Publications by authors named "Angela Lamarca"

123 Publications

Pancreatic Enzyme Replacement Therapy for Patients Diagnosed With Pancreaticobiliary Cancer: Validation of an Algorithm for Dose Escalation and Management.

Pancreas 2021 Oct;50(9):1254-1259

Dietetics, Manchester Royal Infirmary, Manchester, United Kingdom.

Objective: An algorithm was designed aiming to provide consistency of pancreatic enzyme replacement therapy (PERT) dosing/titration across healthcare professionals in pancreaticobiliary cancers (PBCs). This prospective observational study aimed to validate this algorithm.

Methods: Consecutive patients with inoperable or postoperative PBC with pancreatic exocrine insufficiency (PEI) symptoms, not taking PERT, or taking below the algorithm "starting dose," were eligible. A dietitian or clinical nurse specialist reviewed patients for up to 3 weeks, titrating PERT as per the algorithm. Feasibility of algorithm deliverability was assessed by the percentage of patients with successful completion (primary objective).

Results: Twenty-five patients were eligible (N = 25): at baseline, 22 took PERT (100% on suboptimal doses, 54.5% taking incorrectly) and 3 initiated PERT because of PEI symptoms. Algorithm completion (20 of 25, 80%) confirming deliverability by dietitians (11 of 12, 92%) and clinical nurse specialists (9 of 13, 69%). Symptom resolution occurred in 8 of 19 (42%), 3 of 7 (43%), and 1 of 3 (33%) patients at first, second, and third reviews, respectively; advice compliance was between 63% and 86%.

Conclusions: This algorithm provides a structured method to titrate PERT. At diagnosis, all patients with PBC should be assessed for PEI and adequate PERT initiated. Regular reviews are required for timely symptom resolution and adequate escalation, facilitating differential diagnosis if refractory symptoms exist.
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http://dx.doi.org/10.1097/MPA.0000000000001906DOI Listing
October 2021

Synoptic reporting of echocardiography in carcinoid heart disease (ENETS Carcinoid Heart Disease Task Force).

J Neuroendocrinol 2021 Nov 2:e13060. Epub 2021 Nov 2.

Royal Free Hospital & University College London, London, UK.

Background: This European Neuroendocrine Tumor Society (ENETS) Expert Consensus document aims to provide practical guidance and standardization for echocardiography in the screening and follow-up of carcinoid heart disease (CHD) in patients with a neuroendocrine tumour (NET) and carcinoid syndrome.

Methods: NET experts within the ENETS Carcinoid Heart Disease Task Force reviewed both general reporting guidelines and specialized scoring systems for transthoracic echocardiography (TTE) in CHD. Based on this review, a dedicated template report was designed by the multidisciplinary working group of cardiologists, oncologists, endocrinologists, gastroenterologists, surgeons and radiologists.

Results: We propose a Synoptic Reporting of Echocardiography in Carcinoid Heart Disease which represents an agreed peer reviewed proforma to capture information at the time of referral and enable a detailed outcome of CHD assessment. This includes a systematic and detailed list of structures to evaluate data to capture at the time of reporting of TTE.

Conclusions: Adherence to these reporting guidelines aims to promote homogeneous and detailed evaluation of CHD to secure accurate assessment and allow comparison of studies performed intra- and inter-individually. These guidelines could also facilitate CHD assessment as part of prospective clinical trials to enable standardization of the findings seen in response to therapy.
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http://dx.doi.org/10.1111/jne.13060DOI Listing
November 2021

Potential influence of the microbiome environment in patients with biliary tract cancer and implications for therapy.

Br J Cancer 2021 Oct 18. Epub 2021 Oct 18.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.

Biliary tract cancers, including intra- and extra-hepatic cholangiocarcinoma as well as gallbladder cancer, are associated with poor prognosis and the majority of patients present with advanced-stage, non-resectable disease at diagnosis. Biliary tract cancer may develop through an accumulation of genetic and epigenetic alterations and can be influenced by microbial exposure. Furthermore, the liver and biliary tract are exposed to the gastrointestinal microbiome through the gut-liver axis. The availability of next-generation sequencing technology has led to an increase in studies investigating the relationship between microbiota and human disease. In particular, the interplay between the microbiome, the tumour micro-environment and response to systemic therapy is a prospering area of interest. Given the poor outcomes for patients with biliary tract cancer, this emerging field of research, through which new biomarkers may be identified, offers potential as a tool for early diagnosis, prognostication or even as a future therapeutic target. This review summarises the available evidence on the microbiome environment in patients with biliary tract cancer, including a discussion around confounding factors, implications for therapy and proposed future directions.
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http://dx.doi.org/10.1038/s41416-021-01583-8DOI Listing
October 2021

Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis.

