The Influence of Long-Acting Somatostatin Analogs on 68 Ga-DOTATATE Uptake in Patients With Neuroendocrine Tumors

Purpose A high SUVmax tumor-to-liver ratio (TLR) of 68Ga-DOTATATE can be used to select patients with neuroendocrine tumors (NETs) for peptide receptor radionuclide therapy (PRRT). In addition, an SUVmax TLR ≥ 8.1 is associated with increased progression-free survival in NET patients treated with somatostatin analogs (SSAs). To avoid a theoretical interaction, several guidelines recommend performing PET/CT just before the monthly administration of long-acting SSAs. We aimed to investigate the effect of SSA on the SUVmax of 68Ga-DOTATATE in patients with NET and to identify independent predictors for high SUVmax TLR. Patients and Methods For this retrospective study, 192 68Ga-DOTATATE PET/CT scans of 165 patients without (n = 115) and with (n = 77) SSA (octreotide or lanreotide) in the 3 months before PET/CT were collected and reviewed. The effect of SSA on SUVmax values was analyzed by a maximum likelihood mixed model. Results Patients with SSA had a significantly higher median SUVmax TLR than patients without SSA (4.7 [IQR], 3.1-7.7) versus 3.2 [IQR, 2.0-5.4]; P < 0.001). Multivariable logistic regression analysis showed that SSA use was an independent predictor for SUVmax TLR ≥ 8.1 (odds ratio, 2.91; 95% confidence interval, 1.26-6.72; P = 0.012). Conclusions Our data suggest that higher SSA concentrations do not have a negative effect on 68Ga-DOTATATE uptake in tumor lesions. In addition, we found that only SSA use was associated with SUVmax TLR ≥ 8.1. Our results are consistent with previously conducted studies and in line with the recently published guideline that suggests that the relatively recent use of SSA does not necessitate any delay in 68Ga-DOTATATE PET/CT imaging

A critical appraisal of the potential benefit of post-operative structured follow-up after resection for biliary tract cancer

BACKGROUND: There is currently no evidence to support structured use of imaging or biomarkers during follow-up of patients after curative resection of biliary tract cancer (BTC). Besides, the influence of early detection of recurrence and subsequent start of palliative chemotherapy on overall survival remains unknown. The aim of this study is to describe and compare the results of two follow-up strategies. METHODS: This retrospective multicenter cohort study compared patients from the Amsterdam UMC undergoing pragmatic clinical follow-up, to patients from the observational cohort of the BILCAP study undergoing structured follow-up. Primary outcome was overall survival. RESULTS: A total of 315 patients were included n=91 pragmatic, n=224 structured follow-up). At median follow-up of 56.9 months, 189 (60%) patients were diagnosed with recurrence. After recurrence, more patients received palliative (chemo) therapy in the structured group (43% vs 75%, P<0.001). Median overall survival was lower in the pragmatic group (27.7 vs 39.1 months, P=0.003). Median overall survival of patients who actually received chemotherapy was comparable (27.2 vs 27.7 months, P=0.574). CONCLUSION: This study describes the results of two follow-up strategies. Although these groups are biased, it is noted that after pragmatic follow-up fewer patients received palliative chemotherapy but that those who actually received chemotherapy had similar overall survival compared to patients undergoing structured follow-up

Omineca Herald, May, 23, 1924

Background: LKB1 mutations are the underlying genetic abnormality causing Peutz-Jeghers syndrome (PJS) and are a potential target for everolimus. In this phase II study, the efficacy of everolimus on polyp and tumor growth in PJS patients was investigated. Methods: Adult patients with a proven LKB1 mutation and who were suitable for everolimus treatment were included in two different PJS cohorts: (a) patients with unresectable malignancies and (b) patients with high-risk polyps. Treatment in both groups was oral everolimus, 10 mg daily. Response rates were primary endpoints for both cohorts. Results: Between October 2011 and April 2016, only two patients were enrolled, one in each cohort. A 49-year-old patient with advanced pancreatic cancer in cohort 1 was progressive after 2 months. A 52-year-old male patient in cohort 2 experienced severe toxicity and refused treatment after 4 months, even though endoscopy suggested stabilization of polyps. Adverse

Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67

Background: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. Methods: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0–5 and Ki67 6–20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. Results: The study enrolled 241 patients (86%) with Ki67 0–5% and 39 patients (14%) with Ki67 6–20%. Recurrence was seen in 34 patients (14%) with Ki67 0–5% after a median period of 34 months and in 16 patients (41%) with Ki67 6–20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0–5% and respectively 55 and 26% for Ki67 6–20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. Conclusions: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed

The value of sorafenib trough levels in patients with advanced hepatocellular carcinoma - a substudy of the SORAMIC trial.

Background: Sorafenib for advanced hepatocellular carcinoma (HCC) is dose adjusted by toxicity. Preliminary studies have suggested an association between plasma concentrations of sorafenib and its main metabolite (M2) and clinical outcomes. This study aimed to validate these findings and establish target values for sorafenib trough concentrations.Methods: Patients with advanced HCC were prospectively recruited within a multicenter phase II study (SORAMIC). Patients with blood samples available at trough level were included for this pharmacokinetic (PK) substudy. Trough plasma concentrations of sorafenib and its main metabolite (M2) were associated with sorafenib-related toxicity and overall survival (OS).Results: Seventy-four patients were included with a median OS of 19.7 months (95% CI 16.1-23.3). Patients received sorafenib for a median of 51 weeks (IQR 27-62) and blood samples were drawn after a median of 25 weeks (IQR 10-42). Patients had a median trough concentration of 3217 ng/ml (IQR 2166-4526) and 360 ng/ml (IQR 190-593) with coefficients of variation of 65% and 146% for sorafenib and M2, respectively. Patients who experienced severe sorafenib-related toxicity received a lower average daily dose (551 vs 730 mg/day, p = .003), but showed no significant differences in sorafenib (3298 vs 2915 ng/ml, p = .442) or M2 trough levels (428 vs 283 ng/ml, p = .159). Trough levels of sorafenib or M2 showed no significant association with OS.Conclusions: In patients with advanced HCC treated with sorafenib, the administered dose, trough levels of sorafenib or M2, and clinical outcomes were poorly correlated. Toxicity-adjusted dosing remains the standard for sorafenib treatment

Are we SHARP enough? The importance of adequate patient selection in sorafenib treatment for hepatocellular carcinoma

Background: Upon FDA/EMEA registration for hepatocellular carcinoma (HCC), sorafenib received a broader therapeutic indication than the eligibility criteria of the landmark SHARP trial. This allowed treatment of SHARP non-eligible patients in daily clinical practice. Aim: To assess sorafenib efficacy and safety in SHARP eligible and non-eligible patients, and determine the validity of the current therapeutic indication as described by the FDA/EMEA. Patients and methods: Consecutive patients treated with sorafenib for advanced HCC at two Dutch tertiary referral centers between 2007 and 2016 were analyzed retrospectively. Primary outcome was overall survival (OS). Secondary outcomes were time to progression (TTP), response rate, adverse events and reasons for discontinuation. Outcomes were compared between SHARP eligible and non-eligible patients. Results: One hundred and ninety-three of 257 (75%) patients were SHARP eligible. SHARP eligible patient

Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs)

Nationwide treatment and outcomes of intrahepatic cholangiocarcinoma

Background: Most data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort. Methods: Data on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Results: In total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P &lt; 0.001). Discussion: Half of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers

National consensus on a new resectability classification for perihilar cholangiocarcinoma - A modified Delphi method

Background: Currently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study. Method: Using the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed. Results: The five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease. Conclusion: This DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies.</p