Defining the Educational Needs for a Community-Based Hematology/Oncology Career: A National Needs Assessment.

PURPOSE: Little is known about the specific needs during training for hematology/oncology providers practicing in community-based settings. We conducted a national survey of hematologists/oncologists employed in community or academic-community hybrid settings to delineate their educational needs. METHODS: An electronic questionnaire was developed and distributed nationally through professional organizations. We primarily assessed whether survey participants received any specific training during fellowship for community-based practice. Participants were also surveyed regarding training experiences that might have affected their preparation. Relative risk (RR) and 95% CI were calculated using modified Poisson regression to identify factors associated with receiving training specifically for community-based settings. RESULTS: Of 125 participants from across 25 states, 63% were male and 58% identified as White. Less than half (41.6%, binomial 95% CI, 32.8 to 50.7) received any training in a community-based setting. Participants identified rotations in community settings (47%), direct mentorship from community-based physicians (40%), and longitudinal clinic in a community setting (36%) as experiences that would have been valuable. Specific curricula of interest included medical operations and administration (63%), health policy (35%), and quality improvement (27%). Respondents in clinical practice for <10 years were more likely to have received any training specifically for a community-based career (RR, 2.13 [95% CI, 1.18 to 3.86]). CONCLUSION: Our study demonstrates substantial unmet needs as they relate to deliberately training fellows destined for community-based careers. Prospective design of clinical training and curricula emphasizing longitudinal exposures to and key aspects of health care delivery in the community setting are paramount to achieving optimal goal-concordant hematology/oncology training during fellowship.

Integration of Genetic Testing and Counseling in Patients With Breast Cancer in a Large, Multisite Community-Based Practice.

PURPOSE: Despite data-driven consensus recommendations, there remains significant nonadherence to genetic screening and testing. More than 300,000 patients are diagnosed with breast cancer annually, with one third of these estimated to be eligible for homologous recombination deficiency (HRD)/BRCA testing following National Comprehensive Cancer Network (NCCN) guidelines. Only 35% of eligible patients are referred for genetic counseling. METHODS: The goal of this project was to apply NCCN guidelines for germline genetic testing to all new patients with breast cancer within a large community oncology practice to improve HRD/BRCA testing. Plan-Do-Study-Act methodology was used, and cycles were built on a proven teaching infrastructure. In cycle 1, providers were educated and directed to use electronic health record (EHR) templates in the setting of an initial diagnosis visit and treatment planning. Discreet data fields were created in the EHR during cycle 2 to streamline and automate the process. Appropriate patients were referred to the genetics team for further evaluation, counseling, and testing. Adherence to the plan was maintained and measured using data analytic reports and chart audits. RESULTS: Of the 1,203 patients with breast cancer eligible for inclusion, 1,200 (99%) were screened according to NCCN guidelines. Of the screened patients, 631 (52.5%) met the referral/testing criteria. In total, 585 (92.7%) of the 631 were referred to a genetic specialist. Seven percent had previous referrals. A total of 449 (71%) patients were acceptable to genetics referral while 136 (21.5%) patients refused. CONCLUSION: The implemented methods of education, NCCN guidelines imbedded within provider notes, and discreet data fields in the EHR have proven to be highly effective in screening appropriate patients and ordering subsequent genetic referrals.

Sustainable Integration of US Food and Drug Administration-Approved Biosimilars: Pharmacy- Versus Physician-Driven Change.

