Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine CisGem, improved the response rate, but did not improve the progression-free survival (PFS) ...in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes.
Changes in 15 circulating plasma angiogenesis or inflammatory-related proteins and cytokeratin-18 (CK18), measured at baseline and during therapy until disease progression, were correlated with overall survival (OS) using time-varying covariate Cox models (TVC).
Samples were available from n = 117/124 (94%) patients. Circulating Ang1&2, FGFb, PDGFbb, VEGFC, VEGFR1 and CK18 decreased as a result of the therapy, independent of treatment with cediranib. Circulating VEGFR2 and Tie2 were preferentially reduced by cediranib. Patients with increasing levels of VEGFA at any time had a worse PFS and OS; this detrimental effect was attenuated in patients receiving cediranib. TVC analysis revealed CK18 and VEGFR2 increases correlated with poorer OS in all patients (P < 0.001 and P = 0.02, respectively).
Rising circulating VEGFA levels in patients with ABC, treated with CisGem, are associated with worse PFS and OS, not seen in patients receiving cediranib. Rising levels of markers of tumour burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation.
Local treatment of metastases by surgical resection or other ablative therapies is technically feasible in an increasing number of patients with multi-organ metastatic cancer. This results in a ...growing debate on whether patients with extensive disease, that is traditionally deemed unresectable, may benefit from local treatment of metastases when added to standard palliative systemic therapy. For selected patients with oligometastatic colorectal cancer, local treatment of metastases has become the standard of care based on retrospective reports showing long-term survival rates. In addition to systemic therapy, preliminary evidence suggests that patients with extensive metastatic colorectal cancer may also benefit from local treatment. Here, we present the future perspectives based on the available literature on local treatment approaches in colorectal cancer.
•Local treatment of metastases is increasingly performed in patients with metastatic colorectal cancer (mCRC).•Resection of oligometastases in mCRC is a common practice.•Preliminary evidence shows survival benefit from tumour debulking in extensive mCRC.•Direct comparison of survival rates from the modern systemic therapy is yet to be made.
Cholangiocarcinoma (CCA) is associated with poor outcomes and limited treatment options, leading to increased use of targeted therapies for its management. Here, we performed one of the largest ...single-centre reviews evaluating outcomes following personalised targeted agents in CCA patients.
All consecutive CCA patients receiving systemic therapy between January 2010 and April 2023 at UCLH were included. The primary objective of this study was to evaluate treatment response, survival outcomes and predictors of clinical benefit in CCA patients treated with molecularly guided therapies. Patient demographic factors, disease characteristics and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional-hazards models.
Of the 227 consecutive CCA patients, 162 (71%) had molecular profiling, of whom 56 (35%) were eligible and 55 received molecular-targeted treatment. CCA histological classifications comprised intrahepatic (N = 32), extrahepatic (N = 11), hilar (N = 4) and unknown (N = 9) subtypes. Most patients received targeted agents based on genomic profiling in a second treatment line setting (N = 34). Frequently observed genomic alterations occurred in the
(N = 21),
(N = 7) and
(N = 6) genes. Median progression-free survival (PFS) following first-, second- and third-line systemic therapy and overall survival (OS) were 8.44 (95% CI, 7.49-12.78), 5.65 (95% CI, 3.71-7.13), 5.55 (2.79-12.58) and 29.01 (24.21-42.91) months, respectively. CCA subtype and FGFR/BRCA molecular aberration status were not associated with PFS or OS. However, a prior CCA-related surgical history was predictive of OS (
= 0.02). Stratification by best overall response to second-line targeted agents demonstrated an association with PFS (
= 0.002) and OS (
= 0.02). Duration of treatment with second-line targeted therapy was associated with OS (
< 0.001).
Patients receiving targeted therapeutics achieved promising outcomes, especially those attaining a favourable treatment response and those receiving targeted agents for longer periods. Liquid biopsies can reliably provide information on extended molecular profiling to aid patient selection for personalised therapies.
Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically ...unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH.
Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan-Meier approach. All analyses were adjusted for age, gender, and side of primary tumour.
One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19-89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months 95% Confidence Interval (CI) 21.5-29.0, and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12-0.29,
< 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival-with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank
< 0.0001). After exclusion of those who received systemic chemotherapy only (
= 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20-0.63,
< 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival.
Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness.
Abstract
Background
In those receiving chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. We aimed to develop a machine learning model to ...identify those patients that need closer monitoring, enabling a safer and more efficient service.
Methods
We used retrospective data from a large academic hospital, for patients treated with chemotherapy for breast cancer, colorectal cancer and diffuse‐large B‐cell lymphoma, to train and validate a Multi‐Layer Perceptrons (MLP) model to predict the outcomes of unacceptable rises in bilirubin or creatinine. To assess the performance of the model, validation was performed using patient data from a separate, independent hospital using the same variables. Using this dataset, we evaluated the sensitivity and specificity of the model.
