ESMO Clinical Practice Guidelines Research Articles

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

Robotic left apicoposterior bisegmentectomy for non–small cell lung cancer

Robotic left apicoposterior bisegmentectomy for non–small cell lung cancer

Plain language summary and patient perspective of the European Society for Medical Oncology expert consensus statements on treating EGFR-positive non-small-cell lung cancer.

This article provides a plain language summary and patient perspective of a new set of recommendations made by the European Society for Medical Oncology (ESMO for short). These recommendations are also called expert consensus statements. They cover the management of people with a type of lung cancer called epidermal growth factor receptor-positive non-small-cell lung cancer (EGFR-positive NSCLC for short). The ESMO Clinical Practice Guidelines are used by healthcare professionals when treating people with cancer, but they don't necessarily have all the information healthcare professionals need to make decisions for with people with EGFR-positive NSCLC. So, in 2021, 32 healthcare professionals who are experts in treating people with EGFR-positive NSCLC worked together to produce recommendations to fill these gaps about EGFR-positive NSCLC. This was called a consensus-building process and it also included patient advocates. The experts discussed four main topics including how people with different stages of EGFR-positive NSCLC are diagnosed and treated, and how clinical studies are done. They reviewed the scientific information that exists on these subjects. They reached an agreement and developed the recommendations that are summarized here.

Drug Choice for Hyperactive Delirium in Terminally-Ill Cancer Patients: A Nationwide Survey

Delirium is a prevalent neuropsychiatric condition in patients with cancer that increases in patients prior to death. 1 Lawlor PG Gagnon B Mancini IL et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med. 2000; 160: 786-794 Crossref PubMed Scopus (598) Google Scholar Delirium is a distressing symptom for patients with cancer, caregivers, and medical staff. 2 Bush SH Lawlor PG Ryan K et al. Delirium in adult cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018; 29: iv143-iv165 Abstract Full Text Full Text PDF Scopus (66) Google Scholar Therefore, the management of delirium would lead to an improvement in the quality of life of cancer patients and their caregivers.

1586P Improving the management of anaemia in cancer patients receiving chemotherapy: ESMO clinical practice guidelines in action

Anaemia affects up to two-thirds of cancer patients during chemotherapy. It is associated with impaired quality of life and worse overall survival, but is significantly under-treated. 35% of these patients have underlying functional iron deficiency (FID). ESMO guidelines recommend haematinic monitoring and consideration of intravenous iron and erythropoiesis-stimulating agents (ESAs) to reduce red blood cell (RBC) transfusions. Studies have shown that liberal rather than restrictive transfusion policies are associated with negative outcomes in patients with and without cancer. However, evidence from a recent European survey of clinical practice among Oncologists shows that UK practice still relies heavily on RBC transfusions with minimal use of transfusion-sparing agents. A pre-intervention audit was performed of all solid tumour patients who started chemotherapy during September and October 2019 at University Hospital Southampton. Electronic patient records were interrogated to identify how anaemia was treated over the following six months. Results were interpreted against the following audit standard: ESMO Clinical Practice Guidelines - Management of Anaemia and Iron Deficiency. This was followed by a series of interventions including a new anaemia treatment protocol based on the ESMO algorithm, and education sessions for all prescribers. An identical post-intervention audit was then performed of all patients who started chemotherapy during March and April 2021. Table: 1586PPre-interventionPost-interventionTotal patients108106Iron status assessed (%)1.937.5Patients prescribed darbepoetin if Hb≤100g/L (%)330.8Total IV iron doses given112Total RBC units given4427Anaemic patients given ≥1 RBC transfusion (%)26.820.8RBC units per anaemic patient0.790.38 Open table in a new tab Our ‘real world’ data has shown that even with a limited improvement in guideline adherence, using ESAs and correcting FID anaemia can significantly reduce RBC transfusions. For patients this means less time spent in hospital, and less exposure to adverse outcomes of RBC transfusions. This change in practice was also cost-efficient for our centre, with extrapolated annual savings of €24,000 and 180 hours of treatment time for the chemotherapy unit.