PURPOSE: Biosimilars are clinically equivalent to branded products yet cost significantly less. Interchangeability is a US Food and Drug Administration (FDA) designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician's consent. Currently, no oncologic biosimilar has FDA approval for interchangeability. METHODS: Building on pharmacy auto-substitution processes with therapeutic interchange, Plan-Do-Study-Act methodology was used to automate conversions from reference biological products to Pharmacy and Therapeutics-/Physician-approved biosimilars. After establishing the baseline metrics, cycle 1 focused on full staff education (completed July 2020) with systematic pharmacy-driven biosimilar conversion initiated in September 2020 for rituximab, trastuzumab, and bevacizumab. Physician-initiated conversion of Neulasta biosimilar products was encouraged but not mandated. During cycle 2 (May 1, 2021-November 30, 2021), pharmacy-driven Neulasta biosimilar conversion was mandated. In cycle 3 (December 1, 2021-April 30, 2023), stakeholder education was reinforced and the sustainability of conversions was confirmed. RESULTS: Systematic pharmacy-driven conversion to biosimilar products improved over cycles 1 and 2 from baseline: 1.8% to 90.3% for rituximab, 9.2% to 89.7% for trastuzumab, and 20.5% to 96.1% for bevacizumab. Physician-driven biosimilar conversion for Neulasta was lower at 12.7% through April 2021. Pharmacy-driven Neulasta biosimilar conversion was initiated during cycle 2, resulting in a conversion rate of 39.7%. The conversion rates remained sustainable through April 2023. CONCLUSION: Pharmacy-driven auto-substitution of biosimilar products results in rapid and statistically significant biosimilar adoption. The pharmacy-based substitution approach was found to be far more effective than physician-driven substitution. Rapid conversion from branded products to FDA-approved biosimilar is feasible, measurable, and sustainable and can be scaled. Barriers to Neulasta conversion warrant further investigation.

Durvalumab real-world treatment patterns and outcomes in patients with stage III non-small-cell lung cancer treated in a US community setting.

Background: For eligible patients with unresectable stage III non-small-cell lung cancer, durvalumab consolidation therapy following chemoradiotherapy is the standard of care. Methods: This was a retrospective study of durvalumab-treated patients diagnosed between 1 August 2017 and 29 February 2020. Electronic health record data were assessed descriptively, with Kaplan-Meier methods used for duration of treatment and overall survival (OS). Results: Among 528 patients (median age 70 years, 51.5% male), the median duration of treatment was 7.1 months (95% CI: 6.0-9.0). Estimated 1- and 2-year OS rates were 83.5 and 64.0%, respectively, with median OS not reached. Conclusion: This study confirmed an OS benefit with durvalumab after chemoradiotherapy in a real-world setting, consistent with the results from the PACIFIC phase III clinical trial.

What is this article about? Durvalumab is a treatment approved for patients with a specific type of lung cancer. Clinical trials have shown durvalumab is an effective therapy for these patients. We conducted this study to better understand what happens to patients treated with durvalumab who were not enrolled in clinical trials. What were the results? Patients who were treated with durvalumab in this study tended to survive as long as patients who received it as part of a clinical trial. What do the results of the study mean? Studies like this one may better represent patients who are less likely to take part in clinical trials. Future studies may examine long-term outcomes of durvalumab and factors associated with better outcomes.

Closing the Testing Gap: Standardization of Comprehensive Biomarker Testing for Metastatic Non-Small-Cell Lung Cancer in a Large Community Oncology Practice.

PURPOSE: Non-small-cell lung cancer (NSCLC), the leading cause of cancer death in the United States, accounts for 85% of all lung cancer cases. Biomarker testing is an integral part of the care of patients with NSCLC. Despite broad consensus recommendations that all patients with metastatic NSCLC (mNSCLC) undergo comprehensive biomarker testing (comprehensive genomic profiling and PD-L1), testing rates remain suboptimal. METHODS: The primary goal of this project was to apply National Comprehensive Cancer Network (NCCN) guidelines for comprehensive biomarker testing to all new patients with mNSCLC within a large community practice. Plan-Do-Study-Act methodology was used, with cycle 1 focused on provider education and the creation of a mNSCLC initial consult Note (electronic health record template/McKesson iKnowMed G2) and accompanying order set. Staging, template/order set utilization, and comprehensive biomarker testing rates were recorded while workflow processes were monitored. Cycle 2 centered on improved cancer staging, data analytic reporting, auditing, and reeducation. RESULTS: The comprehensive biomarker testing rates increased from a historic rate of 68% to 92.7% during the 1-year intervention period. The template utilization rate was 71% with complete staging (TNM stage and relevant biomarkers) documented in 40%. CONCLUSION: Implementation and standardization of comprehensive biomarker testing of patients with mNSCLC in a large multisite community-based oncology practice is feasible and results in significant improvement in comprehensive biomarker testing and reporting. Establishing reliable and measurable tracking metrics to ensure that these new processes are used and maintained can assist in scaling these processes. Efforts to scale this best practice are planned across the US Oncology Network.

MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Nonsquamous NSCLC Progressing On or After Checkpoint Inhibitor Therapy or Chemotherapy.

