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Purpose: This study evaluated the ability of F-FDG PET/CT imaging to predict early response to Y-radioembolization in comparison with contrast-enhanced CT (CECT) using RECIST and lesion density (Choi) criteria. Progression-free survival (PFS) in patients with liver metastases at 2 years and decline in tumour markers were the primary end-points of the study. Methods: A total of 121 liver lesions were evaluated in 25 patients (14 men, 11 women) with liver-dominant metastatic colorectal cancer who underwent F-FDG PET/CT and CECT before and 6-8 weeks after treatment. Changes in SUV, tumour density measured in terms of Hounsfield units and the sum of the longest diameters (LD) were calculated for the target liver lesions in each patient. The patient responses to treatment were categorized using EORTC PET criteria, tumour density criteria (Hounsfield units) and RECIST, and were correlated with the responses of tumour markers and 2-year PFS using Kaplan-Meier plots and the log-rank test for comparison. Multivariate proportional hazards (Cox) regression analysis was performed to assess the effect of relevant prognostic factors on PFS. Results: Using F-FDG PET/CT response criteria, 15 patients had a partial response (PR) and 10 patients had stable disease (SD), while using RECIST only 2 patients had a PR and 23 had SD. Two patients had a PR, 21 SD and 2 progressive disease using tumour density criteria. The mean changes in SUV, sum of the LDs and tumour density after treatment were 2.9 ± 2.6, 7.3 ± 14.4 mm and 1.9 ± 13.18 HU, respectively. Patients who had a PR on F-FDG PET/CT had a mean decrease of 44.5 % in SUV compared to those with SD who had a decrease of only 10.3 %. The decreases in SUV and sum of the LDs were significant ( p < 0.0001, p < 0.05, respectively) while the decrease in tumour density was not ( p > 0.1065). The responses on the F-FDG PET/CT studies were highly correlated with the responses of tumour markers ( p < 0.0001 for LDH, p = 0.01 for CEA and p = 0.02 for Ca19-9), while the responses on the CECT studies using both RECIST and tumour density criteria were not significantly correlated with the responses of tumour markers. The responses on F-FDG PET/CT studies also significantly predicted PFS (the median PFS in those with a PR was 12.0 months and in those with SD was 5 months, p < 0.0001), while RECIST and tumour density did not significantly predict PFS. Multivariate analysis demonstrated that responses on F-FDG PET/CT studies and decreases in SUV of ≤2.0 were the strongest predictors of PFS. Conclusion: Early response assessment to Y-radioembolization using F-FDG PET/CT is superior to RECIST and tumour density, demonstrating a correlation with tumour markers and significantly predicting PFS in patients with liver metastases. This could enable early response-adapted treatment strategies to be employed. [ABSTRACT FROM AUTHOR]

Resection is still the gold standard treatment for operable colorectal liver metastases. However, chemotherapy is likely to play an increasingly important role in the coming years. Many patients undergoing liver resection will eventually relapse, and adjuvant chemotherapy may help to reduce the risk of relapse. Furthermore, most patients with liver metastases present with unresectable lesions, and their chances of long-term survival are low. Neoadjuvant chemotherapy can reduce the size of the lesions, in some cases enabling them to be resected, thereby prolonging patient survival. A combination of pre- and post-operative chemotherapy may have enhanced effects on improving patient outcome, and this approach is currently being assessed. Until now, fluoropyrimidines have been the mainstay of treatment for metastatic colorectal cancer. Newer drugs, such as irinotecan, show higher activity and early reports suggest benefits in the treatment of liver metastases. [Copyright &y& Elsevier]

Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of pancreatic cancer for several decades. Early clinical trials of immunotherapy have yielded disappointing results proposing other means by which the tumour microenvironment serves to decrease the immune response. Additionally, the emergence of various subtypes of pancreatic cancer has emerged as a factor for treatment responses with immunogenic subtypes carrying a better prognosis. Herein we discuss the reasons for the poor response to checkpoint inhibitors and outline a rationale why combination treatments are likely to be most effective. We review the therapies which could provide optimal synergistic effects to immunotherapy including chemotherapy, agents targeting the stroma, co-stimulatory molecules, vaccinations and methods of immunogenic tumour priming including radiofrequency ablation. Finally, we discuss reasons why peri-operative and in particular neoadjuvant combination treatments are likely to be most effective and should be considered for early clinical trials. [ABSTRACT FROM AUTHOR]

• This ESMO Clinical Practice Guideline provides key recommendations for managing cancer of unknown primary (CUP). • The guideline covers CUP diagnosis, risk assessment, classification, treatment and follow-up. • Differential diagnostic algorithms for discrimination between CUP and other cancers are provided. • The author group includes multidisciplinary experts from different institutions in Europe, Australia and the United States. • Recommendations are based on available scientific data and the authors' collective expert opinion. • In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. Methods: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. Results: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P< 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1 -year OS: AUC 64% (95% CI 58-69)]. Conclusion: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers. [ABSTRACT FROM AUTHOR]

Presents case reports on myeloma and benign intracranial hypertension. Absence of association between intracranial hypertension and myeloma; Mechanism of benign intracranial hypertension; Relation between benign intracranial hypertension and overproduction of cerebrospinal fluid.

Background: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. Methods: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1–5 and 8–12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1–14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. Results: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0–23.7) with TT-B and 17.7 months (95% CI: 12.6–19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55–1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. Conclusions: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. Clinical trial information: NCT02743221 (clinicaltrials.gov) [ABSTRACT FROM AUTHOR]

We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT–B) and capecitabine plus bevacizumab (C–B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT–B (N = 77) or C–B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. Median (range) duration of treatment was 7.8 (6.0–9.7) months and 6.2 (4.1–9.1) months in the TT–B and C–B groups, respectively. Median (range) PFS was 9.2 (7.6–11.6) and 7.8 (5.5–10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT–B had more grade ≥3 neutropenia (47% versus 5% with C–B). Patients receiving C–B had more grade ≥3 hand–foot syndrome (12% versus 0% with TT–B) and grade ≥3 diarrhea (8% versus 1% with TT–B), consistent with the known safety profiles of these agents. TT–B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. NCT02743221 (ClinicalTrials.gov) • More effective treatment options are needed in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. • Trifluridin/tipiracil in monotherapy and in combination is an effective and well-tolerated option in mCRC. • Trifluridin/tipiracil plus bevacizumab is active and safe for patients with mCRC ineligible for first-line combination chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.Methods: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.Results: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70).Conclusions: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.Clinical Trial Registration: ISRCTN71070888; ClinialTrials.gov (NCT03529175). [ABSTRACT FROM AUTHOR]