Lisa W. Le

PURPOSE: Use of chemotherapy at the end of life (EOL) is discouraged, but evidence to guide decisions on the use of novel systemic anticancer treatment (SACT) agents is lacking. We examined trends of use among SACT types and association with health services use at the EOL. MATERIALS AND METHODS: We analyzed Canadian Ontario Cancer Registry data for adults diagnosed with solid tumors or hematologic malignancies within 5 years of death who received SACT between March 2015 and March 2021. Receipt of SACT in the last 30 days of life was categorized as chemotherapy alone, chemotherapy and immunotherapy, immunotherapy alone, and targeted therapy alone. Outcomes included high health services use, including multiple (≥2) emergency department (ED) visits, multiple (≥2) hospitalizations, or any (≥1) intensive care unit admission, and hospital deaths. Segmented linear regression estimated monthly trends; multivariable logistic regression estimated adjusted odds ratios (aORs) of outcomes for various SACT types. RESULTS: Among 68,963 patients, 18,337 (26.6%) received SACT at the EOL. From March 2015 to March 2020, use of SACT at the EOL increased (0.072% per month; P < .001), mainly driven by increased use of immunotherapy alone (0.064% per month; P < .001). Adjusted odds of high health services use and hospital death were more than two-fold greater among patients receiving SACT at the EOL (vs. none); individual aORs of high health services use and hospital death were 2.20 and 2.72 for chemotherapy alone, 2.36 and 3.10 for chemotherapy and immunotherapy, 1.92 and 2.27 for immunotherapy alone, and 1.75 and 2.37 for targeted therapy alone, respectively. CONCLUSION: Use of SACT at the EOL increased significantly over time, driven by increased use of immunotherapy. SACT use at the EOL, regardless of its type, was associated with high health services use and hospital death. Guidelines on the use of SACT at the EOL should include novel cancer treatments.

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients’ samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions.

Purpose Although early palliative care is recommended, resource limitations prevent its routine implementation. We report on the preliminary findings of a mixed methods study involving a randomized controlled trial (RCT) of Symptom screening with Targeted Early Palliative care (STEP) and qualitative interviews. Methods Adults with advanced solid tumors and an oncologist-estimated prognosis of 6–36 months were randomized to STEP or symptom screening alone. STEP involved symptom screening at each outpatient oncology visit; moderate to severe scores triggered an email to a palliative care nurse, who offered referral to in-person outpatient palliative care. Patient-reported outcomes of quality of life (FACT-G7; primary outcome), depression (PHQ-9), symptom control (ESAS-r-CS), and satisfaction with care (FAMCARE P-16) were measured at baseline and 2, 4, and 6 months. Semi-structured interviews were conducted with a subset of participants. Results From Aug/2019 to Mar/2020 (trial halted due to COVID-19 pandemic), 69 participants were randomized to STEP (n = 33) or usual care (n = 36). At 6 months, 45% of STEP arm patients and 17% of screening alone participants had received palliative care (p = 0.009). Nonsignificant differences for all outcomes favored STEP: difference in change scores for FACT-G7 = 1.67 (95% CI: −1.43, 4.77); ESAS-r-CS = −5.51 (−14.29, 3.27); FAMCARE P-16 = 4.10 (−0.31, 8.51); PHQ-9 = −2.41 (−5.02, 0.20). Sixteen patients completed qualitative interviews, describing symptom screening as helpful to initiate communication; triggered referral as initially jarring but ultimately beneficial; and referral to palliative care as timely. Conclusion Despite lack of power for this halted trial, preliminary results favored STEP and qualitative results demonstrated acceptability. Findings will inform an RCT of combined in-person and virtual STEP.

3039 Background: Molecular profiling of tumor tissue is the gold standard for treatment decision making in advanced non-small cell lung cancer. Results may be delayed or unavailable due to insufficient tissue samples or prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma molecular testing as part of the initial diagnostic work-up for patients with suspected advanced lung cancer (NCT04863924). Methods: Patients with radiologic evidence of advanced lung cancer referred to the lung rapid diagnostic program underwent plasma circulating tumor DNA (ctDNA) testing using InVisionFirst-Lung, a next-generation sequencing (NGS) assay targeting 37 genes. Standard tissue testing was performed with comprehensive NGS (Oncomine). The primary endpoint was time to treatment in stage IV NSCLC patients compared to an historical pre-COVID-19 cohort (2018-9). Secondary endpoints included actionable targets identified in plasma, % of patients starting targeted therapy based on liquid biopsy and result turnaround time (TAT). Results: Between July 1 to December 31, 2021, 60 patients were enrolled. Median age was 70 years (range 33-91), 52% were female, 57% Caucasian, 48% never smokers. Of these, 73% had NSCLC, 12% small cell, 10% non-lung pathology and 5% declined tissue biopsy. Of 44 NSCLC patients, 5 (11%) had early-stage disease and underwent curative therapy. Most stage IV patients (79%) had systemic treatment. Median time to treatment initiation in the study cohort was 34 days (n = 31, range 10-90) versus 62 days (n = 101, range 13-159) in the historical cohort (p<0.0001). Two thirds (N = 23) of stage IV NSCLC patients had actionable alterations identified, (30% in current/ex-smokers); 18 started targeted therapy including 10 based on plasma results before tissue results were available. Median TAT was 7 days for plasma from blood draw to reporting (range 4-14) and 26 days for tissue molecular testing (range 11-42), p<0.0001. Concordance was high between plasma and tissue testing (70%). Liquid biopsy identified actionable alterations for 3 patients not identified by tissue NGS. In 4 cases, plasma testing failed to identify actionable alterations detected in tissue, due to undetectable plasma ctDNA. Conclusions: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC leads to faster molecular results and shortens time to treatment compared to tissue testing alone. Supplementing the current standard of tissue molecular testing with a plasma-first approach during the diagnostic work up of patients with suspected advanced lung cancer may increase access to precision medicine and improve patient outcomes. Clinical trial information: NCT04863924.

Background: To assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10^‐2 with overall and failure‐free survival of patients with early‐stage non‐small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT).Methods: A retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10^‐2) from our previous data was used to group patients into low and high SGR cohorts. Log‐rank test was used to compare overall (OS) and failure‐free survivals (FFS) of SGR groups.Results: The median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P < 0.05), male gender (P = P = <0.05) were associated with poorer FFS.Conclusions: High SGR was associated with poorer outcome in patients with early‐stage NSCLC treated with SBRT. SGR can be used in conjunction with other well‐known predictive factors to formulate a practical predictive model to identify subgroups of the patient at higher risk of recurrence after SBRT.

Background: Accurate classification of lung cancer subtypes has become critical in tailoring lung cancer treatment. Our study aimed to evaluate changes in diagnostic testing and pathologic subtyping of advanced non-small-cell lung cancer (NSCLC) over time at a major cancer centre. Methods: In a review of patients diagnosed with advanced NSCLC at Princess Margaret Cancer Centre between 2007–2009 and 2013–2015, diagnostic method, sample type and site, pathologic subtype, and use of immunohistochemistry (IHC) staining and molecular testing were abstracted. Results: The review identified 238 patients in 2007–2009 and 283 patients in 2013–2015. Over time, the proportion of patients diagnosed with adenocarcinoma increased to 73.1% from 60.9%, and diagnoses of NSCLC not otherwise specified (NOS) decreased to 6.4% from 18.9%, p < 0.0001. Use of diagnostic bronchoscopy decreased (26.9% vs. 18.4%), and mediastinal sampling procedures, including endobronchial ultrasonography, increased (9.2% vs. 20.5%, p = 0.0001). Use of IHC increased over time to 76.3% from 41.6% (p < 0.0001). Larger surgical or core biopsy samples and those for which IHC was performed were more likely to undergo biomarker testing (both p < 0.01). Conclusions: Customizing treatment based on pathologic subtype and molecular genotype has become key in treating patients with advanced lung cancer. Greater accuracy of pathology diagnosis is being achieved, including through the routine use of IHC.