INTRODUCTION: Sitravatinib, a receptor tyrosine kinase inhibitor targeting TYRO3, AXL, MERTK receptors, and vascular epithelial growth factor receptor 2, can shift the tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPIs) may augment antitumor activity. METHODS: The phase 2 MRTX-500 study evaluated sitravatinib (120 mg daily) with nivolumab (every 2 or 4 wk) in patients with advanced nonsquamous NSCLC who progressed on or after previous CPI (CPI-experienced) or chemotherapy (CPI-naive). CPI-experienced patients had a previous clinical benefit (PCB) (complete response, partial response, or stable disease for at least 12 weeks then disease progression) or no PCB (NPCB) from CPI. The primary end point was objective response rate (ORR); secondary objectives included safety and secondary efficacy end points. RESULTS: Overall, 124 CPI-experienced (NPCB, n = 35; PCB, n = 89) and 32 CPI-naive patients were treated. Investigator-assessed ORR was 11.4% in patients with NPCB, 16.9% with PCB, and 25.0% in CPI-naive. The median progression-free survival was 3.7, 5.6, and 7.1 months with NPCB, PCB, and CPI-naive, respectively; the median overall survival was 7.9 and 13.6 months with NPCB and PCB, respectively (not reached in CPI-naive patients; median follow-up 20.4 mo). Overall, (N = 156), any grade treatment-related adverse events (TRAEs) occurred in 93.6%; grade 3/4 in 58.3%. One grade 5 TRAE occurred in a CPI-naive patient. TRAEs led to treatment discontinuation in 14.1% and dose reduction or interruption in 42.9%. Biomarker analyses supported an immunostimulatory mechanism of action. CONCLUSIONS: Sitravatinib with nivolumab had a manageable safety profile. Although ORR was not met, this combination exhibited antitumor activity and encouraged survival in CPI-experienced patients with nonsquamous NSCLC.

Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial.

BACKGROUND: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRASG12C. We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation who had been previously treated with other anticancer drugs. METHODS: We conducted a randomised, open-label phase 3 trial at 148 centres in 22 countries. We recruited patients aged at least 18 years with KRASG12C-mutated advanced NSCLC, who progressed after previous platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Key exclusion criteria included new or progressing untreated brain lesions or symptomatic brain lesions, previously identified oncogenic driver mutation other than KRASG12C for which an approved therapy is available (eg EGFR or ALK), previous treatment with docetaxel (neoadjuvant or adjuvant docetaxel was allowed if the tumour did not progress within 6 months after the therapy was terminated), previous treatment with a direct KRASG12C inhibitor, systemic anticancer therapy within 28 days of study day 1, and therapeutic or palliative radiation therapy within 2 weeks of treatment initiation. We randomly assigned (1:1) patients to oral sotorasib (960 mg once daily) or intravenous docetaxel (75 mg/m2 once every 3 weeks) in an open-label manner using interactive response technology. Randomisation was stratified by number of previous lines of therapy in advanced disease (1 vs 2 vs >2), ethnicity (Asian vs non-Asian), and history of CNS metastases (present or absent). Treatment continued until an independent central confirmation of disease progression, intolerance, initiation of another anticancer therapy, withdrawal of consent, or death, whichever occurred first. The primary endpoint was progression-free survival, which was assessed by a blinded, independent central review in the intention-to-treat population. Safety was assessed in all treated patients. This trial is registered at ClinicalTrials.gov, NCT04303780, and is active but no longer recruiting. FINDINGS: Between June 4, 2020, and April 26, 2021, 345 patients were randomly assigned to receive sotorasib (n=171 [50%]) or docetaxel (n=174 [50%]). 169 (99%) patients in the sotorasib group and 151 (87%) in the docetaxel group received at least one dose. After a median follow-up of 17·7 months (IQR 16·4-20·1), the study met its primary endpoint of a statistically significant increase in the progression-free survival for sotorasib, compared with docetaxel (median progression-free survival 5·6 months [95% CI 4·3-7·8] vs 4·5 months [3·0-5·7]; hazard ratio 0·66 [0·51-0·86]; p=0·0017). Sotorasib was well tolerated, with fewer grade 3 or worse (n=56 [33%] vs n=61 [40%]) and serious treatment-related adverse events compared with docetaxel (n=18 [11%] vs n=34 [23%]). For sotorasib, the most common treatment-related adverse events of grade 3 or worse were diarrhoea (n= 20 [12%]), alanine aminotransferase increase (n=13 [8%]), and aspartate aminotransferase increase (n=9 [5%]). For docetaxel, the most common treatment-related adverse events of grade 3 or worse were neutropenia (n=13 [9%]), fatigue (n=9 [6%]), and febrile neutropenia (n=8 [5%]). INTERPRETATION: Sotorasib significantly increased progression-free survival and had a more favourable safety profile, compared with docetaxel, in patients with advanced NSCLC with the KRASG12C mutation and who had been previously treated with other anticancer drugs. FUNDING: Amgen.