Cancer Treat Rev 2021 Dec 11;101:102299. Epub 2021 Oct 11.

University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK. Electronic address:

Background: Gastroenteropancreatic neoplasms (GEP-NENs)can potentially be cured through surgical resection, but only 42-57% achieve 5-year disease-free survival.There is a lack of consensus regarding the factorsassociated withrelapse followingresection ofGEP-NENs.

Methods: Asystematic review identified studies reporting factors associated with relapse in patients with GEP-NENs following resection of a primary tumour. Meta-analysis was performed to identify the factors prognostic for relapse-free survival (RFS)oroverall survival (OS).

Results: 63 studies comprising 13,715 patients were included; 56 studies reported on pancreatic NENs (12,418 patients), 24 reported on patients with grade 1-2 tumours (4,735 patients). Median follow-up was 44.2 months, median RFS was 32 months. Pooling of multivariable analyses of GEP-NENs (all sites and grades) found the following factors predicted worse RFS (all p values < 0.05): vascular resection performed, metastatic disease resected, grade 2 disease, grade 3 disease, tumour size > 20 mm, R1 resection, microvascular invasion, perineural invasion, Ki-67 > 5% and any lymph node positivity. In a subgroup of studies comprising exclusively of grade 1-2 GEP-NENs, R1 resection, perineural invasion, grade 2 disease, any lymph node positivity and tumour size > 20 mm predicted worse RFS (all p values < 0.05). Few OSdata were available for pooling; in univariableanalysis(entire cohort), grade 2 predicted worse OS (p = 0.007), whileR1 resectiondid not (p = 0.14).

Conclusions: The factors prognostic for worse RFS following resection of a GEP-NEN identified in this meta-analysis could be included in post-curative treatment surveillance clinical guidelines and inform the stratification and inclusion criteria of future adjuvant trials.
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http://dx.doi.org/10.1016/j.ctrv.2021.102299DOI Listing
December 2021

Pancreaticobiliary Malignancies in the Emergency Room: Management of Acute Complications and Oncological Emergencies.

J Gastrointest Cancer 2021 Oct 14. Epub 2021 Oct 14.

Leeds Institute of Medical Research, St James' Institute of Oncology, St James' University Hospital, University of Leeds, Leeds, LS9 7TF, UK.

Background: Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions.

Methods: Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented.

Results: The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented.

Conclusion: Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals' expectations.
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http://dx.doi.org/10.1007/s12029-021-00718-7DOI Listing
October 2021

Potential utility of liquid biopsies in the management of patients with biliary tract cancers: A review.

World J Gastrointest Oncol 2021 Sep;13(9):1073-1085

Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom.

Biliary tract cancer, comprising gallbladder cancer, cholangiocarcinoma and ampullary cancer, represents a more uncommon entity outside high-endemic areas, though global incidence is rising. The majority of patients present at a late stage, and 5-year survival remains poor. Advanced stage disease is incurable, and though palliative chemotherapy has been shown to improve survival, further diagnostic and therapeutic options are required in order to improve patient outcomes. Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations, attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness. Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic, predictive and prognostic biomarkers. In this review, the current standard of care for patients with biliary tract cancer, future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed. Circulating tumour DNA, circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer. A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.
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http://dx.doi.org/10.4251/wjgo.v13.i9.1073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465442PMC
September 2021

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Cancers (Basel) 2021 Aug 18;13(16). Epub 2021 Aug 18.

Division of Cancer Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester M13 9PL, UK.

Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in "real-world" treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, = 0.015; and disease control rate; 59.7% vs. 79.6%, = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, = 0.016) and overall survival (OS) (adjusted-HR = 1.640, = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (<55% vs. ≥55%) had significantly different PFS (adjusted- = 0.021) and OS (adjusted- = 0.051), with the non-SC subgroup with a Ki-67 index of <55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.
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http://dx.doi.org/10.3390/cancers13164152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392018PMC
August 2021

Druggable molecular alterations in bile duct cancer: potential and current therapeutic applications in clinical trials.