Results
1214 patients in total were identified. The training set had almost perfect sensitivity and specificity of >0.95; the area under the curve (AUC) was 0.99 (95% CI 0.98–1.00) for creatinine and 0.97 (95% CI: 0.95–0.99) for bilirubin. The validation set had good sensitivity (creatinine: 0.60, 95% CI: 0.55–0.64, bilirubin: 0.54, 95% CI: 0.52–0.56), and specificity (creatinine 0.98, 95% CI: 0.96–0.99, bilirubin 0.90, 95% CI: 0.87–0.94) and area under the curve (creatinine: 0.76, 95% CI: 0.70, 0.82, bilirubin 0.72, 95% CI: 0.68–0.76).
Conclusions
We have demonstrated that a MLP model can be used to reduce the number of blood tests required for some patients at low risk of organ dysfunction, whilst improving safety for others at high risk.
Background:
This study aims to compare the outcomes of COVID-19-positive disease in patients with a
history of cancer to those without.
Methods:
We retrospectively collected clinical data and ...outcomes of COVID-19 positive cancer
patients treated consecutively in five North London hospitals (cohort A). Outcomes
recorded included time interval between most recent anti-cancer treatment and admission,
severe outcome a composite endpoint of intensive care unit (ITU) admission, ventilation
and/or death and mortality. Outcomes were compared with consecutively admitted COVID-19
positive patients, without a history of cancer (cohort B), treated at the primary centre
during the same time period (1 March–30 April 2020). Patients were matched for age,
gender and comorbidity.
Results:
The median age in both cohorts was 74 years, with 67% male, and comprised of 30
patients with cancer, and 90 without (1:3 ratio). For cohort B, 579 patients without a
history of cancer and consecutively admitted were screened from the primary London
hospital, 105 were COVID-19 positive and 90 were matched and included. Excluding cancer,
both cohorts had a median of two comorbidities. The odds ratio (OR) for mortality,
comparing patients with cancer to those without, was 1.05 95% confidence interval (CI)
0.4–2.5, and severe outcome (OR 0.89, 95% CI 0.4–2.0) suggesting no increased risk of
death or a severe outcome in patients with cancer. Cancer patients who received systemic
treatment within 28 days had an OR for mortality of 4.05 (95% CI 0.68–23.95),
p = 0.12. On presentation anaemia, hypokalaemia, hypoalbuminaemia and
hypoproteinaemia were identified predominantly in cohort A. Median duration of admission
was 8 days for cancer patients and 7 days for non-cancer.
Conclusion:
A diagnosis of cancer does not appear to increase the risk of death or a severe outcome
in COVID-19 patients with cancer compared with those without cancer. If a second spike
of virus strikes, rational decision making is required to ensure optimal cancer
care.
Personalized treatment approaches for patients with limited liver metastases from colorectal cancer are critically needed. By leveraging three large, independent cohorts of patients with colorectal ...liver metastases (n = 336), we found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases; however, high CIN70 scores generate a therapeutic vulnerability to DNA-damaging therapies leading to improved treatment responses. We propose CIN70 as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer. These findings are potentially broadly applicable to other human cancers.
ObjectivesFemale physicians in medicine are increasing, but disparities in female authorship exist. The aim of this study was to characterise factors associated with female first (FF) and female ...senior (SF) authorship in later phase systemic oncological clinical trials in biliary tract cancer (BTC) and identify any changes over time.SettingEmbase/Medline identified trial publications in BTC (2000–2020) were included. χ2 tests and log regression were used (assessed factors associated with FF and SF authorship, including changes over time (STATA V.16)).Primary outcome measureFF and SF authorship in later phase systemic oncological clinical trials in BTC.Secondary outcome measureAny changes over time?ResultsOf 501 publications, 163 met inclusion criteria. The median percentage of female author representation in publications was 25%; there were no female authors in 13% of publications. Geographic location of the home institution of the first and senior authors was Asia (42%/42%), Europe (29%/29%), USA (24%/22%) and other (4%/6%), respectively. Overall, FF and SF author representation was 20% and 10%, respectively. The median position of the first female author was second in all the publication author lists. The phase of trial, journal-impact factor, industry funding or whether the study met its primary endpoint did not impact FF/SF author representation. More SF authors had home institutions in ‘other’ geographic locations (40% in 10 trials) (p=0.02) versus Asia (6%), Europe (8%) and USA (14%). There were no significant changes in FF/SF representation over time (p=0.61 and p=0.33 respectively).ConclusionsFF and SF author representation in later phase systemic clinical trial publications in BTC is low and has not changed significantly over time. The underlying reasons for this imbalance need to be better understood and addressed.
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