Oncologists' Perspectives on Individualizing Dose Selection for Patients With Metastatic Cancer.

PURPOSE: Treatment goals for patients with metastatic cancer include prolongation and maintenance of quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy; however, data on oncologists' dose selection strategies and beliefs are lacking. METHODS: We conducted an electronic international survey of medical oncologists who treat patients with breast and/or gastrointestinal cancers. Survey questions addressed experiences with, and attitudes toward, dose reduction at initiation (DRI) of a new systemic therapy for patients with metastatic cancer. RESULTS: Among 3,099 eligible oncologists, 367 responded (response rate 12%). Most (52%) reported using DRI at least 10% of the time to minimize toxicities. Gastrointestinal specialists were more likely to report DRI ≥ 10% of the time (72% v 50% of generalists and 51% of breast specialists, P < .005). Of those who dose reduced ≥ 10% of the time, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Overall, 65% agreed it is acceptable to lower starting doses to reduce side effects even if it compromises efficacy; younger clinicians were more likely to agree (P < .005). There was strong support (89%) for future trials to determine optimal effective, rather than maximum tolerated, dose. CONCLUSION: Oncology practice varies with regard to discussion and individualized selection of starting doses in the metastatic setting. This study demonstrates a need for consideration of shared decision making regarding initial dose selection and strong support among oncologists for clinical studies to define optimal dosing and best practices for individualizing care.

Real-World Outcomes Among Crizotinib-Treated Patients with ROS1-Positive Advanced Non-Small-Cell Lung Cancer: A Community Oncology-Based Observational Study.

BACKGROUND: Crizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC). Data to support long-term clinical benefit in a real-world setting are limited. OBJECTIVE: This study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting. PATIENTS AND METHODS: We conducted a retrospective cohort study using iKnowMed electronic health record data to identify adult patients with ROS1-positive advanced NSCLC who initiated crizotinib between 17 January 2013 (time of the addition of crizotinib for ROS1-positive NSCLC to National Comprehensive Cancer Network (NCCN) treatment guidelines) and 1 June 2019 with a potential follow-up period through 1 December 2019. Patient characteristics were assessed descriptively. Kaplan-Meier analyses were used to evaluate time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS). A Cox proportional hazards model was conducted to determine factors associated with OS. RESULTS: The study cohort included 38 ROS1-positive patients treated with crizotinib. The median age was 68 years (interquartile range 60.0-73.0) and 65.8% were female. Over 50% were current/former smokers, and 18.4% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Overall, 21 (55.3%) patients remained on crizotinib, 10 (26.3%) had evidence of subsequent treatment, and 16 (42.1%) died. The median TTD, TTNT, and OS were 25.2 months [95% confidence interval (CI): 5.2-not reached (NR)], 25.0 months (95% CI 5.2-61.0), and 36.2 months (95% CI 15.9-NR), respectively. In a multivariate Cox regression model, ECOG performance status of 2 was associated with a 4.9-fold higher risk of death (hazard ratio = 4.9; 95% CI 1.1-21.4) compared to ECOG performance status of 0 or 1. CONCLUSIONS: This ROS1-positive NSCLC real-world population was older and had a higher proportion of smokers and of patients with poorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.

Changes Over Time in COVID-19 Severity and Mortality in Patients Undergoing Cancer Treatment in the United States: Initial Report From the ASCO Registry.

