, it is unknown whether services are equally available across cancer hospitals. OBJECTIVE: This study aimed to assess telehealth availability at cancer hospitals for new and established patients with common cancers to contextualize the impact of access barriers to technology on overall access to health care. METHODS: We conducted a national cross-sectional secret shopper study from June to November 2020 to assess telehealth availability at cancer hospitals for new and established patients with colorectal, breast, and skin (melanoma) cancer. We examined facility-level factors to determine predictors of telehealth availability. RESULTS: Of the 312 investigated facilities, 97.1% (n=303) provided telehealth services for at least 1 cancer site. Telehealth was less available to new compared to established patients (n=226, 72% vs n=301, 97.1%). The surveyed cancer hospitals more commonly offered telehealth visits for breast cancer care (n=266, 85%) and provided lower access to telehealth for skin (melanoma) cancer care (n=231, 74%). Most hospitals (n=163, 52%) offered telehealth for all 3 cancer types. Telehealth availability was weakly correlated across cancer types within a given facility for new (r=0.16, 95% CI 0.09-0.23) and established (r=0.14, 95% CI 0.08-0.21) patients. Telehealth was more commonly available for new patients at National Cancer Institute-designated facilities, medical school-affiliated facilities, and major teaching sites, with high total admissions and below-average timeliness of care. Telehealth availability for established patients was highest at Academic Comprehensive Cancer Programs, nongovernment and nonprofit facilities, medical school-affiliated facilities, Accountable Care Organizations, and facilities with a high number of total admissions. CONCLUSIONS: Despite an increase in telehealth services for patients with cancer during the COVID-19 pandemic, we identified differences in access across cancer hospitals, which may relate to measures of clinical volume, affiliation, and infrastructure.

Assessment of a collaborative treatment model for trimodal management of esophageal cancer.

Background: Patients with esophageal cancer often receive care in a collaborative (multi-institutional) treatment model as opposed to a single institutional model. The effect of a collaborative model on the quality of trimodality therapy and survival is unknown. Methods: The National Cancer Database (NCDB) was used to identify patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for esophageal cancer between 2012-2017. Patients who received neoadjuvant therapy and surgery at a single institution were compared to those that received collaborative treatment across multiple institutions. Outcomes included adherence to guideline recommended multiagent chemotherapy, receipt of 41.4-50.4 Gy of radiation, R0 resection, pathologic complete response (pCR), and 5-year survival. Sociodemographics, comorbidities, and tumor characteristics were assessed in bivariate and multivariable analysis. Results: Among 8,396 patients identified, 39% received treatment at a single institution, while 61% received collaborative treatment. Median travel distance to the site of esophagectomy was two times greater for patients receiving collaborative treatment (30 vs. 15 miles; P<0.001). Patients in the collaborative cohort were less likely to receive guideline-recommended multiagent chemotherapy (85% vs. 96%; P<0.001) and 41.4-50.4 Gy of radiation (89% vs. 91%; P=0.01). R0 resection rates were similar (94.4% vs. 93.7%; P=0.17). Patients who received collaborative treatment had an increased rate of pCR (24% vs. 22%; P=0.02). Overall, 90-day and 5-year survival were 92.9% and 42.6% respectively and did not differ significantly between the two groups. Conclusions: Collaborative trimodality treatment of esophageal cancer is a common and reasonable practice model, which may alleviate patient travel burden with only a modest impact on the quality of CRT, pCR, 90-day survival, and 5-year survival.

Alterations in Cancer Treatment During the First Year of the COVID-19 Pandemic in the US.

Importance: The COVID-19 pandemic created challenges to the evaluation and treatment of cancer, and abrupt resource diversion toward patients with COVID-19 put cancer treatment on hold for many patients. Previous reports have shown substantial declines in cancer screening and diagnoses in 2020; however, the extent to which the delivery of cancer care was altered remains unclear. Objective: To assess alterations in cancer treatment in the US during the first year of the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database (NCDB) on patients older than 18 years with newly diagnosed cancer from January 1, 2018, to December 31, 2020. Main Outcomes and Measures: The main outcomes were accessibility (time to treatment, travel distance, and multi-institutional care), availability (proportional changes in cancer treatment between years), and utilization (reductions by treatment modality, hospital type) of cancer treatment in 2020 compared with 2018 to 2019. Autoregressive models forecasted expected findings for 2020 based on observations from prior years. Results: Of 1 229 654 patients identified in the NCDB in 2020, 1 074 225 were treated for cancer, representing a 16.8% reduction from what was expected. Patients were predominately female (53.8%), with a median age of 66 years (IQR, 57-74 years), similar to demographics in 2018 and 2019. Median time between diagnosis and treatment was 26 days (IQR, 0-36 days) in 2020, and median travel distance for care was 11.1 miles (IQR, 5.0-25.3 miles), similar to 2018 and 2019. In 2020, fewer patients traveled longer distances (20.2% reduction of patients traveling >35 miles). The proportions of patients treated with chemotherapy (32.0%), radiation (29.5%), and surgery (57.1%) were similar to those in 2018 and 2019. Overall, 146 805 fewer patients than expected underwent surgery, 80 480 fewer received radiation, and 68 014 fewer received chemotherapy. Academic hospitals experienced the greatest reduction in cancer surgery and treatment, with a decrease of approximately 484 patients (-19.0%) per hospital compared with 99 patients (-12.6%) at community hospitals and 110 patients (-12.8%) at integrated networks. Conclusions and Relevance: This study found that among patients diagnosed with cancer in 2020, access and availability of treatment remained intact; however, reductions in treated patients varied across treatment modalities and were greater at academic hospitals than at community hospitals and integrated networks compared with expected values. These results suggest the resilience of cancer service lines and frame the economic losses from reductions in cancer treatment during the pandemic.

The Representation of Surgery in Oncology Clinical Trials: 2001 to 2022.

BACKGROUND: Surgery is a mainstay of cancer care. Since the advancement of cancer treatment occurs through clinical trials, it is critical to investigate the degree and nature of representation of surgery in oncological clinical trials. METHODS: This observational analysis used publicly available data from clinicaltrials.gov to investigate non-industry-funded oncological clinical trials in the United States between 2012 and 2022. RESULTS: From 2012 to 2022, 1,861 (15.7%) of the 11,843 registered oncologic clinical trials were surgical. There was a 43.2% increase in proportional surgical trials and an 18.9% increase in oncology trials over the last two decades. Surgery+diagnostic-technique trials increased from 5.14 to 12.6% (P < 0.001, 95%CI [- 0.097, - 0.052]), surgery+radiation trials increased from 5.24 to 8.1% (P = 0.004, 95%CI [- 0.047, - 0.0088]), surgery+systemic-therapy trials decreased from 34.5 to 29.2% (P = 0.003, 95%CI [0.018, 0.088]), surgery+supportive-therapy trials increased from 8.0 to 11.3% (P = 0.004, 95%CI [- 0.056, - 0.01]) and 'surgery-as-the-variable' trials decreased from 12.0 to 3.5% (P < 0.001, 95%CI[0.065, 0.1]). Systemic therapy with biologics increased from 38.1 to 53.9% (P < 0.001, 95%CI [- 0.22, - 0.091]). Surgery-vs.-no-surgery trials increased from 16.8 to 37.3% (P = 0.001, 95%CI [- 0.32, - 0.078]). CONCLUSION: Surgical oncology trials increased by 43.2% over the last 10 years. The focus of clinical trials is changing to the encouragement of innovation in more diagnostic and less invasive techniques, and targeted therapies.

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing.