Publications by authors named "Florian Lordick"

254 Publications

[Gastric Cancer: diagnosis and current treatment strategies].

Dtsch Med Wochenschr 2021 Nov 26;146(23):1533-1537. Epub 2021 Nov 26.

Universitäres Krebszentrum Leipzig (UCCL).

Gastric and esophago-gastric junction (EGJ) adenocarcinoma are leading causes of cancer mortality and morbidity worldwide. In this short update article, we outline novel key developments in this field. Molecular defined subtypes can guide treatment decisions and create a roadmap for development of future agents in distinct subgroups of gastric cancer. In locally advanced EGJ cancer chemo-radiotherapy or perioperative chemotherapy are recommended treatment strategies. The FLOT regimen has evolved as a new standard for perioperative chemotherapy due to improved survival outcomes. For gastric cancer with limited metastasis, multimodality treatment approaches are under investigation. Systemic treatment over several lines along with best supportive care represents a standard in the management of metastatic disease. First line treatment should include trastuzmab in case of Her2 positivity. Immune checkpoint inhibitors are very effective in microsatellite instable tumors even in late treatment lines. In perspective, checkpoint inhibitors hold promise to become part of the standard treatment in the near future and novel Her2 targeted treatment approaches currently under development show promising results.
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http://dx.doi.org/10.1055/a-1169-0440DOI Listing
November 2021

Survival after secondary liver resection in metastatic colorectal cancer: Comparing data of three prospective randomized European trials (LICC, CELIM, FIRE-3).

Int J Cancer 2021 Nov 22. Epub 2021 Nov 22.

Medical Department, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

Metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) have a chance of long-term survival and potential cure after hepatic metastasectomy. However, the appropriate postoperative treatment strategy is still controversial. The CELIM and FIRE-3 studies demonstrated that secondary hepatic resection significantly improved overall survival (OS). The objective of this analysis was to compare these favorable outcome data with recent results from the LICC trial investigating the antigen-specific cancer vaccine tecemotide (L-BLP25) as adjuvant therapy in mCRC patients with LLD after R0/R1 resection. Data from mCRC patients with LLD and secondary hepatic resection from each study were analyzed for efficacy outcomes based on patient characteristics, treatment and surveillance after surgery. In LICC, 40/121 (33%) patients, in CELIM 36/111 (32%) and in FIRE-3-LLD 29/133 (22%) patients were secondarily resected, respectively. Of those, 31 (77.5%) patients in LICC and all patients in CELIM were R0 resected. Median disease-free survival after resection was 8.9 months in LICC, 9.9 months in CELIM. Median OS in secondarily resected patients was 66.1 months in LICC, 53.9 months in CELIM and 56.2 months in FIRE-3-LLD. Median age was about 5 years less in LICC compared to CELIM and FIRE-3. Secondarily resected patients of LICC, CELIM and FIRE-3 showed an impressive median survival with a tendency for improved survival for patients in the LICC trial. A younger patient cohort but also more selective surgery, improved resection techniques, deep responses and a close surveillance program after surgery in the LICC trial may have had a positive impact on survival.
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http://dx.doi.org/10.1002/ijc.33881DOI Listing
November 2021

Pathological complete response after neoadjuvant treatment determines survival in esophageal squamous cell carcinoma patients (NEOCRTEC5010).

Ann Transl Med 2021 Oct;9(20):1516

Department of Cardiothoracic Surgery, New York University Langone Health, New York, NY, USA.

Background: Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC.

Methods: All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR.

Results: Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates.

Conclusions: pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.
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http://dx.doi.org/10.21037/atm-21-3331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576689PMC
October 2021

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

J Gastrointestin Liver Dis 2021 Nov 8. Epub 2021 Nov 8.

Magdeburg, Germany.

Background And Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC.

Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire.

Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001).

Conclusions: In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.
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http://dx.doi.org/10.15403/jgld-3795DOI Listing
November 2021

Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin.

J Clin Oncol 2021 Nov 9:JCO2102008. Epub 2021 Nov 9.

Department of Quantitative Health Science, Mayo Clinic, Rochester, MN.

Purpose: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years).

Materials And Methods: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered.

Results: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% 80%, < .01), similar T stage (% T1-3/T4: 76/24 77/23, = .97), higher N2 disease rate (24% 22%, < .01), more likely to complete the planned treatment duration (83.2% 78.2%, < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; value < .001) and higher 5-year cancer-specific mortality rate (24% 20%; HR 1.21; 95% CI, 1.00 to 1.47; value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% 56%; HR 0.97; 95% CI, 0.73 to 1.29; value = .85).

Conclusion: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
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http://dx.doi.org/10.1200/JCO.21.02008DOI Listing
November 2021

Update on optimal management for pancreatic cancer: expert perspectives from members of the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty.

Expert Rev Anticancer Ther 2021 Nov 23:1-13. Epub 2021 Nov 23.

Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, Australia.

Introduction: Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localized and advanced pancreatic cancer and offers an expert opinion on current best practice.

Areas Covered: For patients with localized disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable, and locally advanced disease. Advances in metastatic disease are discussed including cytotoxic chemotherapy, targeted therapies, and the role of genomic testing to identify patients with molecular alterations. Reviewed literature included journal publications, abstracts presented at major international oncology meetings, and ongoing clinical trials databases.

Expert Opinion: Pancreatic cancer is a devastating diagnosis and despite recent advances has a very poor prognosis. Only a minority of patients, 20%, are diagnosed with potentially curable disease. The shifting paradigm toward neoadjuvant therapy may improve resectability and survival rates; however, robust evidence is required. Thus far, there has only been limited progress in advanced stage disease. Genomic testing may potentially identify more treatment targets although limited to small subgroups.
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http://dx.doi.org/10.1080/14737140.2022.2002689DOI Listing
November 2021

Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View.

Cancers (Basel) 2021 Oct 18;13(20). Epub 2021 Oct 18.

Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, 04103 Leipzig, Germany.

Gastric cancer is a leading cause of cancer death worldwide. Systemic treatment comprising chemotherapy and targeted therapy is the standard of care in advanced/metastatic gastric cancer. Comprehensive molecular characterization of gastric adenocarcinomas by the TCGA Consortium and ACRG has resulted in the definition of distinct molecular subtypes. These efforts have in parallel built a basis for the development of novel molecularly stratified treatment approaches. Based on this molecular characterization, an increasing number of specific genomic alterations can potentially serve as treatment targets. Consequently, the development of promising compounds is ongoing. In this review, key molecular alterations in gastric and gastroesophageal junction cancers will be addressed. Finally, the current status of the translation of targeted therapy towards clinical applications will be reviewed.
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http://dx.doi.org/10.3390/cancers13205216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533881PMC
October 2021

Biomarkers related to fatty acid oxidative capacity are predictive for continued weight loss in cachectic cancer patients.

J Cachexia Sarcopenia Muscle 2021 Oct 11. Epub 2021 Oct 11.

Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany.

Background: Cachexia is characterized by a negative protein and energy balance leading to loss of adipose tissue and muscle mass. Cancer cachexia negatively impacts treatment tolerability and prognosis. Supportive interventions should be initiated as early as possible. Biomarkers for early prediction of continuing weight loss during the course of disease are currently lacking.

Methods: In this pilot, observational, cross-sectional, case-control study, cachectic cancer patients undergoing systemic first-line cancer treatment were matched 2:1 with healthy controls according to age, gender and body mass index. Alterations in amino acid and energy metabolism, as indicated by acylcarnitine levels, were analysed using mass spectrometry in plasma samples (PS) and dried blood specimen (DBS). Welch's two-sample t-test was used for comparative analysis of metabolites between cancer patients and healthy matched controls and to identify the metabolomic profiles related to weight loss across different time points. A linear regression model was applied to correlate weight loss and single metabolites as predictor variables. Finally, metabolite pathway enrichment analyses were performed.

Results: Eighteen cases (14 male and 4 female) and 36 paired controls were enrolled. There was a good correlation between baseline PS and DBS of healthy controls for the levels of most amino acids but not for acylcarnitine. Amino acid levels related to cancer metabolism were significantly altered in cancer patients compared with controls in both DBS and PS for arginine, citrulline, histidine and ornithine and in DBS only for asparagine, glutamine, methylhistidine, methionine, ornithine, serine, threonine and leucine/isoleucine. Metabolite enrichment analysis in PS of cancer patients revealed histidine metabolism activation (P = 0.0025). Baseline acylcarnitine analysis in DBS was indicative for alterations of the mitochondrial carnitine shuttle, related to β-oxidation: The ratio palmitoylcarnitine/acylcarnitine (Q2) and the ratio palmitoylcarnitine + octadecenoylcarnitine/acylcarnitine (Q3) were predictive for early weight loss (P < 0.0001) and weight loss during follow-up. Activation of tryptophan metabolism (P = 0.035) in DBS and PS and activation of serine/glycine metabolism (P = 0.017) in PS were also related to early weight loss and across successive time points.

Conclusions: We found alterations in amino acid levels most likely attributable to cancer metabolism itself in cancer patients compared with controls. Baseline DBS represent a valuable analyte to study energy metabolism related to cancer cachexia. Acylcarnitine patterns (Q2, Q3) predicted further weight loss in cachectic cancer patients undergoing systemic therapy, and pathway analyses indicated involvement of the serine/glycine and the tryptophan pathway in this condition. Validation in larger cohorts is warranted.
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http://dx.doi.org/10.1002/jcsm.12817DOI Listing
October 2021

Adjuvant Chemotherapy for Stage I Pancreatic Ductal Adenocarcinoma-Is It Based on Evidence or Clinical Wisdom?

