QoL during KTd or KRd induction followed by K maintenance or observation in transplant noneligible patients with newly diagnosed multiple myeloma: Longitudinal and cross-sectional analysis of the randomized AGMT 02 study.

Understanding the impact of induction and maintenance therapy on patients' quality of life (QoL) is important for treatment selection. This study aims to compare patient-reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL-C 30 and QOL-MY20 questionnaires in the AGMT-02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health-related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross-sectional comparisons indicated a "slight" superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross-sectional comparisons revealed a "slight" improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with "slight" or "moderate" impairments in several QoL scales compared with the observation group.

Clinical applications of next-generation sequencing-based ctDNA analyses in breast cancer: defining treatment targets and dynamic changes during disease progression.

The advancements in the detection and characterization of circulating tumor DNA (ctDNA) have revolutionized precision medicine and are likely to transform standard clinical practice. The non-invasive nature of this approach allows for molecular profiling of the entire tumor entity, while also enabling real-time monitoring of the effectiveness of cancer therapies as well as the identification of resistance mechanisms to guide targeted therapy. Although the field of ctDNA studies offers a wide range of applications, including in early disease, in this review we mainly focus on the role of ctDNA in the dynamic molecular characterization of unresectable locally advanced and metastatic BC (mBC). Here, we provide clinical practice guidance for the rapidly evolving field of molecular profiling of mBC, outlining the current landscape of liquid biopsy applications and how to choose the right ctDNA assay. Additionally, we underline the importance of exploring the clinical relevance of novel molecular alterations that potentially represent therapeutic targets in mBC, along with mutations where targeted therapy is already approved. Finally, we present a potential roadmap for integrating ctDNA analysis into clinical practice.

Randomized comparison between KTd and KRd induction therapy followed by maintenance therapy with K or observation in transplant-ineligible patients with newly diagnosed multiple myeloma.

Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.

Impact of early cyclosporine A levels on acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation using in vivo T-cell depletion.

BACKGROUND AIMS: Cyclosporin A (CsA) remains a major component of immunosuppressive regimens applied in allogeneic hematopoietic stem cell transplantation (HSCT). The impact of CsA trough levels during the first weeks after HSCT has not yet been investigated specifically in anti-T-lymphocyte globulin (ATLG)-based HSCT from matched related and unrelated donors. METHODS: To address this issue, we have retrospectively examined 307 consecutive matched related (n = 145) and unrelated (n = 162) HSCTs, using peripheral blood stem cells or bone marrow. HSCTs for active, uncontrolled malignancies were excluded. The initial three weeks' average mean CsA trough levels were analyzed in landmark and multi-state models, using a cut-off of 200 ng/mL. RESULTS: CsA levels >200 ng/mL were associated with a reduced risk of acute graft-versus-host disease (GVHD) grade 3-4 at the first-week landmark (subdistribution hazard ratio [SHR] 0.59, P = 0.03) and the second-week landmark (SHR 0.48, P = 0.004), whereas there was no impact at the third-week landmark (HR 0.87, P = 0.69). This was supported by a multi-state model, in which week 1 (hazard ratio [HR] 0.53, P = 0.006) and week 2 (HR 0.48, P = 0.003), but not week 3 (HR 0.80, P = 0.44) CsA levels >200 ng/mL were associated with a reduced acute GVHD 3-4 risk. Relapse incidence was not significantly affected by week 1 through 3 CsA levels. Despite ATLG's inherent GVHD-preventive properties, week 1 CsA trough levels >200 ng/mL following ATLG-based HSCT (n = 220) were associated with a significantly reduced risk of non-relapse mortality (SHR 0.52, P = 0.02) and improved overall survival (HR 0.61, P = 0.02). CONCLUSIONS: Our findings emphasize the continuing importance of ensuring CsA levels ≥200 ng/mL immediately post-transplant in the setting of ATLG-based HSCT.

Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update.

ABSTRACT: Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor-positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.

Survival Outcome in Early-Onset Metastatic Colorectal Cancer: A Multicenter-Matched Pair Analysis.

INTRODUCTION: Survival of patients suffering from metastatic colorectal cancer (mCRC) has increased over the last decades. These benefits appear to be restricted to patients aged 50 and above. However, among the population aged <50, colorectal cancer incidence and mortality rates are significantly rising. The clinical benefit of treatment in this population still is a matter of debate. We aim to compare the clinical outcome between patients aged 50 and younger. METHODS: In this retrospective, observational study, we analyzed data from 1,077 patients treated for mCRC at three cancer centers in Austria from January 2005 to December 2019. Patients were divided into two groups based on age at diagnosis: <50 years (eo-CRC) and >50 years (regular-onset CRC, ro-CRC). Propensity score matching was used to control for potential biases, and survival outcomes were compared between the two groups. RESULTS: The differences in tumor characteristics between eo-CRC and ro-CRC in the overall population were primarily related to tumor sidedness and disease-free survival following intended curative resection. Our data show that eo-CRC patients underwent metastases resection more often and received significantly more lines of treatment in the palliative setting. Overall survival was superior in eo-CRC compared to ro-CRC, even after adjusting for sidedness, timing of metastases, sex, number of treatment lines, and resection of metastases by propensity scoring. CONCLUSION: Our study suggests that younger patients benefit at least to the same magnitude or even more from mCRC-treatment than patients aged 50 or above.

Allogeneic Stem Cell Transplantation in Multiple Myeloma: Risk Factors and Outcomes in the Era of New Therapeutic Options-A Single-Center Experience.

BACKGROUND: Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. METHODS: This retrospective, unicentric analysis included 38 patients with relapsed/refractory multiple myeloma or plasma cell leukemia who underwent allogeneic stem cell transplantation (allo-HSCT) between 2013 and 2022. Survival outcomes, relapse incidence, and non-relapse mortality were calculated according to remission status, date of allo-HSCT, cytogenetic risk status, timing, and number of previous autologous HSCTs. RESULTS: The median PFS was 13.6 months (95% CI, 7.7-30.4) and the median OS was 51.4 months (95% CI, 23.5-NA) in the overall cohort. The cumulative incidence of relapse at 3 years was 57%, and non-relapse mortality was 16%. The median PFS and OS were significantly longer in patients with very good partial remission (VGPR) or better compared to patients with less than VGPR at the time of allo-HSCT (mPFS 29.7 months (95% CI, 13.7-NA) vs. 6.5 months (95% CI, 2.6-17.0); p = 0.009 and mOS not reached vs. 18.6 months (95% CI, 7.0-NA); p = 0.006). CONCLUSION: For selected patients, allo-HSCT may result in favorable overall survival, in part by providing an appropriate hemato-immunological basis for subsequent therapies.

Successful SARS-CoV-2 mRNA Vaccination Program in Allogeneic Hematopoietic Stem Cell Transplant Recipients-A Retrospective Single-Center Analysis.

(1) Background: mRNA COVID-19 vaccines are effective but show varied efficacy in immunocompromised patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients. (2) Methods: A retrospective study on 167 HSCT recipients assessed humoral response to two mRNA vaccine doses, using the manufacturer cut-off of ≥7.1 BAU/mL, and examined factors affecting non-response. (3) Results: Twenty-two percent of HSCT recipients failed humoral response. Non-responders received the first vaccine a median of 10.2 (2.5-88.9) months post-HSCT versus 35.3 (3.0-215.0) months for responders (p < 0.001). Higher CD19 (B cell) counts favored vaccination response (adjusted odds ratio (aOR) 3.3 per 100 B-cells/microliters, p < 0.001), while ongoing mycophenolate mofetil (MMF) immunosuppression hindered it (aOR 0.04, p < 0.001). By multivariable analysis, the time from transplant to first vaccine did not remain a significant risk factor. A total of 92% of non-responders received a third mRNA dose, achieving additional 77% seroconversion. Non-converters mostly received a fourth dose, with an additional 50% success. Overall, a cumulative seroconversion rate of 93% was achieved after up to four doses. (4) Conclusion: mRNA vaccines are promising for HSCT recipients as early as 3 months post-HSCT. A majority seroconverted after four doses. MMF usage and low B cell counts are risk factors for non-response.

Response prediction by mutation- or methylation-specific detection of ctDNA dynamics in pretreated metastatic colorectal cancer.

Background: Serial analysis of circulating tumor DNA (ctDNA) levels is a promising tool for both relapse prediction in the curative setting, as well as predicting clinical benefit from systemic treatment in metastasic colorectal cancer (mCRC). Most data in this context are derived from treatment naive patients. Objective: To predict progressive disease (PD) as early as possible through monitoring of changes in ctDNA levels during systemic treatment in pretreated patients with mCRC. Design: A prospective, single-center, observational study. Methods: Patients treated beyond first-line were prospectively included between February 2020 and September 2021. Blood for ctDNA detection was taken before every treatment cycle from start of treatment until first restaging by CT-scan. ctDNA was detected by mutation- (mut-ctDNA) and methylation-specific ddPCR. Receiver Operating Characteristic (ROC)-analysis was used to describe sensitivity and specificity for prediction of PD at restaging for all time points. Results: A total of 42 patients were included who all carried a mutation in tumor tissue. Detection rate of mut-ctDNA was 88.1% and 74.4% for meth-ctDNA. Absolute ctDNA levels before treatment were prognostic in terms of overall survival. Levels of ctDNA were significantly higher in patients with PD at restaging. Median time from start of treatment to restaging was 93 days (95% CI 88.8-96). After a median of 19 days of treatment (95% CI 16.1-20.2), a decline of either mutation- or methylation-specific ctDNA levels of ⩽58% predicted PD at restaging with a sensitivity/specificity of 92.9/85.7% and 85.7/100%, respectively. Median time to restaging was 66 days (95% CI 56.8-75.2). There was no significant increase of sensitivity/specificity at later time points of ctDNA measurements. Conclusion: Monitoring early changes of ctDNA levels either by mut- or meth-ctDNA allows for early prediction of PD in pretreated patients with mCRC. This has the potential to complement RECIST-based treatment assessment with the aim to switch potentially insufficient treatments as early as possible, which is of particular interest in higher treatment lines.

Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment.

Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics-next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFStargeted/PFSpre-chemotherapy) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7-29.3) vs. 17.5 months (95% CI 1.7-19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.

Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine-A prospective cohort study by the AGMT.

The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.

Impact of the Recipient's Pre-Treatment Blood Lymphocyte Count on Intended and Unintended Effects of Anti-T-Lymphocyte Globulin in Allogeneic Hematopoietic Stem Cell Transplantation.

Background: In allogeneic hematopoietic stem cell transplantation (HSCT), Anti-T-Lymphocyte Globulin (ATLG) may be used for the prevention of severe graft-versus-host disease (GVHD). ATLG targets both the recipient's lymphocytes and those transferred with the graft. Assuming an inverse relation between the recipient's absolute lymphocyte count (ALC) and exposure of remaining ATLG to the graft, we aim to evaluate the impact of the recipient's ALC before the first ATLG administration on the benefits (prevention of GVHD and GVHD-associated mortality) and potential risks (increased relapse incidence) associated with ATLG. Methods: In recipients of HLA-matched, ATLG-based HSCT (n = 311), we assessed the incidence of acute GVHD, GVHD-related mortality and relapse, as well as other transplant-related outcomes, in relation to the respective ALC (divided into tertiles) before ATLG. Results: The top-tertile ALC group had a significantly increased risk of aGVHD (subhazard ratio (sHR) 1.81; [CI 95%; 1.14-2.88]; p = 0.01) and aGVHD-associated mortality (sHR 1.81; [CI 95%; 1.03-3.19]; p = 0.04). At the highest ATLG dose level (≥45 mg/kg), recipients with lowest-tertile ALC had a trend towards increased relapse incidence (sHR 4.19; [CI 95%; 0.99-17.7]; p = 0.05, n = 32). Conclusions: ATLG dosing based on the recipient's ALC may be required for an optimal balance between GVHD suppression and relapse prevention.

Current concepts of anti-EGFR targeting in metastatic colorectal cancer.

Anti-EGFR targeting is one of the key strategies in the treatment of metastatic colorectal cancer (mCRC). For almost two decades oncologists have struggled to implement EGFR antibodies in the mCRC continuum of care. Both sidedness and RAS mutational status rank high among the predictive factors for the clinical efficacy of EGFR inhibitors. A prospective phase III trial has recently confirmed that anti-EGFR targeting confers an overall survival benefit only in left sided RAS-wildtype tumors when given in first line. It is a matter of discussion if more clinical benefit can be reached by considering putative primary resistance mechanisms (e.g., HER2, BRAF, PIK3CA, etc.) at this early stage of treatment. The value of this procedure in daily routine clinical utility has not yet been clearly delineated. Re-exposure to EGFR antibodies becomes increasingly crucial in the disease journey of mCRC. Yet re- induction or re-challenge strategies have been problematic as they relied on mathematical models that described the timely decay of EGFR antibody resistant clones. The advent of liquid biopsy and the implementation of more accurate next-generation sequencing (NGS) based high throughput methods allows for tracing of EGFR resistant clones in real time. These displays the spatiotemporal heterogeneity of metastatic disease compared to the former standard radiographic assessment and re-biopsy. These techniques may move EGFR inhibition in mCRC into the area of precision medicine in order to apply EGFR antibodies with the increase or decrease of EGFR resistant clones. This review critically discusses established concepts of tackling the EGFR pathway in mCRC and provides insight into the growing field of liquid biopsy guided personalized approaches of EGFR inhibition in mCRC.

Prediction of response to systemic treatment by kinetics of circulating tumor DNA in metastatic pancreatic cancer.

Introduction: Pretherapeutic detectable circulating tumor DNA (ctDNA) represents a promising prognostic biomarker for predicting relapse and overall survival in patients with metastatic pancreatic cancer. However, the prognostic value of ctDNA dynamics during treatment has not been studied thus far. We aimed to investigate the correlation between the change of ctDNA levels and response to treatment in patients treated by systemic therapy. Material and methods: CtDNA detection using liquid biopsy (droplet digital PCR (ddPCR) utilizing KRAS G12/13 and, if negative, Q61 commercial test kits) was prospectively performed on patients with stage IV pancreatic cancer i) prior to initiation of systemic chemotherapy and ii) serially every 2 weeks until restaging. Detection rates, levels of ctDNA, and the course of the relative ctDNA change (ctDNA kinetics) were correlated to treatment response and clinical outcome. Results: The detection rate at baseline was 64.3% (45/70), and complete serial measurement records were available for 32 ctDNA-positive patients. Reduction of ctDNA levels below 57.9% of its baseline value at week 2 after treatment initiation was significantly predictive of response to treatment (area under the curve (AUC) = 0.918, sensitivity 91.67%, and specificity 100%) and was associated with prolonged overall survival (OS) (5.7 vs. 11.4 months, p = 0.006) and progression-free survival (PFS) (2.5 vs. 7.7 months, p < 0.000) regardless of treatment line. Pretherapeutic ctDNA detection was independently associated with worse OS in patients receiving a first-line regimen (7 vs. 11.3 months, p = 0.046) and regardless of treatment line (11.4 vs. 15.9 months, p = 0.045) as well as worse PFS (3.4 vs. 10.8 months, p = 0.018). Conclusion: The change in magnitude of ctDNA during systemic treatment allows the prediction of treatment response and is associated with both OS and PFS. This finding adds significant clinical potential to the already established prognostic value of ctDNA positivity in metastatic pancreatic cancer.

Austrian treatment algorithms in HER2-positive metastatic breast cancer: a 2022 update.

In the past 12 months a plethora of relevant novel data for the treatment of metastatic HER2 positive breast cancer were published. To bring this new evidence into a clinical perspective, a group of Austrian breast cancer specialists updated their previously published treatment algorithm for those patients. For this consensus paper a total of eight scenarios were developed in which treatment strategies appropriate for specific patient profiles were evaluated. Consensus was established by detailed discussions of each scenario and by reaching full consensus.

Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents-A Prospective Cohort Study of the AGMT Study-Group.

Background: Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. Aims: To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials. Results: A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3-4 anemia 43.4%, grade 3-4 thrombopenia 36.8%, grade 3-4 neutropenia 36.1%). Grade 3-4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%). Conclusion: The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations.

Data of 'Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage'.

This data article subsumes the data acquiration process, analysis and results of 'Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage' published in European Journal of Surgical Oncology (Eur J Surg Oncol. 2021 Dec 1:S0748-7983(21)00947-1. doi:10.1016/j.ejso.2021.11.138. PMID: 34876329) (Kirchweger et al., 2021). 28.5 mL of blood was obtained from 60 patients with localized pancreatic cancer directly prior to curative intended surgery as well as from 47 patients with metastasized pancreatic cancer (PDAC) directly prior to palliative intended systemic treatment initiation. Cell-free DNA preparation was done on the Chemagic 360 (Perkin Elmer, Waltham, Massachusetts, USA) using the kits CMG-1304 and CMG-844 from the same provider and quantified using the Quantus fluorometer (Promega, Madison, Wisconsin, USA). Screening for most common KRAS alterations (KRAS G12/G13 screening kit and additionally for KRAS Q61 if screening was negative) was performed utilizing the QX200™ Droplet Digital™ PCR System from Bio-Rad (Bio-Rad Laboratories, Hercules, CA, USA). Volumetric analysis was performed on contrast enhanced dual-energy CT scans in the arterial and portal venous phase prior to treatment initiation using Syngo.via (Siemens Healthcare, Forchheim, Germany) on MM Oncology Workflow adhering to RECIST 1.1 criteria (Eisenhauer et al., 2009). CtDNA predicts outcome in localized and disseminated disease. Moreover, it correlates with distant metastasis volume and positive lymph nodes but not primary tumor volume and therefore could indicate subclinical synchronous distant metastases in localized PDAC undetectable by current gold standard (computed tomography).

Updated Austrian treatment algorithm in HER2+ metastatic breast cancer.

A group of Austrian breast cancer specialists met in December 2020 to establish a comprehensive clinical benefit-risk profile of available HER2-targeted therapies based on recent data and to develop an updated treatment algorithm by consensus over several months in 2021. A total of four scenarios were developed in which treatment strategies appropriate for specific patient profiles were evaluated. Consensus was established by detailed discussions of each scenario and by reaching full consensus.

Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage.

INTRODUCTION: Circulating tumor DNA (ctDNA) represents a promising tool for diagnosis, prognosis and treatment monitoring of several malignancies. Its association with tumor burden in pancreatic ductal cancer (PDAC), especially in localized disease, is not fully explored yet. We aimed to investigate the association of pretherapeutic ctDNA levels in localized and metastatic PDAC with tumor volume and clinical outcomes. MATERIAL AND METHODS: Liquid biopsy for ctDNA detection was prospectively obtained from patients with localized or disseminated PDAC prior to either resection or systemic treatment. Detection rates and levels of ctDNA (digital droplet PCR) were correlated to tumor volume, relapse rate and survival. RESULTS: 60 patients with localized and 47 patients with metastatic PDAC were included. ctDNA was detected in 10% of localized and 57.4% of metastasized PDAC samples. In localized disease, ctDNA detection significantly correlated with the numbers of involved locoregional lymph nodes (p = 0.030). Primary tumor volume did not correlate with ctDNA levels in neither localized (p = 0.573) nor metastasized disease (p = 0.878). In disseminated disease, ctDNA levels correlated with total tumor volume (p = 0.026) and especially with liver metastases volume (p = 0.004), but not with other metastases. Detection of pretherapeutic ctDNA was associated with shorter DFS in localized (3.3 vs. 18.1 months, p = 0.000), whereas ctDNA levels were associated with worse survival in metastatic PDAC (5.7 vs. 7.8 months, p = 0.036). CONCLUSION: ctDNA positivity indicates major nodal involvement or even presence of undetected distant metastases associated with early recurrence in localized PDAC. Moreover, it predicts worse clinical outcome in both localized and metastatic disease.