Recurrence patterns and impact of brain metastases in synchronous single organ oligometastatic lung cancer following local ablative treatment - A multicenter analysis.

INTRODUCTION: Local ablative therapy (LAT) improves survival in oligometastatic lung cancer (OMD), but there is limited information on recurrence patterns, re-treatments and in particular the role of brain metastases during the course of disease. We therefore conducted a retrospective multicenter analysis to evaluate course of disease, sequence of therapies and predictors for long-term disease-control in the brain and survival endpoints. PATIENTS AND METHODS: Clinical data of patients with synchronous, single organ OMD with ≤4 metastases were collected from 5 certified German lung cancer centers. All patients underwent thorough initial staging including a 18FDG-PET/CT scan, brain imaging and mediastinal staging, if necessary, and received LAT to all sites of disease. RESULTS: In total, 164 patients were included (median age 62 years [range 41-84], non-squamous histology 80%, N0-1 64%, single metastasis 84%), 103 had brain (cohort A), 61 extracranial metastases (cohort B). With a median follow-up of 66 months, 115 patients (70%) experienced recurrent disease with a different distribution of sites: In cohort A vs. B, brain relapses occurred in 56% vs. 18% and new distant metastases in 5% vs. 40%. In total, LAT for every relapse was possible for 25% (29/115) of the patients. Patients with initial and secondary onset brain metastases experienced long-term disease-control in the brain and subsequently favorable survival with the application of repeated LAT (disease in the brain controlled vs. not-controlled, HR 0.21, p < 0.001). Comparable long-term overall survival was observed in patients with no or isolated brain relapses (5-years OS 74% and 92%) in contrast to patients with extracranial relapses (5-years OS 19.6%, p < 0.001). CONCLUSIONS: Repeated LAT for recurrent synchronous single organ OMD results in a long-term favorable outcome. Disease control in the brain appears crucial and likely determines survival.

Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe.

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

Acceptance and Benefits of Two Different Strategies to Timely Integrate Specialist Palliative Care into Routine Cancer Care: A Randomized Pilot Study.

BACKGROUND/AIMS: The aim of this study is to investigate the acceptance and benefits of two different strategies to timely integrate specialist palliative care (SPC) in routine cancer care: commonly recommended early SPC counselling versus an informational brochure plus SPC counselling upon patients' request. METHODS: Patients diagnosed with incurable cancer within the last 6-12 weeks were sequentially randomized. Endpoints were acceptance of the two strategies after 3 months as well as the use of SPC counselling and psychosocial support, presence of advance directives, palliative care outcome (Integrated Palliative care Outcome Scale [IPOS]), and psychosocial distress (Distress Thermometer [DT]) after 3 and 6 months. In a qualitative part, SPC consultations were analyzed using a content analysis. RESULTS: Overall, 43 patients received SPC counselling and 37 a brochure with SPC counselling on demand. In the brochure group, only one patient later registered for SPC counselling from own initiative. SPC timing was appropriate in 70% of patients (75% counselling/61% brochure, n.s.). Sufficiency, helpfulness and relevance of information, provision of security, and help with finding contacts for specific support were perceived adequate in both groups. No significant differences were found regarding potential effects of the interventions on IPOS or DT after 3 and 6 months. The use of psychosocial support was comparable between the groups and 4 patients had new advance directives (3 counselling/1 brochure). Five key themes of SPC consultations were identified: symptoms, rapport, coping, illness understanding, and advance care planning. CONCLUSIONS: Both SPC integration strategies were well accepted. However, patients seem not to benefit from a brochure in terms of initiating SPC counselling timely after a palliative cancer diagnosis.

Efficacy of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in NSCLC Harboring ERBB2 Mutations.

INTRODUCTION: In contrast to other driver mutations, no targeted therapies have yet been approved in ERBB2-mutated NSCLC (HER2mu NSCLC). Nevertheless, several compounds have revealed promising early efficacy data, which need to be evaluated in the context of current standard approaches. Although data on the efficacy of immune checkpoint inhibitors (ICIs) in second or subsequent lines of treatment remain limited and conflicting, there are virtually no data on patient outcome under ICI/platinum-doublet combinations in the first-line setting. METHODS: We retrospectively evaluated outcomes of patients with HER2mu NSCLC treated with ICI alone or in combination with chemotherapy within the German National Network Genomic Medicine Lung Cancer consortium by means of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: ICI either in combination with chemotherapy or as monotherapy was applied as first-line treatment in 27 patients, whereas 34 received single-agent ICI in second or subsequent lines. Patient characteristics were in line with previously published data. In treatment-naive patients receiving ICI in combination with chemotherapy, the ORR, median PFS, and OS rate at 1 year were 52%, 6 months, and 88%, respectively. In second or subsequent lines, ICI monotherapy was associated with an ORR of 16%, a median PFS of 4 months, and a median OS of 10 months. CONCLUSIONS: ICIs are effective as monotherapy and in combination with platinum-doublet chemotherapy. Therefore, ICI-based treatments may be found as the current standard of care and benchmark for targeted therapies in HER2mu NSCLC.

Lorlatinib Induces Durable Disease Stabilization in a Pancreatic Cancer Patient with a ROS1 p.L1950F Mutation: Case Report.

INTRODUCTION: The prognosis of pancreatic cancer has improved only modestly in recent years. This is partly due to the lack of development in precision oncology including immune oncology in this entity. Rearrangements of the proto-oncogene tyrosine protein kinase ROS1 gene represent driver alterations found especially in lung cancer. Tyrosine kinase inhibitors (TKI) with activity against ROS1 including lorlatinib substantially improved the outcome of this patient population. Anecdotal evidence reports treatment of pancreatic cancer harboring ROS1 fusions with ROS1 TKI, but data concerning treatment of patients with ROS1 point mutations are lacking. CASE PRESENTATION: This case describes a pancreatic cancer patient harboring a ROS1 point mutation that occurred without an underlying ROS1 rearrangement and thus not in the resistance situation. The heavily pretreated patient showed a strong decrease of the tumor biomarkers (CA19-9 and CEA) and radiologically a durable stable disease to the targeted treatment with lorlatinib, thereby achieving a progression-free survival of 12 months. CONCLUSION: Our data are the first to show a clinical benefit from targeted treatment with ROS1 TKI in a cancer patient with a thus far undescribed ROS1 point mutation without a concomitant ROS1 rearrangement. Furthermore, they indicate that ROS1 could be an oncogenic driver in pancreatic cancer. This subgroup could be eligible for targeted treatments, which may contribute to the urgently needed improvement in patient outcome.

Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors.

Circulating tumor cells (CTCs) hold great potential to answer key questions of how non-small cell lung cancer (NSCLC) evolves and develops resistance upon anti-PD-1/PD-L1 treatment. Currently, their clinical utility in NSCLC is compromised by a low detection rate with the established, Food and Drug Administration (FDA)-approved, EpCAM-based CellSearch® System. We tested an epitope-independent method (ParsortixTM system) and utilized it to assess PD-L1 expression of CTCs from NSCLC patients. We prospectively collected 127 samples, 97 of which were analyzed with the epitope-independent system in comparison to the CellSearch system. CTCs were determined by immunocytochemistry as intact, nucleated, CD45-, pankeratins (K)+ cells. PD-L1 status of CTCs was evaluated from 89 samples. With the epitope-independent system, ≥1 CTC per blood sample was detected in 59 samples (61%) compared to 31 samples (32%) with the EpCAM-based system. Upon PD-L1 staining, 47% of patients harbored only PD-L1+CTCs, 47% had PD-L1+ and PD-L1-CTCs, and only 7% displayed exclusively PD-L1-CTCs. The percentage of PD-L1+CTCs did not correlate with the percentage of PD-L1+ in biopsies determined by immunohistochemistry (p = 0.179). Upon disease progression, all patients showed an increase in PD-L1+CTCs, while no change or a decrease in PD-L1+CTCs was observed in responding patients (n = 11; p = 0.001). Our data show a considerable heterogeneity in the PD-L1 status of CTCs from NSCLC patients. An increase of PD-L1+CTCs holds potential to predict resistance to PD-1/PD-L1 inhibitors.

Frequency of Circulating Tumor Cells (CTC) in Patients with Brain Metastases: Implications as a Risk Assessment Marker in Oligo-Metastatic Disease.

Forty percent of non-small cell lung cancer (NSCLC) patients develop brain metastases, resulting in a dismal prognosis. However, patients in an oligo-metastatic brain disease setting seem to have better outcomes. Here, we investigate the possibility of using circulating tumor cells (CTCs) as biomarkers to differentiate oligo-metastatic patients for better risk assessment. Using the CellSearch® system, few CTCs were detected among NSCLC patients with brain metastases (n = 52, 12.5% ≥ two and 8.9% ≥ five CTC/7.5 mL blood) and especially oligo-metastatic brain patients (n = 34, 5.9%, and 2.9%). Still, thresholds of both ≥ two and ≥ five CTCs were independent prognostic indicators for shorter overall survival time among all of the NSCLC patients (n = 90, two CTC ≥ HR: 1.629, p = 0.024, 95% CI: 1.137⁻6.465 and five CTC ≥ HR: 2.846, p = 0.0304, CI: 1.104⁻7.339), as well as among patients with brain metastases (two CTC ≥ HR: 4.694, p = 0.004, CI: 1.650⁻13.354, and five CTC ≥ HR: 4.963, p = 0.003, CI: 1.752⁻14.061). Also, oligo-brain NSCLC metastatic patients with CTCs had a very poor prognosis (p = 0.019). Similarly, in other tumor entities, only 9.6% of patients with brain metastases (n = 52) had detectable CTCs. Our data indicate that although patients with brain metastases more seldom harbor CTCs, they are still predictive for overall survival, and CTCs might be a useful biomarker to identify oligo-metastatic NSCLC patients who might benefit from a more intense therapy.