JAMA Oncol 2021 Oct 7. Epub 2021 Oct 7.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy.

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http://dx.doi.org/10.1001/jamaoncol.2021.3603DOI Listing
October 2021

Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition.

Cell Death Discov 2021 Sep 25;7(1):264. Epub 2021 Sep 25.

Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103, Leipzig, Germany.

Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients' responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation.
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http://dx.doi.org/10.1038/s41420-021-00651-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464600PMC
September 2021

Predictors for thromboembolism in patients with cholangiocarcinoma.

J Cancer Res Clin Oncol 2021 Sep 9. Epub 2021 Sep 9.

Department of Medicine (Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases), University Cancer Center Leipzig (UCCL), University of Leipzig Medical Center, Leipzig, Germany.

Background: Patients with cancer are at increased risk of thromboembolic events contributing significantly to cancer-related morbidity and mortality. Because cholangiocarcinoma is a rare type of cancer, the incidence of thromboembolism in this patient population is not well defined.

Methods: Patients with cholangiocarcinoma treated at the University Cancer Center Leipzig between January 2014 and December 2018 were analyzed retrospectively regarding the incidence of arterial and venous thromboembolism.

Results: A total of 133 newly and consecutively diagnosed patients were included, of whom 22% had stage IV disease. Thromboembolism was diagnosed in 39 (29.3%), with 48% of the events occurring between 60 days prior and 30 days after the initial diagnosis. Arterial thrombosis accounted for 19% and portal venous thrombosis for 33% of the events, while the rest of events occurred in the non-portal venous system. In multivariable analysis, an ONKOTEV score ≥ 2 was the only independent predictor for thromboembolism. Serum CA 19-9 was available in 87 patients (65.4%). In this subgroup, CA 19-9 above the median of 97.7 U/ml and vascular or lymphatic compression were independent predictors for thromboembolism in the first year and CA 19-9 alone remained a significant predictor over the whole observation period. An ONKOTEV score ≥ 2 and increasing age were predictors of survival.

Conclusions: A very high thromboembolic risk was observed in cholangiocarcinoma, comparable to the risk situation in pancreatic and gastric cancer. The ONKOTEV score and serum CA 19-9 are independent predictors of thromboembolic events. Prospective validation of our observations in this patient population is warranted.
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http://dx.doi.org/10.1007/s00432-021-03794-1DOI Listing
September 2021

Biomarker evaluation in radically resectable locally advanced gastric cancer treated with neoadjuvant chemotherapy: an evidence reappraisal.

Ther Adv Med Oncol 2021 1;13:17588359211029559. Epub 2021 Sep 1.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, via Ripamonti 435, Milan, Lombardia 20141, Italy.

Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice. We performed a narrative review, including 23 studies, addressing the value of tissue- or blood-based biomarkers in the neoadjuvant setting. Ten studies (43.5%) were prospective, and more than half were conducted in East-Asia. Biomarkers were evaluated only post-NAC (on surgical samples or blood) in seven studies (30.4%), only pre-NAC (on endoscopic specimens or blood) in 10 studies (43.5%), and both pre- and post-NAC (26.1%) in six studies. Among the high variety of investigated biomarkers, some of these including MSI-H or enzymatic profile (as TS, UGT1A1, MTHFR, ERCC or XRCC) showed promising results and deserve to be assessed in methodologically sound clinical trials. The identification of molecular biomarkers in patients treated with NAC for locally advanced resectable gastric or EGJ cancer remains crucial.
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http://dx.doi.org/10.1177/17588359211029559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414610PMC
September 2021

PD-1 inhibition in patient derived tissue cultures of human gastric and gastroesophageal adenocarcinoma.

Oncoimmunology 2021 18;10(1):1960729. Epub 2021 Aug 18.

Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany.

Emerging immunotherapies quest for better patient stratification in cancer treatment decisions. Moderate response rates of PD-1 inhibition in gastric and esophagogastric junction cancers urge for meaningful human model systems that allow for investigating immune responses . Here, the standardized patient-derived tissue culture (PDTC) model was applied to investigate tumor response to the PD-1 inhibitor Nivolumab and the CD3/CD28 t-lymphocyte activator ImmunoCult. Resident t-lymphocytes, tumor proliferation and apoptosis, as well as bulk gene expression data were analyzed after 72 h of PD-1 inhibition either as monotherapy or combined with Oxaliplatin or ImmunoCult. Individual responses to PD-1 inhibition were found and combination with chemotherapy or t-lymphocyte activation led to enhanced antitumoral effects in PDTCs. T-lymphocyte activation as well as the addition of pre-cultured peripheral blood mononuclear cells improved PDTC for studying t-lymphocyte and tumor cell communication. These data support the potential of PDTC to investigate immunotherapy in gastric and esophagogastric junction cancer.
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http://dx.doi.org/10.1080/2162402X.2021.1960729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381835PMC
October 2021

Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy.

Int J Mol Sci 2021 Jul 27;22(15). Epub 2021 Jul 27.

Department of Dermatology, Venereology and Allergology, University Medical Center Leipzig, Philipp-Rosenthal-Str. 23, 04103 Leipzig, Germany.

To identify potential early biomarkers of treatment response and immune-related adverse events (irAE), a pilot immune monitoring study was performed in stage IV melanoma patients by flow cytometric analysis of peripheral blood mononuclear cells (PBMC). Overall, 17 patients were treated with either nivolumab or pembrolizumab alone, or with a combination of nivolumab and ipilimumab every three weeks. Of 15 patients for which complete response assessment was available, treatment responders ( = 10) as compared to non-responders ( = 5) were characterized by enhanced PD-1 expression on CD8 T cells immediately before treatment (median ± median absolute deviation/MAD 26.7 ± 10.4% vs. 17.2 ± 5.3%). Responders showed a higher T cell responsiveness after T cell receptor ex vivo stimulation as determined by measurement of programmed cell death 1 (PD-1) expression on CD3 T cells before the second cycle of treatment. The percentage of CD8 effector memory (CD8CD45RACD45ROCCR7) T cells was higher in responders compared to non-responders before and immediately after the first cycle of treatment (median ± MAD 39.2 ± 7.3% vs. 30.5 ± 4.1% and 37.7 ± 4.6 vs. 24.0 ± 6.4). Immune-related adverse events (irAE) were accompanied by a higher percentage of activated CD4 (CD4CD38HLADR) T cells before the second treatment cycle (median ± MAD 14.9 ± 3.9% vs. 5.3 ± 0.4%). In summary, PBMC immune monitoring of immune-checkpoint inhibition (ICI) treatment in melanoma appears to be a promising approach to identify early markers of treatment response and irAEs.
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http://dx.doi.org/10.3390/ijms22158017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348898PMC
July 2021

Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients.

Front Oncol 2021 7;11:682088. Epub 2021 May 7.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany.

Background: About five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival.

Methods: For assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; = 53) and 2007 to 2018 (cohort 2; = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan-Meier plots and Cox regression.

Results: In cohort 2, the standardized processes (regular use of [F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries ( = 0.026) mostly located in the oropharynx ( = 0.001). From 66.0 to 87.1% increased ND frequency ( = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% ( = 0.411) and 66.1% ( = 0.025).

Conclusions: Standardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P.
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http://dx.doi.org/10.3389/fonc.2021.682088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138574PMC
May 2021

Targeted and immunotherapy in the era of personalised gastric cancer treatment.

Best Pract Res Clin Gastroenterol 2021 Mar-Apr;50-51:101738. Epub 2021 Feb 21.

Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Centre Leipzig (UCCL), Leipzig University Medical Centre, Leipzig, Germany. Electronic address:

Gastric cancer is a major cause of cancer-related morbidity and mortality worldwide. Advances in targeted medical treatment were scarce in the past and challenged by the marked spatial and temporal biological heterogeneity of gastric cancer. Recent molecular profiling studies have increased our understanding of genetic and epigenetic drivers, leading to better patient selection for drug development. Beyond that, immune-related biomarkers were identified, paving the way for future effective immunotherapy. We systematically reviewed articles from PubMed of the past 10 years, and abstracts from annual meetings of ESMO, ASCO and AACR to summarise the current knowledge about targeted and immunotherapy and outline pathways to future personalised therapy of gastric cancer.
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http://dx.doi.org/10.1016/j.bpg.2021.101738DOI Listing
May 2021

Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm.

Nat Rev Clin Oncol 2021 08 31;18(8):473-487. Epub 2021 Mar 31.

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Advances in cancer biology and sequencing technology have enabled the selection of targeted and more effective treatments for individual patients with various types of solid tumour. However, only three molecular biomarkers have thus far been demonstrated to predict a response to targeted therapies in patients with gastric and/or gastro-oesophageal junction (G/GEJ) cancers: HER2 positivity for trastuzumab and trastuzumab deruxtecan, and microsatellite instability (MSI) status and PD-L1 expression for pembrolizumab. Despite this lack of clinically relevant biomarkers, distinct molecular subtypes of G/GEJ cancers have been identified and have informed the development of novel agents, including receptor tyrosine kinase inhibitors and monoclonal antibodies, several of which are currently being tested in ongoing trials. Many of these trials include biomarker stratification, and some include analysis of circulating tumour DNA (ctDNA), which both enables the noninvasive assessment of biomarker expression and provides an indication of the contributions of intratumoural heterogeneity to response and resistance. The results of these studies might help to optimize the selection of patients to receive targeted therapies, thus facilitating precision medicine approaches for patients with G/GEJ cancers. In this Review, we describe the current evidence supporting the use of targeted therapies in patients with G/GEJ cancers and provide guidance on future research directions.
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http://dx.doi.org/10.1038/s41571-021-00492-2DOI Listing
August 2021

HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study.

J Clin Oncol 2021 05 25;39(13):1468-1478. Epub 2021 Mar 25.

University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany.

Purpose: Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC.

Methods: Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, gene expression was assessed using qPCR.

Results: Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2- mGC (20.5 months, n = 60 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab.

Conclusion: Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of expression and amplification levels may improve selection of patients for HER2-directed treatment.
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http://dx.doi.org/10.1200/JCO.20.02761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099392PMC
May 2021

Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma.

Gastric Cancer 2021 May 23;24(3):721-730. Epub 2021 Mar 23.

Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany.

Background: Zolbetuximab plus first-line EOX (epirubicin, oxaliplatin, capecitabine; ZOL/EOX) significantly prolonged progression-free survival and overall survival in the FAST trial vs EOX alone. We report the patient-reported outcomes (PROs) of FAST in patients with advanced gastroesophageal adenocarcinoma.

Methods: Patients were randomized to ZOL/EOX or EOX alone. Patients could receive ≤ 8 EOX cycles and remained on zolbetuximab until disease progression. PROs were collected using the EORTC QLQ-C30 and QLQ-STO22 before drug administration at day 1/cycle 1, day 1/cycle 5, end of EOX treatment, and q12w thereafter until disease progression. Time to deterioration (TTD), defined as the first meaningful worsening from baseline, in the individual QLQ-C30/QLQ-STO22 scores was analyzed. Longitudinal changes in scores from baseline were analyzed using a mixed-effects model for repeated measures (MMRM).

Results: The per protocol population included 143 (ZOL/EOX: 69; EOX: 74) patients. Baseline QLQ-C30 and STO22 scores were comparable between arms and denoted intermediate-to-high quality of life (QoL), intermediate-to-low global health status (GHS) and low symptom burden. Descriptive analyses showed no differences between arms until end of EOX but maintenance therapy with zolbetuximab was associated with better QoL and less symptom burden thereafter. TTD for most scores favored ZOL/EOX over EOX and reached statistical significance for GHS (p = 0.008). MMRM results support TTD findings; no statistically significant differences were observed between arms in any score except for nausea and vomiting (p = 0.0181 favoring EOX).

Conclusions: ZOL/EOX allowed patients to maintain good QoL and low symptom burden for longer than EOX alone.
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http://dx.doi.org/10.1007/s10120-020-01153-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064997PMC
May 2021

Psychosocial aftercare of adolescent and young adult cancer survivors in Germany: Awareness, utilisation, satisfaction and associated factors.

Psychooncology 2021 08 25;30(8):1311-1321. Epub 2021 Mar 25.

Department of Mental Health, Medical Psychology & Medical Sociology, University of Leipzig, Leipzig, Germany.

Aim: This study systematically assesses the awareness of, utilisation of and satisfaction with psychosocial care for adolescents and young adult (AYA) cancer survivors in aftercare.

Methods: Survivors between 18 and 39 years were surveyed in aftercare. Awareness of, utilisation of and satisfaction with psychological counselling (PC), social-legal counselling (SLC) and other psychosocial care (OPC) were measured using self-developed questionnaires. Multivariate analyses were conducted to determine factors correlated with awareness and use of psychosocial care.

Results: Five hundred and fourteen survivors participated; the mean age at diagnosis was 29.6 years (SD = 6.14). 54% of cancer survivors were aware of PC, 45% of SLC and 24% of OPC. Those who possessed knowledge about these services used it to a considerable extent (63%-74%), and the majority (66%-75%) was highly satisfied. No common factors could be found that increase the likelihood of being aware of these three services (R  = 0.028-0.138). Female gender (OR = 2.08-2.18) and high anxiety (OR = 1.19-1.38) were identified as common factors that increase the likelihood of utilising psychosocial services (R  = 0.160-0.395).

Conclusion: AYA who are aware of psychosocial services in aftercare are motivated to use them and express high satisfaction with use. For the utilisation of psychosocial services, anxiety and female gender can be identified as common factors. The visibility of psychosocial services for aftercare should be increased given the high number of unaware AYA survivors. The active and repeated addressing of psychosocial issues and regular provision of information (e.g., written guides on survivorship) by caregivers should be made a standard of care for AYA cancer survivors.
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http://dx.doi.org/10.1002/pon.5678DOI Listing
August 2021

Symptom Burden and Palliative Care Needs of Patients with Incurable Cancer at Diagnosis and During the Disease Course.

Oncologist 2021 06 30;26(6):e1058-e1065. Epub 2021 Mar 30.

Leipzig University Medical Center, University Cancer Center Leipzig, Leipzig, Germany.

Background: Although current guidelines advocate early integration of palliative care, symptom burden and palliative care needs of patients at diagnosis of incurable cancer and along the disease trajectory are understudied.

Material And Methods: We assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer in a prospective longitudinal observational multicenter study. Patients were evaluated using validated self-report measures (National Comprehensive Cancer Network Distress Thermometer [DT], Functional Assessment of Cancer Therapy [FACT], Schedule for the Evaluation of Individual Quality of Life [SEIQoL-Q], Patients Health Questionnaire-4 [PHQ-4], modified Supportive Care Needs Survey [SCNS-SF-34]) at baseline (T0) and at 3 (T1), 6 (T2), and 12 months (T3) follow-up.

Results: From October 2014 to October 2016, 500 patients (219 women, 281 men; mean age 64.2 years) were recruited at 20 study sites in Germany following diagnosis of incurable metastatic, locally advanced, or recurrent lung (217), gastrointestinal (156), head and neck (55), gynecological (57), and skin (15) cancer. Patients reported significant distress (DT score ≥ 5) after diagnosis, which significantly decreased over time (T0: 67.2%, T1: 51.7%, T2: 47.9%, T3: 48.7%). The spectrum of reported symptoms was broad, with considerable variety between and within the cancer groups. Anxiety and depressiveness were most prevalent early in the disease course (T0: 30.8%, T1: 20.1%, T2: 14.7%, T3: 16.9%). The number of patients reporting unmet supportive care needs decreased over time (T0: 71.8 %, T1: 61.6%, T2: 58.1%, T3: 55.3%).

Conclusion: Our study confirms a variable and mostly high symptom burden at the time of diagnosis of incurable cancer, suggesting early screening by using standardized tools and underlining the usefulness of early palliative care.

Implications For Practice: A better understanding of symptom burden and palliative care needs of patients with newly diagnosed incurable cancer may guide clinical practice and help to improve the quality of palliative care services. The results of this study provide important information for establishing palliative care programs and related guidelines. Distress, symptom burden, and the need for support vary and are often high at the time of diagnosis. These findings underscore the need for implementation of symptom screening as well as early palliative care services, starting at the time of diagnosis of incurable cancer and tailored according to patients' needs.
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http://dx.doi.org/10.1002/onco.13751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176980PMC
June 2021

FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo.

Cancers (Basel) 2021 Feb 25;13(5). Epub 2021 Feb 25.

Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.

Diagnosis in an advanced state is a major hallmark of ovarian cancer and recurrence after first line treatment is common. With upcoming novel therapies, tumor markers that support patient stratification are urgently needed to prevent ineffective therapy. Therefore, the transcription factor FOXM1 is a promising target in ovarian cancer as it is frequently overexpressed and associated with poor prognosis. In this study, fresh tissue specimens of 10 ovarian cancers were collected to investigate tissue cultures in their ability to predict individual treatment susceptibility and to identify the benefit of FOXM1 inhibition. FOXM1 inhibition was induced by thiostrepton (3 µM). Carboplatin (0.2, 2 and 20 µM) and olaparib (10 µM) were applied and tumor susceptibility was analyzed by tumor cell proliferation and apoptosis in immunofluorescence microscopy. Resistance mechanisms were investigated by determining the gene expression of FOXM1 and its targets BRCA1/2 and RAD51. Ovarian cancer tissue was successfully maintained for up to 14 days ex vivo, preserving morphological characteristics of the native specimen. Thiostrepton downregulated FOXM1 expression in tissue culture. Individual responses were observed after combined treatment with carboplatin or olaparib. Thus, we successfully implemented a complex tissue culture model to ovarian cancer and showed potential benefit of combined FOXM1 inhibition.
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http://dx.doi.org/10.3390/cancers13050956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956612PMC
February 2021

CRBP-TS - evaluation of a home-based training and health care program for colorectal, breast, and prostate cancer using telemonitoring and self-management: study protocol for a randomized controlled trial.

BMC Sports Sci Med Rehabil 2021 Feb 23;13(1):15. Epub 2021 Feb 23.

Institute of Sport Medicine and Prevention, University Leipzig, Marschnerstraße 29a, 04109, Leipzig, Germany.

Background: Physical training is recommended in various national and international guidelines for patients with cancer. Observational studies have shown that physical activity leads to reduced recurrence and mortality rates by 20-40% in colorectal, breast, and prostate cancer. Despite existing evidence, a systematic care structure is still lacking. The primary aim of this study is to implement and evaluate an online training platform to strengthen physical performance and patient empowerment after cancer surgery.

Methods: The evaluation will be conducted as a prospective multicenter randomized controlled trial with three subgroups (colorectal-, breast-, and prostate cancer). Each group will include 100 patients (total 300 patients including dropouts; clinical stages T1-3 and/or N+; M0 after surgery intervention) and the primary endpoint (13% increase in the maximal oxygen consumption during exercise) will be examined. The intervention group will receive a 6-month home-based online training (2-3 times per week strength-endurance training using video presentations), bidirectional activity feedback information, online communication, and online counseling. The control group (usual care) will be advised lifestyle improvement. In-hospital testing will be performed before, during, and after the intervention. In addition to cardiopulmonary capacity, tumor specific diagnostics (liquid biopsy, depression and fatigue assessment, metabolic and endothelial screening) will be applied.

Discussion: Due to the increasing incidence of cancer, associated with considerable mortality, morbidity and impaired quality of life, there is an imperative requirement for improved cancer care, of which structured physical training may become an integral component.

Trial Registration: DRKS-ID: DRKS00020499 ; Registered 17 March 2020.
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http://dx.doi.org/10.1186/s13102-021-00244-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901214PMC
February 2021

Covid-19 in outpatients-Is fever a useful indicator for SARS-CoV-2 infection?

PLoS One 2021 3;16(2):e0246312. Epub 2021 Feb 3.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.

Objective: Understanding mild to moderate symptoms of coronavirus disease 2019 (Covid-19) is important in order to identify active cases early and thus counteract transmission.

Methods: In March 2020, Leipzig University Hospital established an outpatient clinic for patients potentially infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Confirmed cases with mild to moderate symptoms self-isolated at home and were followed-up by daily telephone calls for at least 14 days. Symptoms and course of illness of these patients are reported here.

Results: From March 20 to April 17, 2020, 1460 individuals were tested for SARS-CoV-2 by naso- or oropharyngeal swab for real-time polymerase chain reaction (RT-PCR). Covid-19 was confirmed in 91 (6.2%) patients, of which 87 were included in the final analysis. Patients presented for testing after a mean of 5.9 days (IQR = 2.0-8.5). The median age was 37.0 years (IQR = 28.5-53), and 48 (55.2%) were female. Five (5.7%) patients required hospital admission during the course of illness. Most frequently reported symptoms were fatigue (n = 64, 74%), cough (n = 58, 67%), and hyposmia/hypogeusia (n = 44, 51%). In contrast to previous reports, fever occurred in less than a third of patients (n = 25, 29%). By day 14, more than half of the patients had recovered completely (n = 37/70, 52.9%).

Conclusions: Fever seems to be less common in patients of relatively young age diagnosed with mild to moderate Covid-19. This suggests that body temperature alone may be an insufficient indicator of SARS-CoV-2 infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246312PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857607PMC
February 2021

Anti-PD1 monotherapy in hepatocellular carcinoma: a step forward or already behind?

Ann Transl Med 2020 Dec;8(24):1701

Department of Medicine-II (Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases), University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany.

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http://dx.doi.org/10.21037/atm-20-4438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812228PMC
December 2020

SATB1-Mediated Upregulation of the Oncogenic Receptor Tyrosine Kinase HER3 Antagonizes MET Inhibition in Gastric Cancer Cells.

Int J Mol Sci 2020 Dec 23;22(1). Epub 2020 Dec 23.

Clinical Pharmacology, Rudolf-Boehm-Institute for Pharmacology and Toxicology, Medical Faculty, Leipzig University, D-04107 Leipzig, Germany.

MET-amplified gastric cancer cells are extremely sensitive to MET inhibition in vitro, whereas clinical efficacy of MET inhibitors is disappointing. The compensatory activation of other oncogenic growth factor receptors may serve as an underlying mechanism of resistance. In this study, we analyzed the role of HER receptors, in particular HER3 and its ligand heregulin, in this respect. This also included the chromatin-organizer protein SATB1, as an established regulator of HER expression in other tumor entities. In a panel of MET-amplified gastric carcinoma cell lines, cell growth under anchorage-dependent and independent conditions was studied upon inhibitor treatment or siRNA-mediated knockdown. Expression analyses were performed using RT-qPCR, FACS, and immunoblots. Signal transduction was monitored via antibody arrays and immunoblots. As expected, MET inhibition led to a growth arrest and inhibition of MAPK signaling. Strikingly, however, this was accompanied by a rapid and profound upregulation of the oncogenic receptor HER3. This finding was determined as functionally relevant, since HER3 activation by HRG led to partial MET inhibitor resistance, and MAPK/Akt signaling was even found enhanced upon HRG+MET inhibitor treatment compared to HRG alone. SATB1 was identified as mediator of HER3 upregulation. Concomitantly, SATB1 knockdown prevented upregulation of HER3, thus abrogating the HRG-promoted rescue from MET inhibition. Taken together, our results introduce the combined HER3/MET inhibition as strategy to overcome resistance towards MET inhibitors.
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http://dx.doi.org/10.3390/ijms22010082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796274PMC
December 2020

Toward a Routine Assessment of Visceral Adipose Tissue Volume from Computed Tomographic Data.

Obesity (Silver Spring) 2021 02 25;29(2):294-301. Epub 2020 Dec 25.

Department of Diagnostic and Interventional Radiology, Leipzig University Hospital, Leipzig, Germany.

Objective: The study's aim was to determine to what extent total visceral adipose tissue (VAT) volume (V ) measured from segmented VAT areas (A ) on all axial computed tomography (CT) sections (thickness of 5 mm) between the diaphragm and pelvic floor can be predicted by the A of commonly selected landmark sections in patients with overweight or obesity.

Methods: A total of 113 patients (31 females, 82 males) with images of full abdominopelvic coverage and proper image quality were included (BMI = 25.0-64.1 kg/m , 29.5 ± 4.9 kg/m ). Linear regression between A and V (reference) was used to determine approximate equations for VAT volume for all parameters (single sex, different anatomical landmarks or lumbar intervertebral disc spaces, one or five axial sections). Agreement was evaluated by the multivariate coefficient of determination and by the SD of the percentage difference (s ) between the estimated VAT volume on one or five sections and V .

Results: The V was 0.9 to 8.4 (3.8 ± 2.2) L for females and 2.7 to 11.7 (5.6 ± 2.1) L for males. Best agreement was found at L2-3 (s  = 14.3%-15.5%) for females and at L1-2 or L2-3 (11.7%-12.4%) for males. Agreement at the umbilicus or the femoral heads was poor (20.2%-57.9%). Segmentation of one or five sections was substantially faster (11/70 seconds) than whole-abdomen processing (15 minutes).

Conclusions: V can be rapidly estimated by VAT segmentation of axial CT sections at sex-specific lumbar intervertebral disc spaces.
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http://dx.doi.org/10.1002/oby.23061DOI Listing
February 2021

Impact of COVID-19 on cancer service delivery: results from an international survey of oncology clinicians.

ESMO Open 2020 12;5(6):e001090

Sir Peter MacCallum Department of Oncology, University of Melbourne Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Electronic address:

Objectives: To report clinician-perceived changes to cancer service delivery in response to COVID-19.

Design: Multidisciplinary Australasian cancer clinician survey in collaboration with the European Society of Medical Oncology.

Setting: Between May and June 2020 clinicians from 70 countries were surveyed; majority from Europe (n=196; 39%) with 1846 COVID-19 cases per million people, Australia (AUS)/New Zealand (NZ) (n=188; 38%) with 267/236 per million and Asia (n=75; 15%) with 121 per million at time of survey distribution.

Participants: Medical oncologists (n=372; 74%), radiation oncologists (n=91; 18%) and surgical oncologists (n=38; 8%).

Results: Eighty-nine per cent of clinicians reported altering clinical practices; more commonly among those with versus without patients diagnosed with COVID-19 (n=142; 93% vs n=225; 86%, p=0.03) but regardless of community transmission levels (p=0.26). More European clinicians (n=111; 66.1%) had treated patients diagnosed with COVID-19 compared with Asia (n=20; 27.8%) and AUS/NZ (n=8; 4.8%), p<0.001. Many clinicians (n=307; 71.4%) reported concerns that reduced access to standard treatments during the pandemic would negatively impact patient survival. The reported proportion of consultations using telehealth increased by 7.7-fold, with 25.1% (n=108) of clinicians concerned that patient survival would be worse due to this increase. Clinicians reviewed a median of 10 fewer outpatients/week (including non-face to face) compared with prior to the pandemic, translating to 5010 fewer specialist oncology visits per week among the surveyed group. Mental health was negatively impacted for 52.6% (n=190) of clinicians.

Conclusion: Clinicians reported widespread changes to oncology services, in regions of both high and low COVID-19 case numbers. Clinician concerns of potential negative impacts on patient outcomes warrant objective assessment, with system and policy implications for healthcare delivery at large.
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http://dx.doi.org/10.1136/esmoopen-2020-001090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709494PMC
December 2020
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