Expert Opin Investig Drugs 2021 Sep 22;30(9):975-983. Epub 2021 Aug 22.

Department Of Medical Oncology, Centre Eugène Marquis, Rennes, France, France.

: Cholangiocarcinomas (CCA) are rare tumors that are associated with a variety of molecular alterations. Many of these alterations are now actionable using drugs currently in development, and CCA may be a perfect example of application of a precision oncology approach. However, development of drugs in CCA faces the challenge of targeting rare alterations in a rare disease.: In this review, we present the current data on targeted therapies in development for CCA, focusing on and alterations. We also discuss rationale for targeting other alterations, currently without specific development in CCA. We searched PubMed and google scholar in February 2021 for relevant articles and presentation in recent congress regarding the literature on molecular alterations, drugs in cholangiocarcinomas and biliary tract cancers.: Despite a strong rationale and promising early results, applying a precision oncology approach in CCA for everyday patients is still exposed to significant challenges: obtaining the molecular portrait of these tumors due to difficulties with biopsy access, complexities of drug development in subgroups of these relatively rare tumors, and sub-optimal access to drugs outside clinical trials.
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http://dx.doi.org/10.1080/13543784.2021.1964470DOI Listing
September 2021

The Microbiome as a Potential Target for Therapeutic Manipulation in Pancreatic Cancer.

Cancers (Basel) 2021 Jul 27;13(15). Epub 2021 Jul 27.

Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.
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http://dx.doi.org/10.3390/cancers13153779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345056PMC
July 2021

Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity.

Cancer Cell 2021 Sep 22;39(9):1227-1244.e20. Epub 2021 Jul 22.

Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK. Electronic address:

Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition of 18 murine tissues and 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals extensive stromal heterogeneity across tissues and tumors, and identifies coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. Expression of CD105 demarks two stable and functionally distinct pancreatic fibroblast lineages, which are also identified in murine and human healthy tissues and tumors. Whereas CD105-positive pancreatic fibroblasts are permissive for tumor growth in vivo, CD105-negative fibroblasts are highly tumor suppressive. This restrictive effect is entirely dependent on functional adaptive immunity. Collectively, these results reveal two functionally distinct pancreatic fibroblast lineages and highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth.
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http://dx.doi.org/10.1016/j.ccell.2021.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443274PMC
September 2021

Locoregional therapies in patients with intrahepatic cholangiocarcinoma: A systematic review and pooled analysis.

Cancer Treat Rev 2021 Sep 7;99:102258. Epub 2021 Jul 7.

Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, Manchester, United Kingdom.

Background: Locoregional treatments (LRT) including radioembolisation (SIRT), transarterial chemo-embolisation (TACE), hepatic arterial infusion (HAI) of chemotherapy, external beam radiotherapy (EBRT) and ablation have been studied for the management of intrahepatic cholangiocarcinoma (iCC). The aim of this systematic review was to provide outcome benchmarks for clinical trial design.

Methods: Identification of studies reporting outcomes of patients treated with LRT for iCC was performed using PubMed and Embase. Pooled weighted means were calculated for progression-free survival (PFS) and overall survival (OS); meta-analysis of proportions was used for estimation of pooled response rate.

Results: 6325 entries were reviewed; 93 studies were eligible, representing 101 cohorts and 3990 patients: 15 cohorts (645 patients) for ablation, 18 cohorts (541 patients) for EBRT, 27 cohorts (1232 patients) for SIRT, 22 cohorts (1145 patients) for TACE, 16 cohorts (331 patients) for HAI and 3 cohorts (96 patients) not pooled. 74% of the studies were retrospective, 99% non-randomised. The pooled mean weighted OS was 30.2 months (95% confidence interval (CI): 21.8-38.6) for ablation, 18.9 (14.2-23.5) for EBRT, 14.1 (12.1-16.0) for SIRT, 15.9 (12.9-19.0) for TACE and 21.3 (15.4-27.1) for HAI. The pooled complete response rate was 93.9% for ablation. When analysed together, SIRT, TACE and HAI had a pooled mean weighted OS of 15.7 months, and 25.2 months for patients treated in first-line with concomitant systemic chemotherapy.

Conclusions: Available literature on LRT for iCC was heterogeneous and of insufficient quality to make strong recommendations. Ablation achieved satisfactory outcomes, and may be recommended when surgery is not feasible.
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http://dx.doi.org/10.1016/j.ctrv.2021.102258DOI Listing
September 2021

Second-line FOLFOX chemotherapy for advanced biliary tract cancer - Authors' reply.