PURPOSE: People with cancer are at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ASCO's COVID-19 registry promotes systematic data collection across US oncology practices. METHODS: Participating practices enter data on patients with SARS-CoV-2 infection in cancer treatment. In this analysis, we focus on all patients with hematologic or regional or metastatic solid tumor malignancies. Primary outcomes are 30- and 90-day mortality rates and change over time. RESULTS: Thirty-eight practices provided data for 453 patients from April to October 2020. Sixty-two percent had regional or metastatic solid tumors. Median age was 64 years. Forty-three percent were current or previous cigarette users. Patients with B-cell malignancies age 61-70 years had twice mortality risk (hazard ratio = 2.1 [95% CI, 1.3 to 3.3]) and those age > 70 years had 4.5 times mortality risk (95% CI, 1.8 to 11.1) compared with patients age ≤ 60 years. Association between survival and age was not significant in patients with metastatic solid tumors (P = .12). Tobacco users had 30-day mortality estimate of 21% compared with 11% for never users (log-rank P = .005). Patients diagnosed with SARS-CoV-2 before June 2020 had 30-day mortality rate of 20% (95% CI, 14% to 25%) compared with 13% (8% to 18%) for those diagnosed in or after June 2020 (P = .08). The 90-day mortality rate for pre-June patients was 28% (21% to 34%) compared with 21% (13% to 28%; P = .20). CONCLUSION: Older patients with B-cell malignancies were at increased risk for death (unlike older patients with metastatic solid tumors), as were all patients with cancer who smoke tobacco. Diagnosis of SARS-CoV-2 later in 2020 was associated with more favorable 30- and 90-day mortality, likely related to more asymptomatic cases and improved clinical management.

Assessment of HDR brachytherapy-replicating prostate radiotherapy planning for tomotherapy, cyberknife and VMAT.

A dosimetric study was undertaken to assess the ability of Cyberknife (CK), Volumetric Modulated Arc Therapy (VMAT), and TomoTherapy (Tomo) to generate treatment plans that mimic the dosimetry of high dose-rate brachytherapy (HDR BT) for prostate cancer. The project aimed to assess the potential of using stereotactic body radiotherapy (SBRT) for boost treatment of high-risk prostate cancer patients where HDR BT in combination with conformal external beam radiotherapy (EBRT) is the standard of care. The datasets of 6 prostate patients previously treated with HDR BT were collated. VMAT, CK, and TomoTherapy treatment plans were generated for each dataset using the target and organ-at-risk structures as defined by the Radiation Oncologist during the HDR BT treatment process. The HDR BT plan isodoses were also converted into planning structures to assist the other modalities to achieve a HDR BT-like dose distribution. CK plans were created using both the iris collimator (IC) and a multileaf collimator (MLC). Comparison of the techniques was made based on dose-volume indices. Each plan was created at centres experienced using the respective treatment planning systems (TPS). Planning target volume (PTV V100%), i.e., the volume of the planning target volume (PTV) receiving 100% of the relative dose, in VMAT and TomoTherapy SBRT plans was higher than HDR BT plans. PTV V150% and V200%, i.e., volume of the PTV receiving 150% and 200% of the relative dose, were approached on all the CK MLC and TomoTherapy SBRT plans. However, it is not presently achievable for "virtual brachytherapy" SBRT to replicate the same high intraprostatic doses as HDR BT while meeting the constraints on the organs-at-risk (OARs). Half of the CK IC plans achieved PTV V150% but this was at the expense of high rectal dose. TomoTherapy and CK MLC plans achieved PTV V150% and V200% but the bladder dose was higher compared to CK IC plans. VMAT exhibited excellent PTV coverage based on V100 and OAR sparing, but without any ability to achieve the high intra-prostatic doses of HDR (V150% and V200%). SBRT techniques can be used to deliver hypofractionated radiotherapy to the PTV V100%. Based on the comparison of "physical" dose distributions, SBRT cannot presently achieve the same high intraprostatic doses as HDR BT while respecting the OAR constraints. SBRT still remains an attractive treatment option for delivering hypofractionated treatments for prostate cancer compared to HDR BT, in particular as it is less invasive and less resource intensive. Long-term outcomes of clinical trials comparing HDR BT and SBRT "prostate boosts" may show whether the high intraprostatic doses are clinically significant and correlate with outcomes.

Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics.

MET dysregulation promoting tumorigenesis in non-small cell lung cancer (NSCLC) is associated with worse outcomes following chemotherapy as compared to non-driver mutated NSCLC and occurs either through mutations causing MET exon 14 skipping (METex14) or gene amplification and overexpression that result in enhanced receptor signaling. Capmatinib is the first FDA-approved targeted therapy for NSCLC with METex14 skipping mutations, approved in 2020. FoundationOne® CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diagnostic for capmatinib use. The GEOMETRY mono-1 phase II trial of capmatinib monotherapy demonstrated an overall response rate (ORR) of 68% in treatment naïve (n=28) and 41% in pre-treated (n=69) METex14 skipping advanced NSCLC; in MET amplified advanced NSCLC (gene copy number ≥ 10) ORRs of 40% in treatment naïve and 29% in pre-treated disease was seen. This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne® CDx approval as a companion diagnostic. We detail the practical clinical administration of capmatinib, including dosing and toxicity management, compare capmatinib to other approved and investigational MET-targeted therapies, discuss limitations of capmatinib, and highlight ongoing trials of capmatinib in combinatorial approaches.

Report of the ACPSEM radiation oncology medical physics workforce modelling project task group.

The ACPSEM radiation oncology medical physics workforce modelling project task group was formed to acquire a snapshot of practices in Australia and New Zealand and to develop an activity-based workforce model. To achieve this, two surveys were carried out, capturing the work practices of 98 radiation oncology departments and 182 college members. The member survey provided a snapshot of the current workforce: their demographics, work conditions, professional recognition, and future plans. The facility survey provided an Australian and New Zealand contextualisation of the volume-based activities defined in the International Atomic Energy Agency activity-based radiation oncology staffing model at a granular level. An ACPSEM ROMP workforce model was developed to be a modelling tool applicable at both the facility and sector levels.

Deriving optimal planning organ at risk volume margins in prostate external beam radiotherapy.

Planning organ-at-risk volume (PRV) margins can be applied to the bladder and rectum in prostate external beam radiation therapy (EBRT), in order to incorporate the uncertainties resulting from their inter-fraction motion. For each of a total of 16 patients, the bladder and rectum were delineated on CBCT images for five treatment fractions in addition to the planning CT image set. The bladder and rectum boundary displacements across the images were measured and the frequency and size of organ boundary displacements were evaluated. Subsequently, PRV margins were created to cover a specific percentage of organ boundary motion for a specified percentage of the population. In this investigation, two bladder PRV margins were generated to deal with two bladder conditions of low and high-volume variation among fractions. A combined PRV margin was also generated for the rectum by separating the rectum into three parts and deriving independent PRV margins for each segment. Outward coverage and effectiveness metrics allowed evaluation of the margins.

Investigation of the effects of spinal surgical implants on radiotherapy dosimetry: A study of 3D printed phantoms.

PURPOSE: The use of three-dimensional (3D) printing to develop custom phantoms for dosimetric studies in radiotherapy is increasing. The process allows production of phantoms designed to evaluated specific geometries, patients, or patient groups with a defining feature. The ability to print bone-equivalent phantoms has, however, proved challenging. The purpose of this work was to 3D print a series of three similar spine phantoms containing no surgical implants, implants made of titanium, and implants made of carbon fiber, for future dosimetric and imaging studies. Phantoms were evaluated for (a) tissue and bone equivalence, (b) geometric accuracy compared to design, and (c) similarity to one another. METHODS: Sample blocks of PLA, HIPS, and StoneFil PLA-concrete with different infill densities were printed to evaluate tissue and bone equivalence. The samples were used to develop CT to physical (PD) and effective relative electron density (REDeff ) conversion curves and define the settings for printing the phantoms. CT scans of the printed phantoms were obtained to assess the geometry and densities achieved. Mean distance to agreement (MDA) and DICE coefficient (DSC) values were calculated between contours defining the different materials, obtained from design and like phantom modules. HU values were used to determine PD and REDeff and subsequently evaluate tissue and bone equivalence. RESULTS: Sample objects showed linear relationships between HU and both PD and REDeff for both PLA and StoneFil. The PD and REDeff of the objects calculated using clinical CT conversion curves were not accurate and custom conversion curves were required. PLA printed with 90% infill density was found to have a PD of 1.11 ± 0.03 g.cm-3 and REDeff of 1.04 ± 0.02 and selected for tissue- equivalent phantom elements. StoneFil printed with 100% infill density showed a PD of 1.35 ± 0.03 g.cm-3 and REDeff of 1.24 ± 0.04 and was selected for bone-equivalent elements. Upon evaluation of the final phantoms, the PLA elements displayed PD in the range of 1.10 ± 0.03 g.cm-3 -1.13 ± 0.03 g.cm-3 and REDeff in the range of 1.02 ± 0.03-1.06 ± 0.03. The StoneFil elements showed PD in the range of 1.43 ± 0.04 g.cm-3 -1.46 ± 0.04 g.cm-3 and REDeff in the range of 1.31 ± 0.04-1.33 ± 0.04. The PLA phantom elements were shown to have MDA of ≤1.00 mm and DSC of ≥0.95 compared to design, and ≤0.48 mm and ≥0.91 compared like modules. The StoneFil elements displayed MDA values of ≤0.44 mm and DSC of ≥0.98 compared to design and ≤0.43 mm and ≥0.92 compared like modules. CONCLUSIONS: Phantoms which were radiologically equivalent to tissue and bone were produced with a high level of similarity to design and even higher level of similarity of one another. When used in conjunction with the derived CT to PD or REDeff conversion curves they are suitable for evaluating the effects of spinal surgical implants of varying material of construction.