P1126: MOSUNETUZUMAB IS EFFICACIOUS AND WELL TOLERATED IN PATIENTS AGED <65 AND ≥65 YEARS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA AND ≥2 PRIOR THERAPIES: SUBGROUP ANALYSIS OF A PIVOTAL PHASE II STUDY

Background: Advancing age is associated with a decline in immune function and an increase in the incidence of comorbidity (Castellino et al. 2017). Vulnerability to treatment-related toxicities may also increase with age. Mosunetuzumab is a T-cell engaging CD20xCD3 bispecific monoclonal antibody (Ab) that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407), mosunetuzumab induced deep and durable remissions and had a favorable safety profile in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior therapies (Budde et al. ASH 2021). Aims: In the current study, we evaluated the efficacy and safety of mosunetuzumab in pts aged <65 and ≥65 years (age stratification per ESMO Clinical Practice Guidelines for management of newly diagnosed and R/R FL; Dreyling et al. 2021) in the pivotal Phase II study. Methods: All pts had Grade (Gr) 1–3a FL and ECOG performance status (PS) 0–1, and were R/R to ≥2 prior therapies, including an anti-CD20 Ab and an alkylating agent. Intravenous mosunetuzumab was given in 21-day cycles with Cycle (C) 1 step-up dosing: C1 Day (D) 1: 1mg; C1D8 2mg; C1D15 and C2D1: 60mg; D1 of C3+: 30mg. Pts with a complete response (CR) by C8 completed therapy; pts with a partial response or stable disease continued treatment for up to 17 cycles, unless disease progression or unacceptable toxicity occurred. The primary endpoint was CR (as best response) rate by PET/CT assessed by Independent Review Committee using standard response criteria (Cheson et al. 2007). Cytokine release syndrome (CRS) was graded using ASTCT criteria (Lee et al. 2019). All pts provided informed consent. Results: As of August 27, 2021, 90 pts had received mosunetuzumab; 67% were aged <65 years and 33% were aged ≥65 years. Of 30 pts aged ≥65 years, median age was 71 years (range: 65–90) and 43% had ECOG PS 1 at entry, 53% had FLIPI 3–5, and 70% had Ann Arbor stage III/IV disease. Median number of prior therapies in the older age group was 3 (range: 2–8); 77% were refractory to a prior anti-CD20 Ab and 43% were double-refractory to a prior anti-CD20 Ab and an alkylating agent. Compared with younger pts, those aged ≥65 years had a numerically higher objective response rate (87% [95% CI: 69–96] vs 77% [95% CI: 64–87]) and CR rate (70% [95% CI: 51–85] vs 55% [95% CI: 42–68]). The 18-month event-free rate for duration of response was 54% (95% CI: 31–76) in pts aged ≥65 years and 59% (95% CI: 43–74) in those aged <65 years. The rate of Gr 3–4 adverse events (AEs) was comparable in the older and younger age groups (73% vs 68%, respectively). A lower rate of serious AEs of any Gr was observed in pts aged ≥65 years (37% vs 52%). One patient in each age group discontinued treatment due to mosunetuzumab-related AEs. CRS occurred less frequently in pts aged ≥65 years than in those aged <65 years (30% vs 52%), while CRS events were predominantly low-Gr in both groups (age ≥65 vs <65 years: Gr 1, 20% vs 28%; Gr 2, 7% vs 22%); high-Gr CRS was uncommon (one patient in each group). All CRS events resolved. No cases of aphasia, seizures, encephalopathy or cerebral edema occurred. Rates of serious AEs of infection (any Gr) were comparable in pts aged ≥65 and <65 years (17% vs 22%, respectively). The PK disposition of mosunetuzumab was also comparable in pts aged ≥65 and <65 years. Summary/Conclusion: Mosunetuzumab is efficacious and well tolerated in older and younger pts with R/R FL and ≥2 prior therapies. In older pts (aged ≥65 years), numerically lower rates of CRS and serious AEs were observed.

P-115 Bevacizumab in metastatic colorectal carcinoma: A retrospective review of real-world efficacy

We present to you a retrospective review of our institutional use of Bevacizumab in colorectal cancer with respect to chemotherapeutic regimen, efficacy and morbidity relating to its use over a 5-year period in the Maltese islands. We also evaluated whether these outcomes were influenced by patient demographics or tumor characteristics including molecular markers e.g., RAS and BRAF where available. Patients with a diagnosis of metastatic colorectal cancer were identified through our cancer registry and chemotherapy prescribing databases. Patient demographics and tumor characteristics (grade, stage, tumor sidedness) including molecular profiling (K-RAS, BRAF V600E, MSI) were collected. Treatment modality including chemotherapeutic combination and previous lines of therapy as well as radiotherapy, surgery or intervention ablation techniques were documented. Morbidity including hospital admissions during bevacizumab therapy including severity of treatment was documented. Our standard of reference for this audit was the ESMO clinical practice guidelines for the management of metastatic colorectal carcinoma (mCRC). The primary endpoint studied was progression free survival (PFS). Individual variables collected were analyzed for their significance using Cox Regression Analysis via SPSS based software. 54 patients were included in our study over a 5-year period (2015-2020). Folfox was preferred as a first line chemotherapy regimen whilst Folfiri was favored as a second line option. Bevacizumab was used in the first line setting in 29% of the patients and 2nd line agent in in 36% of the patients. 14 patients still received bevacizumab despite showing disease progression with mPFS 48.5 weeks while 38 patients discontinued bevacizumab despite progression with an mPFS of 27.5 weeks. 24 patients had a KRAS mutant tumor whilst 18 patients were KRAS wild type. The mPFS for KRAS mutant tumor was 27 weeks when treated with bevacizumab in combination with Folfox (n=8, mPFS=39 weeks) or Folfiri (n=10, mPFS 26 weeks). For those patients with a K-RAS wild type tumor, the mPFS was 35 weeks (Folfox-Bev n=2, mPFS=69 weeks; Folfiri-Bev n=8, mPFS= 43 weeks). The only variables achieving statistical significance were the contribution of age and use of fluoropyrimidine based cytotoxic therapy. The first parameter noted that an age cut off below or equal to 60 years of age in contrast to patients above 60 years of age had variable outcomes. The second criterion related to the use of fluoropyrimidines in combination with bevacizumab in contrast to those patients treated with a non-fluoropyrimidine regimen such as single agent irinotecan or lonsurf. Only 7% of patients experienced severe toxicity needing hospitalization. In our research, we confirm that it is the addition of a fluoropyrimidine-containing regimen to bevacizumab that is statistically significant, especially in the patient cohort under the age of 60 years. This is in line with current data that confirms that bevacizumab in combination with any fluoropyrimidine-based chemotherapy is more effective than any fluoropyrimidine-based chemotherapy alone. We also presume that the younger patient is likely to have better performance status, less co-morbidities and improved tolerability to chemotherapy, possibly explaining the improved outcomes in PFS.

Clinical performance of Immunoscore in stage III colorectal cancer patients in the SCOT and IDEA-HORG cohorts.

196 Background: The ESMO clinical practice guidelines recommend consideration of Immunoscore (IS) for risk assessment of early colon cancer patients. IS clinical performance was assessed in the SCOT and IDEA-HORG trials evaluating 3 vs. 6 months (3m vs. 6m) of mFOLFOX6 adjuvant chemotherapy in stage III colorectal cancer (CRC). Methods: 1,002 formalin-fixed paraffin-embedded (FFPE) tumor samples (762 from SCOT;240 from HORG) were collected, of which 851 were eligible for biomarker analysis. Eligible samples were classified into 2 groups using pre-defined cut-offs (IS-Low, IS- High) and the performance of IS to predict 3 year disease-free survival (3y-DFS) was evaluated. Results: IS was successfully assessed in 846 cases (99%). 615 (72.7%) samples were classified as IS-High (311 and 304 in 3m and 6m arm, respectively). No significant association between IS and patients’ gender, age, PS, BMI or primary tumour location was observed. However, a significant difference between IS-High (43.7%) and IS Low (57.1%) was observed in the proportion of high risk (T4 and/or N2) tumours (p=0.001). Patients with IS-High tumors had significantly longer 3y-DFS (79.4%, 95%CI: 75.9%-82.4%) compared to those with IS-Low tumors (65.0%, 95%CI: 58.3%-70.9%); adjusted hazard ratio (HR) 1.9 (95%CI: 1.46-2.46; p&lt;0.0001). Similarly, IS-High was significantly correlated with longer 3y-DFS in both treatment arms: 78.5% (95% CI 73.4%-82.7%) for IS-High and 65.8% (95% CI 56.1%-73.9%) for IS-Low in 3m arm; 80.3% (95% CI 75.3%-84.5%) for IS-High and 64.4% (95% CI 54.8%-72.6%) for IS-Low in 6m arm. The estimated HRs according to treatment duration and IS classification were 1.80 (95% CI 1.25-2.60) in 3m arm, 2.00 (95% CI 1.38-2.92) in 6m arm and 1.89 (95% CI 1.46-2.47) in the total study population; interaction p = 0.687. Conclusions: The results of this study confirm the prognostic value of IS observed in the IDEA-France trial (Pagès F et al 2020). However, this analysis was not powered to determine the predictive value of IS for treatment duration. Similar analysis of patients treated with CAPOX is warranted.

Clinical Characteristics and Late-Line Treatment Patterns of Patients with Chronic Myeloid Leukemia Who Received 2 Prior Lines of Tyrosine Kinase Inhibitor Therapy in US Community Oncology Practices

BACKGROUND: Current treatment guidelines recommend tyrosine kinase inhibitors (TKIs) as first-line and second-line treatment options for patients with chronic myeloid leukemia (CML). 1,2 However, approximately 20% of CML patients fail to respond to the first- and second-generation TKIs, and evidence-based guidelines for late-line treatment options after failure/intolerance to TKIs are limited. 3,4 Therefore, this study sought to describe the clinical characteristics and real-world treatment patterns of CML patients who received 2 prior lines of TKI therapy.METHODS: A retrospective cohort design was utilized to identify adult CML patients who initiated a new line of therapy (LOT) after 2 prior lines of TKI therapy between 4/2013 and 12/2020 in the Florida Cancer Specialists network's electronic health records (EHR) database. The index LOT date was the start date of a new CML treatment regimen in LOT≥3 after 2 prior lines of TKI therapy. Patients were followed until 1 of the following occurred: death, loss to follow-up (last structured activity in EHR), or end of study period (3/31/2021). Demographic and clinical characteristics were captured during the baseline period starting 3 months prior to the initial CML diagnosis until the index LOT date and included age, gender, race, Eastern Cooperative Oncology Group performance status (ECOG PS) and comorbidity burden. Treatment patterns of all available LOTs from initial CML diagnosis were investigated and the following metrics were captured: regimen details of systemic CML therapies, duration of LOT, treatment-free interval. This study was descriptive in nature and no inferential statistics were computed.RESULTS: A total of 157 patients who initiated a new CML treatment regimen in LOT≥3 after 2 previous lines of TKI therapy were included in this study. The median age of the study sample at initial CML diagnosis was 63.8 years, 57.3% of the sample were male, and 50.3% were White. At index LOT, 46.5% of the sample had an ECOG PS score of 0-1, 5.1% had ECOG PS score of 2-4, and 48.4% had an unknown ECOG PS score. The majority of the sample initiated the index LOT in LOT 3 (n=151; 96.2%) vs in LOT 4 (n=6; 3.8%). The median duration of the index LOT was 6.6 months with median follow-up from index LOT being 23.0 months. After 2 prior lines of TKI therapy, 93.0% of the sample continued on TKIs only, 1.3% initiated a non-TKI CML drug, and 5.7% received a combination of CML drugs. Dasatinib (31.2%) and imatinib (30.6%) were the most commonly used TKIs in the index LOT. There was significant variability in the treatment sequences across LOTs, however, 50.3% of the sample restarted the same TKI in their index LOT which had been used in a prior LOT. A total of 65 patients (41.4%) initiated a new LOT after the index LOT, and the treatment-free interval following the index LOT was 1.8 months, on average.CONCLUSIONS: The majority of the CML patients who received 2 prior lines of TKI therapy continue to cycle through additional LOTs containing TKIs, and half of the patients restart the same TKI used in a prior LOT. The findings of this study highlight the need for better novel therapies that can fill the treatment gap for CML patients who are refractory or intolerant to TKIs. REFERENCES1. Deininger MW, Shah NP, Altman JK, et al. Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(10):1385-1415.2. Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl 4):iv41-iv51.3. Perrotti D, Jamieson C, Goldman J, et al. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120(7):2254-2264.4. Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14(1):44. DisclosuresPatel: Novartis Pharmaceuticals Corporation: Research Funding. Raju: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Coutinho: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Maegawa: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Lunacsek: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Deyoung: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Iorga: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Cao: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company.

Medical therapy of HCC

Medical therapy of HCC

628P Universal germline testing of prostate cancer patients: Are genetic testing guidelines an aid or an impediment to precision therapy?

Pathogenic/Likely pathogenic (P/LP) germline variants occur in 10-15% of all prostate cancer (PCa) patients. However, complex and restrictive testing criteria lead to underutilization of genetic testing. A multi center prospective observational study was conducted to determine the incidence of P/LP variants in PCa patients who met criteria (IC) and did not meet (out of criteria-OOC) personal/family history based genetic testing criteria (e.g. ESMO Clinical Practice Guidelines).

Total thyroidectomy vs. lobectomy in differentiated thyroid cancer: is there a reasonable size cut-off for decision? A narrative review.

To analyze all the most recent guidelines/consensus as well as papers regarding the relationship between size of tumor, type of surgery, and prognosis, and to try to produce a critical synthesis for real practice. Differentiated thyroid cancer (DTC) is characterized by a wide range of biological behavior. The type of intervention can range from lobectomy (LT) to total thyroidectomy (TT), with tumor size being a point of discussion in choosing the treatment. We carried out a search on PubMed, EMBASE, and Cochrane Library, looking at all the guidelines and consensus regarding DTC, as well as examining original articles, inserting as our research keys "total thyroidectomy vs. lobectomy in differentiated thyroid cancer" and "hemithyroidectomy in thyroid cancer". The guidelines and consensus published over the last 5 years were 6 in total: ATA Guidelines, Italian Consensus of Six Italian Societies, United Kingdom National Multidisciplinary Guidelines, ESMO Clinical Practice Guidelines, a Practical Guidance of a Multidisciplinary Panel of Experts, and The Revised Clinical Practise Guidelines on the Management of Thyroid Tumours by the Japanese Association of Endocrine Surgeons. There were 13 papers cited in the guidelines, and we found another 5 original articles, all of which were retrospective studies. The type of initial surgical intervention must of course consider tumor size, but must also take into account all the risk factors, which is paramount in deciding the type of treatment. LT can have some advantages, and can represent an option that can be offered to patients. However, even in the absence of any special risk factors, a review of the literature suggests to us that patients should be informed that LT for tumors of a size between 2 and 4 cm can be associated with an increased risk of LR as well as with a possible reduced OS.

Lack of Systemic Absorption of Topical Mechlorethamine Gel in Patients with Mycosis Fungoides Cutaneous T-Cell Lymphoma

Lack of Systemic Absorption of Topical Mechlorethamine Gel in Patients with Mycosis Fungoides Cutaneous T-Cell Lymphoma

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non–Small Cell Lung Cancer

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Abstract 820: Genomics based personalized oncology of cancer of unknown primary

Abstract Cancers of unknown primary site (CUPs) represent a heterogeneous group of metastatic tumors, which accounts for 3-5% of malignancies. Due to the poor prognosis and limited local and systemic treatment options, there is an urgent need for improvement of molecularly driven treatment strategies. We investigated the molecular profile and clinical course of 70 patients enrolled in a prospective precision oncology registry trial conducted by the National Center for Tumor Diseases (NCT) Heidelberg/Dresden and the German Cancer Consortium (DKTK) that addresses younger adults with advanced-stage cancer across histologies as well as patients with rare tumors (NCT/DKTK MASTER). Molecular analyses included whole genome sequencing (WGS, n=29), whole exome sequencing (WES, n=41) and transcriptome analysis (n=55). All patients were diagnosed with CUP-syndrome, 61/70 (87.1%) of diagnoses fulfilled the ESMO Clinical Practice Guidelines. Progression free survival (PFS) of the first treatment based on MASTER (PFS2) was compared to the PFS of the last prior systemic treatment (PFS1) in each individual patient. Within the coding sequence, we identified 0 to 1386 nonsynonymous point mutations (SNVs, median=41) and 0 to 38 insertions/deletions (indels, median=3) per sample. Hypermutation (≥100 SNVs and indels) was observed in 14 samples. Mutations of TP53 and KRAS were significantly enriched. Analysis of copy-number changes (CNVs) was performed in 51 samples (27 WGS and 24 WES) and revealed complex CNV profiles in most cases. Gains and losses involved single arms or whole chromosomes. Gains in chromosome 8q, 1q and 7 and losses in chromosome 6q and 17p occurred in more than 40% of the patients. Fusions of EML4-ALK and FGFR2 were found in three and six cases, respectively. In one case, pathological reevaluation for NUT midline carcinoma was recommended based on a NUTM1-MXI1 fusion. In total, pathological reevaluation based on characteristic genetic events was recommended in five cases. Germline analysis of 70 cases revealed five pathogenic variants (ACMG Class 5) in CHEK2, BRCA1, CDKN2A, NBN and ERCC3. In addition, one likely pathogenic variant (ACMG Class 4) was found in FH. The molecular tumor board recommended targeted therapy in 56/70 (80.0%) patients which could be applied in 20/56 (35.7%) cases. The molecularly driven treatment approaches translated into a median PFS2/1 ratio of 2.25 (n=17). Median PFS1 was 89 days (range 31-304, n=17) compared to a median PFS2 of 180 days (range 50-805, n=17). For three patients in which PFS1 could not be determined median PFS2 was 305 days (range 182-336). We demonstrate that a comprehensive molecular analysis of CUPs provides clinically relevant information and additional, molecularly stratified treatment approaches in many cases. These targeted therapies can be highly beneficial even in heavily pretreated patients. Citation Format: Maximilian Werner, Lino Möhrmann, Małgorzata Oleś, Andreas Mock, Arne Jahn, Simon Kreutzfeldt, Sebastian Uhrig, Martina Fröhlich, Barbara Hutter, Daniela Richter, Gina Rüter, Ivan Jelas, Rainer Hamacher, Johanna Falkenhorst, Sebastian Wagner, Christian Brandts, Melanie Börries, Anna Illert, Klaus Metzeler, Benedikt Westphalen, Alexander Desuki, Thomas Kindler, Albrecht Stenzinger, Evelin Schröck, Benedikt Brors, Peter Horak, Christoph Heining, Stefan Fröhling, Hanno Glimm. Genomics based personalized oncology of cancer of unknown primary [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 820.

Management of breathlessness in patients with cancer: ESMO Clinical Practice Guidelines

### Highlights Breathlessness, dyspnoea and shortness of breath are synonymous terms to describe the ‘subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity’.1 2 Chronic breathlessness syndrome was recently defined by an international consensus as breathlessness ‘that persists despite optimum treatment for the underlying pathophysiology and causes disability’.3 4 The pathophysiology and characterisation of breathlessness are described in further details in the supplemental material available at ESMO Open online. Breathlessness is often cited as the most distressing symptom experienced by patients with cancer.5 A 2019 systematic review highlighted six major areas of concerns for patients living with breathlessness refractory to disease-modifying treatments, including physical, emotional, spiritual, social, control and context, unifying these under the concept of total breathlessness.6 In addition to the significant functional limitation, breathlessness can have devastating effects on patients’ quality of life (QoL) and is associated with a poor prognosis.7 ### Supplementary data [esmoopen-2020-001038supp001.pdf] This ESMO Clinical Practice Guideline provides an up-to-date, evidence-based approach on the assessment and management of breathlessness in patients with cancer (figure 1). Proper assessment of breathlessness involves screening and in-depth evaluation to characterise the symptom and direct management. Treatments include interventions aimed at reversing any underlying causes, non-pharmacological and pharmacological therapies to palliate breathlessness, and multimodal approaches. Although the focus …

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

P3118CMR Fast-SENC intramyocardial LV &amp; RV segmental strain detects cardiotoxicity during oncology treatment and impact of cardioprotection therapy before echocardiography

Abstract Background The incidence of cardiotoxicity during cancer therapy is underestimated due to limitations of current diagnostic tests. Current biomarkers (BNP, NT-pro-BNP, hs-Troponin, etc.) and imaging calculations (e.g. echocardiography) such as left ventricular ejection fraction (LVEF) are currently included in the guidelines to designate cardiotoxicity during cancer therapy. Unfortunately, these diagnostics identify systemic damage in symptomatic patients after the heart is unable to compensate for regional dysfunction. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular, apical) with 16 LV/6 RV longitudinal segments &amp; three long axis scans (2-, 3-, 4-chamber) with 21 LV/5 RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxane therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. The % of normal fSENC (segmental stain &lt;−17%) with a threshold of 65% showed a sensitivity of 87% and specificity of 89% in detecting cardiotoxicity while echocardiography GLS with a threshold of −17% observed a sensitivity of 20% and specificity of 88%. Figure 1 shows receiver operating characteristic curves for fSENC based on the percent of normal myocardium, and echocardiography global longitudinal strain (GLS) respectively. Global fSENC had substantially lower sensitivity than segmental fSENC despite having higher accuracy than the other global metrics. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical dysfunction due to cardiotoxic response of chemotherapy before other biomarkers and imaging modalities. The ability to detect the subclinical cardiotoxicity of chemotherapy agents, or other pharmacological agents that cause or worsen heart failure, enables proactive prescription of cardioprotective medications to avoid tissue remodeling that precedes systemic cardiac dysfunction and worsening of global measures such as LVEF and current biomarkers.

MS07.05 Stage I (Resectable) NSCLC: Radiation

For patients with a peripheral stage I NSCLC, the non-surgical treatment of choice is stereotactic ablative radiotherapy (SABR). Patients who are fit to undergo surgery, but instead undergo SABR, have a 3-year overall survival ranging from 76-86% [Siva S, Oncologist 2016], which is superior overall survivals in medically unfit patients treated using SABR. In 2013, the ESMO Clinical Practice Guidelines recommeded that surgery ‘should be offered to patients with stage I or II NSCLC who are willing to accept procedure-related risks’ [Vansteenkiste J, Ann Oncol 2013]. In the absence of completed randomized clinical trials of surgery versus SABR, a number of recent propensity score matched analyses have been performed. A pooled meta-analysis of propensity score matched data showed no significant differences in cancer specific survival between the two local treatments [Chen H, IJROBP 2018]. Changes in the treatment patterns for patients with early-stage NSCLC have be reported in a number of countries, all showing an increase in the utilization of SABR in mainly elderly patients [Damhuis R, Ann Oncol 2019; Holmes JA, JNCI Ca Spectrum 2017]. These findings are in part due to the increase in the frail elderly presenting with lung cancer, and to the growing awareness of treatment-related mortality in this population. For example, data from the US National Cancer Database revealed that differences in 30- and 90-day post-treatment mortality between surgery and SABR increased as a function of age, with the largest differences in favor of SABR observed among patients older than 70 years [Stokes WA, JCO 2018[. Ongoing and future randomized studies comparing both modalities will also have to take account of the view of patient preferences. This is illustrated by recent randomized trial of surgery versus SABR (SABRTOOTH, ISRCTN13029788), in which 84 high-risk patients were approached by pulmonologists and oncology nurses for study participation, and 24 (29%) were randomized [Franks K, WCLC 2018]. The main reason for declining study participation was patient preference with 29% preferring surgery and 42% SABR. Overall 9 patients (38%) did not receive their randomized treatment. Of 7 patients who had been randomized to surgery but not undergoing surgery, 6 received SABR, 1 radical radiotherapy. Similarly, of 2 patients randomized to SABR, but who did not undergo SABR, 1 patient received radical radiotherapy, and another was lost to follow-up. Other research which may influence the ongoing debate are the effects of both local therapies on the immune system. The systemic inflammatory response induced after surgery can promote the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response [Krall 2018]. SABR, on the other hand, is actively being investigated as an immunomodulator to enhance systemic anticancer effects [Marciscano AE, IJROBP 2019], with a randomized placebo-controlled trial of immune-checkpoint blockade underway in this population (NCT03833154). REFERENCES Siva S. Curing Operable Stage I Non-Small Cell Lung Cancer With Stereotactic Ablative Body Radiotherapy: The Force Awakens. The Oncologist 2016;21:393–398 Vansteenkiste J. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013 Oct;24 Suppl 6:vi89-98. Chen H. Stereotactic Ablative Radiation Therapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score Studies. Int J Radiat Oncol Biol Phys 101:186-194, 2018 Damhuis R. Annals of Oncology (2019) 30 (suppl_2): ii26-ii30. 10.1093/annonc/mdz064 Holmes JA, JNCI Cancer Spectrum, Volume 1, Issue 1, September 2017, https://doi.org/10.1093/jncics/pkx003 Stokes WA. Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer. J Clin Oncol2018 Mar 1;36(7):642-651. Franks K. SABRTOOTH: A Feasibility Study of SABR Versus Surgery in Patients with Peripheral Stage I NSCLC Considered to be at Higher Risk for Surgery. Proceedings of WCLC 2018 P2.16-16 Marciscano AE. Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities. In press Int J Radiat Oncol Biol Phys 2019 https://doi.org/10.1016/j.ijrobp.2019.02.046 Krall JA. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 10, eaan3464 (2018) surgery, Early-stage lung cancer, stereotactic radiotherapy