Lancet Oncol 2021 07;22(7):e288-e289

Department of Medical Oncology, The Christie NHS Foundation Trust/Institute of Cancer Sciences, University of Manchester, Manchester M20 4BX,, UK; Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(21)00341-7DOI Listing
July 2021

Antiproliferative Systemic Therapies for Metastatic Small Bowel Neuroendocrine Tumours.

Curr Treat Options Oncol 2021 06 29;22(8):73. Epub 2021 Jun 29.

The Christie NHS Foundation Trust, Wilmslow Road, M20 4BX, Manchester, UK.

Opinion Statement: Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies with rising incidence and prevalence. Outcome and therapy of small bowel neuroendocrine tumours (SBNETs) is variable, depending on the grade, differentiation, tumour burden, as well as the site of the tumour origin. Because of this, multidisciplinary approach is essential. Large randomized clinical trials, with somatostatin analogues (PROMID, CLARINET) or with peptide receptor radionuclide therapy (PRRT) with 177-lutetium (NETTER-1 trial) as well as the mammalian target of rapamycin inhibitor (mTOR) everolimus (RADIANT trials), represent milestones for the medical management of unresectable grade 1 and 2 SBNETS over the last decade. Novel therapies, such as tyrosine kinase inhibitors (TKI), are on the cutting edge. However, multiple unsolved questions remain. This review provides a comprehensive review of the main systemic therapeutic options for advanced SBNETs and discusses the latest guideline recommendations for palliative treatment.
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http://dx.doi.org/10.1007/s11864-021-00863-yDOI Listing
June 2021

The Impact of Gallium DOTA PET/CT in Managing Patients With Sporadic and Familial Pancreatic Neuroendocrine Tumours.

Front Endocrinol (Lausanne) 2021 7;12:654975. Epub 2021 Jun 7.

Barts and the London HPB Centre, Royal London Hospital, London, United Kingdom.

Objective: Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of Gallium (Ga)-DOTA PET/CT in managing patients with panNETs.

Design: A retrospective study conducted across three tertiary UK NET referral centres.

Methods: Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a Ga-DOTA PET/CT scan for a suspected panNET.

Results: We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 9.3% (n=163 vs. 17) alive dead (3 data missing), 141 sporadic 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional functional tumours comprised 73.2 21.3% (n=134 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224 Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall, Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases.

Conclusion: Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease.
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http://dx.doi.org/10.3389/fendo.2021.654975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215358PMC
June 2021

Treatment outcomes of advanced digestive well-differentiated grade 3 NETs.

Endocr Relat Cancer 2021 Jun 23;28(8):549-561. Epub 2021 Jun 23.

Université de Paris, Department of Pathology, Beaujon/Bichat University Hospital (APHP), Clichy/Paris, France.

There is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied. Pathological samples were centrally reviewed, and radiological data were locally reviewed. We analyzed RECIST-defined objective response (OR), tumor growth rate (TGR) and progression-free survival (PFS) obtained with first- (L1) or second-line (L2) treatments. We included 74 patients with advanced G3 NETs, mostly from the duodenal or pancreatic origin (71.6%), with median Ki-67 of 30%. The 126 treatments (L1 = 74; L2 = 52) included alkylating-based (n = 32), etoposide-platinum (n = 22) or adenocarcinoma-like (n = 20) chemotherapy, somatostatin analogs (n = 21), targeted therapies (n = 22) and liver-directed therapies (n = 7). Alkylating-based chemotherapy achieved the highest OR rate (37.9%) compared to other treatments (multivariable OR 4.22, 95% CI (1.5-12.2); P = 0.008). Adenocarcinoma-like and alkylating-based chemotherapies showed the highest reductions in 3-month TGR (P < 0.001 and P = 0.008, respectively). The longest median PFS was obtained with adenocarcinoma-like chemotherapy (16.5 months (9.0-24.0)) and targeted therapies (12.0 months (8.2-15.8)), while the shortest PFS was observed with somatostatin analogs (6.2 months (3.8-8.5)) and etoposide-platinum chemotherapy (7.2 months (5.2-9.1)). Etoposide-platinum CT achieved shorter PFS than adenocarcinoma-like (multivariable HR 3.69 (1.61-8.44), P = 0.002) and alkylating-based chemotherapies (multivariable HR 1.95 (1.01-3.78), P = 0.049). Overall, adenocarcinoma-like and alkylating-based chemotherapies may be the most effective treatments for patients with advanced G3 NETs regarding OR and PFS. Etoposide-platinum chemotherapy has poor efficacy in this setting.
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http://dx.doi.org/10.1530/ERC-21-0109DOI Listing
June 2021

Clinical benefit of surveillance after resection of pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Eur J Surg Oncol 2021 Sep 10;47(9):2248-2255. Epub 2021 May 10.

Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address:

Background: The value of routine surveillance after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear, and expert guidelines offer conflicting recommendations. This study is a systematic review of evidence for surveillance programs.

Methods: A systematic review of studies evaluating different surveillance methods was undertaken. A meta-analysis was performed for those studies reporting rates of asymptomatic recurrence, treatment of recurrence and overall survival, according to different surveillance methods.

Results: Ten studies were included in the literature review, with five studies appropriate for meta-analysis (1596 patients). Patients within active surveillance programs were more likely to have recurrence detected at an asymptomatic stage (Pooled Rate: 49.3% vs. 19.1%, p = 0.043). Within studies reporting these outcomes, patients with asymptomatic recurrence were more likely to receive treatment for recurrence (Odds Ratio 3.49; 95% CI: 1.73-7.07; p < 0.001) and had longer overall survival (Mean Difference: 9.5 months; 95% CI: 4.1-14.8; p < 0.001) than those with symptoms at time of recurrence.

Discussion: Routine surveillance after surgery for PDAC appears to detect more patients at an asymptomatic stage. Data from these non-randomised trials also suggest that treatment rates and survival may be superior in patients were recurrence is detected when asymptomatic. As such, these data suggest that routine surveillance may improve patient outcomes, although an appropriately conducted trial would be required to address concerns that various sources of bias may be affecting these results.
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http://dx.doi.org/10.1016/j.ejso.2021.04.031DOI Listing
September 2021

REPLY.

Hepatology 2021 Oct 21;74(4):2319-2321. Epub 2021 Aug 21.

Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, United Kingdom.

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http://dx.doi.org/10.1002/hep.31904DOI Listing
October 2021

Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol.

BMJ Open 2021 05 13;11(5):e042067. Epub 2021 May 13.

Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK

Introduction: Pancreatic exocrine insufficiency (PEI) in patients with pancreatic malignancy is well documented in the literature and is known to negatively impact on overall survival and quality of life. A lack of consensus opinion remains on the optimal diagnostic test that can be adapted for use in a clinical setting for this cohort of patients. This study aims to better understand the prevalence of PEI and the most suitable diagnostic techniques in patients with advanced pancreatic malignancy.

Methods And Analysis: This prospective observational study will be carried out in patients with pancreatic malignancy (including adenocarcinoma and neuroendocrine neoplasms). Consecutive patients with inoperable pancreatic malignancy referred for consideration of first-line chemotherapy will be considered for eligibility. The study comprises three cohorts: demographic cohort (primary objective to prospectively investigate the prevalence of PEI in patients with inoperable pancreatic malignancy); sample size 50, diagnostic cohort (primary objective to design and evaluate an optimal diagnostic panel to detect PEI in patients with inoperable pancreatic malignancy); sample size 25 and follow-up cohort (primary objective to prospectively evaluate the proposed PEI diagnostic panel in a cohort of patients with inoperable pancreatic malignancy); sample size 50. The following is a summary of the protocol and methodology.

Ethics And Dissemination: Full ethical approval has been granted by the North West Greater Manchester East Research and Ethics Committee, reference: 17/NW/0597. This manuscript reflects the latest protocol V.8 approved 21 April 2020. Findings will be disseminated by presentation at national/international conferences, publication in peer-review journals and distribution via patient advocate groups.

Trial Registration Number: 194255, NCT0361643.
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http://dx.doi.org/10.1136/bmjopen-2020-042067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126274PMC
May 2021

Systemic therapies in elderly patients with advanced hepatocellular carcinoma: do not forget metronomic capecitabine.

Eur J Surg Oncol 2021 08 3;47(8):2209-2210. Epub 2021 May 3.

Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.

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http://dx.doi.org/10.1016/j.ejso.2021.04.015DOI Listing
August 2021

Lenvatinib in Patients With Advanced Grade 1/2 Pancreatic and Gastrointestinal Neuroendocrine Tumors: Results of the Phase II TALENT Trial (GETNE1509).

J Clin Oncol 2021 07 4;39(20):2304-2312. Epub 2021 May 4.

Osteoncology and Rare Tumours Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Purpose: Approved systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have shown limited capacity to reduce tumor burden and no antitumor activity after progression to targeted agents (TAs). We investigated the efficacy and safety of lenvatinib in patients with previously treated advanced GEP-NETs.

Patients And Methods: This was a multicenter, single-arm, open-label, phase II trial with two parallel cohorts (ClinicalTrials.gov identifier: NCT02678780) involving 21 institutions in 4 European countries. Eligible patients had histologically confirmed advanced grade 1-2 pancreatic (panNET) or GI (GI-NET) NETs with documented tumor progression after treatment with a TA (panNET) or somatostatin analogs (GI-NET). Patients were treated with lenvatinib 24 mg once daily until disease progression or treatment intolerance. The primary end point was overall response rate by central radiology review. Secondary end points included progression-free survival, overall survival, duration of response, and safety.

Results: Between September 2015 and March 2017, a total of 111 patients were enrolled, with 55 (panNET) and 56 (GI-NET) patients in each cohort. The median follow-up was 23 months. The overall response rate was 29.9% (95% CI, 21.6 to 39.6): 44.2% (panNET) and 16.4% (GI-NET). The median (range) duration of response was 19.9 (8.4-30.8) and 33.9 (10.6-38.3) months in the panNET and GI-NET groups, respectively. The median progression-free survival was 15.7 months (95% CI, 14.1 to 19.5). The most common adverse events were fatigue, hypertension, and diarrhea; 93.7% of patients required dose reductions or interruptions.

Conclusion: We report the highest centrally confirmed response reported to date with a multikinase inhibitor in advanced GEP-NETs, with a particularly strong response in the panNET cohort. This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other TAs, suggesting the potential value of lenvatinib in the treatment of advanced GEP-NETs.
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http://dx.doi.org/10.1200/JCO.20.03368DOI Listing
July 2021

Chemotherapy for advanced gallbladder cancer (GBC): A systematic review and meta-analysis.

Crit Rev Oncol Hematol 2021 Jul 20;163:103328. Epub 2021 Apr 20.

Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, United Kingdom; Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. Electronic address:

Background: The benefit from chemotherapy, specifically for patients with gallbladder cancer (GBC), has been poorly explored since GBC is mostly studied jointly with other biliary tract cancers (BTC).

Methods: Eligible studies reporting outcome of palliative systemic chemotherapy for advanced GBC were identified through MEDLINE, cross-referencing and conferences (PROSPERO-CRD42019155745). Meta-analysis of proportions and calculation of pooled weighted means were performed.

Results: 58 eligible studies (n = 1,986 patients); cisplatin/gemcitabine (33 % of patients), gemcitabine/oxaliplatin (14 %) or gemcitabine monotherapy (9%). Estimated pooled overall radiological response rate(ORR), and pooled weighted mean progression-free (PFS) and overall survivals (OS) were 23.2 % (95 %-CI 20.0-26.5) (I: 52.5 % (p < 0.001)), 4.8 months (95 %-CI 4.3-5.2) and 8.3 months (95 %CI 7.6-8.9), respectively. Patients with non-GBC BTCs achieved a lower ORR than GBC [odds ratio 0.65 (95 % CI, 0.50-0.84)].

Conclusions: GBC benefit from chemotherapy differs from other BTCs, with shorter PFS/OS despite higher ORR; new treatment options are urgently required for management of advanced GBC.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103328DOI Listing
July 2021

Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial.

Lancet Oncol 2021 05 30;22(5):690-701. Epub 2021 Mar 30.

Department of Medical Oncology, The Christie NHS Foundation Trust/Institute of Cancer Sciences, University of Manchester, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK. Electronic address:

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer.

Methods: The ABC-06 clinical trial was a phase 3, open-label, randomised trial done in 20 sites with expertise in managing biliary tract cancer across the UK. Adult patients (aged ≥18 years) who had histologically or cytologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line cisplatin and gemcitabine chemotherapy and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) centrally to active symptom control (ASC) and FOLFOX or ASC alone. FOLFOX chemotherapy was administered intravenously every 2 weeks for a maximum of 12 cycles (oxaliplatin 85 mg/m, L-folinic acid 175 mg [or folinic acid 350 mg], fluorouracil 400 mg/m [bolus], and fluorouracil 2400 mg/m as a 46-h continuous intravenous infusion). Randomisation was done following a minimisation algorithm using platinum sensitivity, serum albumin concentration, and stage as stratification factors. The primary endpoint was overall survival, assessed in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. The study is complete and the final results are reported. This trial is registered with ClinicalTrials.gov, NCT01926236, and EudraCT, 2013-001812-30.

Findings: Between March 27, 2014, and Jan 4, 2018, 162 patients were enrolled and randomly assigned to ASC plus FOLFOX (n=81) or ASC alone (n=81). Median follow-up was 21·7 months (IQR 17·2-30·8). Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4-7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1-5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50-0·97]; p=0·031). The overall survival rate in the ASC alone group was 35·5% (95% CI 25·2-46·0) at 6 months and 11·4% (5·6-19·5) at 12 months, compared with 50·6% (39·3-60·9) at 6 months and 25·9% (17·0-35·8) at 12 months in the ASC plus FOLFOX group. Grade 3-5 adverse events were reported in 42 (52%) of 81 patients in the ASC alone group and 56 (69%) of 81 patients in the ASC plus FOLFOX group, including three chemotherapy-related deaths (one each due to infection, acute kidney injury, and febrile neutropenia). The most frequently reported grade 3-5 FOLFOX-related adverse events were neutropenia (ten [12%] patients), fatigue or lethargy (nine [11%] patients), and infection (eight [10%] patients).

Interpretation: The addition of FOLFOX to ASC improved median overall survival in patients with advanced biliary tract cancer after progression on cisplatin and gemcitabine, with a clinically meaningful increase in 6-month and 12-month overall survival rates. To our knowledge, this trial is the first prospective, randomised study providing reliable, high-quality evidence to allow an informed discussion with patients of the potential benefits and risks from second-line FOLFOX chemotherapy in advanced biliary tract cancer. Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials.

Funding: Cancer Research UK, StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity), and The Christie Charity, with additional funding from The Cholangiocarcinoma Foundation and the Conquer Cancer Foundation Young Investigator Award for translational research.
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http://dx.doi.org/10.1016/S1470-2045(21)00027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082275PMC
May 2021

Advanced small-bowel well-differentiated neuroendocrine tumours: An international survey of practice on 3-line treatment.

World J Gastroenterol 2021 Mar;27(10):976-989

Medical Oncology Department, The Ramón y Cajal Health Research Institute, Alcalá University, University Hospital Ramon y Cajal, Madrid 28034, Spain.

Background: Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence.

Aim: To understand current practice and rationale for decision-making by physicians in the 3-line setting by building an online survey.

Methods: Weighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored.

Results: Replies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4).

Conclusion: Everolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.
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http://dx.doi.org/10.3748/wjg.v27.i10.976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968134PMC
March 2021

Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis.

Cancer Treat Rev 2021 Mar 19;94:102168. Epub 2021 Feb 19.

Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. Electronic address:

Objective: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.

Methods: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .

Results: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.

Conclusions: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.
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http://dx.doi.org/10.1016/j.ctrv.2021.102168DOI Listing
March 2021

Ivosidenib: an investigational drug for the treatment of biliary tract cancers.

Expert Opin Investig Drugs 2021 Apr 26;30(4):301-307. Epub 2021 Apr 26.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester/Department of Medical Oncology, the Christie NHS Foundation Trust, Manchester, UK.

: Biliary tract cancers (BTCs) [including cholangiocarcinoma and gallbladder cancer] are rare cancers associated with poor survival; most patients have advanced disease at diagnosis. Current chemotherapy reference regimens include cisplatin and gemcitabine as first-line; and oxaliplatin and 5-fluorouracil (FOLFOX) in second-line. Molecular profiling has identified several actionable therapeutic targets including isocitrate dehydrogenase (IDH)1 mutations. Ivosidenib is a reversible inhibitor of mutant IDH1; it is currently approved for the treatment of acute myeloid leukemia and has been studied in patients with advanced cholangiocarcinoma.: This article introduces current treatments for BTC and sheds light on the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of ivosidenib in advanced cholangiocarcinoma. The authors conclude with insights on the changing treatment paradigm created by emerging drugs and precision approaches.: Ivosidenib is well tolerated, with good oral exposure and long half-life as shown by phase I data. In a phase III study, ivosidenib has demonstrated improved progression-free survival compared to placebo (median 2.7 vs 1.4 months; hazard ratio 0.37; 95% confidence interval 0.25-0.54; one-sided p < 0.0001); it has also demonstrated a trend toward increased overall survival in patients with cholangiocarcinoma and disease progression on prior chemotherapy. Final survival data from this study are pending presentation. Increased use of molecular profiling will continue to identify potential therapeutic targets and improve the prognosis of patients with these cancers.
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http://dx.doi.org/10.1080/13543784.2021.1900115DOI Listing
April 2021

Targeted therapies for extrahepatic cholangiocarcinoma: preclinical and clinical development and prospects for the clinic.

Expert Opin Investig Drugs 2021 Apr 23;30(4):377-388. Epub 2021 Feb 23.

Department of Molecular Medicine (DMM), University of Padua, Padua. Italy.

Until recently, cholangiocarcinoma (CCA) was a largely overlooked disease, and among CCAs, extrahepatic CCA (eCCA) was even more neglected. Despite the growing impact of molecularly targeted therapies and immunotherapy, prognosis of eCCA is dismal. Therefore, unraveling the complex molecular landscape of eCCA has become an urgent need. Deep phenotyping studies have revealed that eCCA is a heterogeneous tumor, harboring specific alterations categorizable into four classes, 'Mesenchymal', 'Proliferation', 'Immune', 'Metabolic'. Molecular alterations convey the activation of several pro-oncogenic pathways, where either actionable drivers or outcome predictors can be identified. We offer insights on perturbed pathways, molecular profiling, and actionable targets in eCCA and present a perspective on the potential stepping-stones to future progress. A systematic literature search in PubMed/ClinicalTrials.gov websites was performed by authors from different disciplines according to their specific topic knowledge to identify the newest and most relevant advances in precision medicine of eCCA. eCCA is a distinct entity with unique features in terms of molecular classes, oncogenic drivers, and tumor microenvironment. Since more prevalent mutations are currently undruggable, and immunotherapy can be offered only to a minority of patients, international collaborations are instrumental to improve the understanding of the molecular underpins of this disease.
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http://dx.doi.org/10.1080/13543784.2021.1880564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194059PMC
April 2021

REPLY.

Hepatology 2021 Aug 10;74(2):1129-1131. Epub 2021 Aug 10.

Medical Oncology/Institute of Cancer Sciences, The Christie NHS Foundation Trust/University of Manchester, Manchester, United Kingdom.

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http://dx.doi.org/10.1002/hep.31740DOI Listing
August 2021

External validity of somatostatin analogues trials in advanced neuroendocrine neoplasms: the GETNE-TRASGU study.

Neuroendocrinology 2021 Jan 28. Epub 2021 Jan 28.

Introduction: Somatostatin analogues (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NETs.

Methods: We identified patients with well-differentiated (Ki67% ≤20%), metastatic GEP-NETs treated in first-line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real world clinical practice versus RCTs.

Results: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki67% was 4 (range: 0-20). The most common primary tumor sites were: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n=266) and half, lanreotide autogel (n=269). The median PFS was 28.0 months (95% CI, 22.1-32.0) for octreotide vs 30.1 months (95% CI, 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide vs octreotide was 0.90 (95% credible interval, 0.71-1.12). The probability of effect sizes >30% with lanreotide vs octreotide was 2% and 6% for midgut and foregut NENs, respectively.

Conclusion: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data).. Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.
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http://dx.doi.org/10.1159/000514808DOI Listing
January 2021

The Potential Role of Liquid Biopsies in Advancing the Understanding of Neuroendocrine Neoplasms.

J Clin Med 2021 Jan 21;10(3). Epub 2021 Jan 21.

Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.

Tumour tissue as a source for molecular profiling and for in vivo models has limitations (e.g., difficult access, limited availability, single time point, potential heterogeneity between primary and metastatic sites). Conversely, liquid biopsies provide an easily accessible approach, enabling timely and longitudinal interrogation of the tumour molecular makeup, with increased ability to capture spatial and temporal intra-tumour heterogeneity compared to tumour tissue. Blood-borne biomarker assays (e.g., circulating tumour cells (CTCs), circulating free/tumour DNA (cf/ctDNA)) pose unique opportunities for aiding in the molecular characterisation and phenotypic subtyping of neuroendocrine neoplasms and will be discussed in this article.
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http://dx.doi.org/10.3390/jcm10030403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865482PMC
January 2021
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