Real-world progression-free survival in first-line advanced non-small cell lung cancer treated with immunotherapy-based regimens using a US dataset.

While results from clinical trials are important in determining the efficacy of treatment, restrictive eligibility criteria may limit generalizability to patient populations in the real-world setting. Real-world analyses can therefore identify subgroups of patients who may respond differently to specific therapeutic regimens. This supplementary data is supportive to the research article entitled "Real-world outcomes of immunotherapy-based regimens in first-line advanced non-small cell lung cancer" [1]. Using electronic health records data from a large demographically and geographically diverse oncology database, we present real-world progression-free survival (rwPFS) outcomes for patients with advanced non-small cell lung cancer in the United States treated with either first-line immunotherapy as monotherapy or single-agent immunotherapy combined with chemotherapy. rwPFS was estimated for patients in each treatment group using Kaplan-Meier methods; analyses were conducted separately for patients with squamous and non-squamous histology and stratified by Eastern Cooperative Oncology Group performance status, tumor programmed death ligand-1 expression, and presence of brain metastases.

Understanding Contemporary Molecular Biomarker Testing Rates and Trends for Metastatic NSCLC Among Community Oncologists.

INTRODUCTION: Although guidelines recommend testing for actionable biomarkers for patients with advanced or metastatic non-small cell lung cancer (NSCLC), testing rates have varied. This study aimed to assess molecular testing patterns in a large network of US community-based oncology practices. METHODS: This retrospective observational study examined adult patients with newly diagnosed stage IV NSCLC with ≥ 2 visits in The US Oncology Network from July 1, 2016 to September 30, 2019. Testing patterns were examined using electronic health record structured fields and chart review. Structured data were analyzed for the overall study population (cohort A), and structured and unstructured data were analyzed for a select cohort of 300 patients (cohort B). RESULTS: In cohort A (n = 3337), programmed death ligand 1 (37%) was the most frequently tested biomarker documented in structured data, followed by epidermal growth factor receptor (36%), anaplastic lymphoma kinase (35%), ROS1 (20%), and BRAF (16%). According to unstructured data in cohort B (n = 300), epidermal growth factor receptor (80%) was the most frequently tested biomarker, followed by anaplastic lymphoma kinase (79%), programmed death ligand 1 (72%), ROS1 (71%), and BRAF (56%). The proportion of tests ordered prior to first-line (1L) treatment increased from 2016 to 2018 for all biomarkers, as did the proportion of test results available prior to 1L treatment. However, some of the test results became available after 1L or later lines of treatment were in progress. CONCLUSION: Our study found increased testing rates over time and decreases in testing turnaround times. However, rates of testing for all biomarkers still need to improve, as does completion of testing prior to initiation of therapy.

Real-world outcomes of immunotherapy-based regimens in first-line advanced non-small cell lung cancer.

BACKGROUND: First-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States. METHODS: Patients aged ≥18 years with confirmed advanced (stage III-IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020. RESULTS: Among 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3-11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3-12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8-12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4-15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort. CONCLUSION: Survival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O-based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens.