Acute Pancreatitis Following Peptide Receptor Radionuclide Therapy: An Unusual Adverse Event

A 54-year-old man with grade 2 rectal neuroendocrine tumor and hepatic, pancreatic, and bone metastases was treated with 177Lu-DOTATATE as second-line therapy, after failure of somatostatin analogues. Two weeks after the first injection, he presented at the emergency department with acute pancreatitis. We hypothesized that this unusual adverse event, never been reported so far, was the result of acute tumor irradiation after PRRT, leading to peritumoral inflammation and edema with obstruction of an accessory pancreatic duct.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Predictive factors for cancer-associated thrombosis in a large retrospective single-center study

Background: The relationship between cancer and thrombosis has been studied for years, but reliable guidelines for thromboprophylaxis in that situation are still unclear. Methods: We retrospectively reviewed the files of 3159 consecutive patients with newly diagnosed solid tumors at Jules Bordet Institute from January 2008 to December 2011. Among them, 99 developed a symptomatic thromboembolic episode and were matched with 2 controls (nested case control). The aim was to identify risk factors of thromboembolic events and to validate in our setting the Khorana score. Results: In the cohort study, nodal status ≥ 2, presence of metastases, and primary tumor site were found to be the most significant predictive factors of a thromboembolic event (n = 99; 3.1%) in the multivariate analysis. In the nested study (n = 265), hemoglobin 0.96 mg/dL, chronic inflammatory disease, and personal or familial history of thromboembolic events were found to be the most significant predictive factors of a thromboembolic event in the multivariate analysis. In our population, the sensitivity, specificity, positive predictive value, and negative predictive value of the Khorana score were respectively 29%, 93%, 15%, and 96%. Conclusion: We confirm the value of the risk factors identified in the literature with the additional presence of nodal involvement, elevated CRP, and creatinine levels, which may be helpful for patient risk stratification and should be considered in future clinical trials. Our results also suggest that the Khorana score might help to identify patients who can safely be spared of thromboprophylaxis.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Is positron emission tomography (PET) with FDG an early predictor of the RECIST morphological response to chemotherapy in metastatic colorectal cancer patients (mCRC)?

Background: Reliable early assessment of response would help identify active treatments and avoid unnecessary side effects. Our hypothesis was that FDG-PET metabolic changes 2 weeks after the first dose of chemotherapy predict standard morphological response. Methods: 45 mCRC patients undergoing 1st or 2nd-line chemotherapy are planned to be included in a prospective trial comparing early metabolic changes, as measured by serial FDG-PET, with the standard RECIST- based response assessment using multi-slice CT. A signed informed consent was obtained in all cases. For the lesion-by-lesion analysis, according to the EORTC recommendations, a metabolic response was defined as a ≥ 15% decrease of the standardized FDG uptake (SUVmax) on day 14. A patient was classified as having overall metabolic responsive disease if the majority or all lesions observed on the baseline PET showed a metabolic response, without any progressive lesion ( ≥25% increase). Results: At interim analysis, 28 patients (median age 65.9 yrs) were available for comparative metabolic and morphological analysis of 88 lesions. Mean number of lesions per patient was 3 (range 1–8). Patients received FOLFOX (18), FOLFIRI (9), and capecitabine (1) as first- (19) or second-line (9) treatments. Metabolic assessment showed 49 (56%) responding and 39 (44%) nonresponding lesions. The morphological response rate in metabolically non-responding lesions (5/39; 13%) was lower than in responding lesions (22/49; 45%) (p = 0.001; Fisher's exact test). A mixed metabolic response, combining responding and non-responding lesions within the same patient, was seen in 21/28 (75%) pts. A RECIST response was observed in 6/14 (43%) PET responding and in 0/14 (0%) PET nonresponding patients (p = 0.02; Fisher's Exact test). Updated results of this ongoing trial will be presented. Conclusions: Serial FDG PET seems able to identify non-responding mCRC disease after one course of chemotherapy. No significant financial relationships to disclose

Prognostic value of a three-scale grading system based on combining molecular imaging with 68Ga-DOTATATE and 18F-FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias

info:eu-repo/semantics/publishe

Correlating tumor metabolic progression index measured by serial FDG PET-CT, apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and blood genomics to patient's outcome in advanced colorectal cancer: The CORIOLAN study

Background: Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome.Methods/Design: CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC.Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps.Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome.Discussion: Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging of patients with chemorefractory mCRC during a period of time without treatment. Results will be correlated to other assessment tools like DW-MRI, CTCs and circulating DNA, with the aim to provide usable tools in daily practice and in clinical studies in the future.Clinical trials.gov number: NCT01591590. © 2014 Deleporte et al. licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept.

BACKGROUND: The aim of this study is to investigate the role of Octreotide LAR in secondary prevention in patients with chemotherapy-induced diarrhea. METHODS: In this study, patients experiencing CID ≥ grade 2 received 30 mg long-acting octreotide as a monthly injection and the next chemotherapy dose was administrated with a 25% dose decrease. If no CID ≥ grade 2 occurred, subsequent chemotherapy doses were increased to the initial 100% values. The primary endpoint of the study was the diarrhea control rate (< grade 2) for patients receiving the optimal dose of chemotherapy for a minimum of 2 cycles. RESULTS: Twenty-nine patients were included. Ten patients experienced no improvement or ended the study very early after the first injection of octreotide LAR. Nineteen patients had a reduction in the grade of diarrhea after the first administration of Octreotide LAR and a reduced chemotherapy dose. Seven of them (24%) did not reach the end of the study because of disease progression (6) or lost in follow-up (1). Ultimately 12 patients (41%) continued the study till the end. In ten of these twelve patients, there was a significant and persisting reduction of diarrhea while receiving full dose chemotherapy. CONCLUSION: This study suggests that monthly injections with long-acting octreotide might be used as a secondary prevention of chemotherapy-induced diarrhea. Its usefulness and optimal dosage in secondary prevention in combination with antidiarrheal agents needs further research

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept.

BACKGROUND: The aim of this study is to investigate the role of Octreotide LAR in secondary prevention in patients with chemotherapy-induced diarrhea. METHODS: In this study, patients experiencing CID ≥ grade 2 received 30 mg long-acting octreotide as a monthly injection and the next chemotherapy dose was administrated with a 25% dose decrease. If no CID ≥ grade 2 occurred, subsequent chemotherapy doses were increased to the initial 100% values. The primary endpoint of the study was the diarrhea control rate (< grade 2) for patients receiving the optimal dose of chemotherapy for a minimum of 2 cycles. RESULTS: Twenty-nine patients were included. Ten patients experienced no improvement or ended the study very early after the first injection of octreotide LAR. Nineteen patients had a reduction in the grade of diarrhea after the first administration of Octreotide LAR and a reduced chemotherapy dose. Seven of them (24%) did not reach the end of the study because of disease progression (6) or lost in follow-up (1). Ultimately 12 patients (41%) continued the study till the end. In ten of these twelve patients, there was a significant and persisting reduction of diarrhea while receiving full dose chemotherapy. CONCLUSION: This study suggests that monthly injections with long-acting octreotide might be used as a secondary prevention of chemotherapy-induced diarrhea. Its usefulness and optimal dosage in secondary prevention in combination with antidiarrheal agents needs further research

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea

Introduction : Chemotherapy-induced diarrhea (CID) is one of the most disturbing side effects of chemotherapy with respect to the patient’s quality of life, often dose-limiting if not calling into question the entire therapeutic strategy. CID prevention could enhance treatment safety and outcome by enabling the administration of optimal therapeutic doses. Diarrhea prevention is a major challenge for future oncological therapies, as CID is a frequent side effect of modern biological agents. In this multicentric, Belgian, prospective non-randomized trial, we tested the secondary prevention of CID with long-acting octreotide (LAO) in patients receiving cytotoxic chemotherapy associated with a high risk of digestive toxicity. Methods : In the study’s observational phase, all patients treated with a high-risk chemotherapy regimen were prospectively screened after having provided written consent. Patients experiencing a CID = 2 were proposed to enter the interventional phase, after having signed a second informed consent. They received a monthly Sandostatin LAR30 IM injection and the next chemotherapy course was administered with a 25% dose decrease. If no grade = 2 CID occurred, subsequent chemotherapy doses were increased to the initial 100% values. The main endpoint of the study was the diarrhea control rate for patients participating in the interventional phase of the study and receiving the optimal dose of chemotherapy for a minimum of 2 cycles. The statistical plan used a 2-step Simon design, with a first step after successful secondary CID prevention in 19 out of 25 patients. LAO would be considered as efficient in secondary prevention of CID if no diarrhea > grade 1 had been observed in at least 62 out of 79 patients treated with full-dose chemotherapy. Results : From March 2007 to March 2009, a total of 57 patients were included in the trial. The study was terminated before reaching its target size population because of poor accrual. 29 patients did not develop any CID and participated only in the observational phase. Of the 28 patients included in the interventional part after the first onset of a = grade 2 CID, 5 patients (17.8%, 95% CI = 6.1% - 36.9%) experienced no improvement after a 25% decrease in chemotherapy dose. 9 patients (32.1%, 95% CI = 15.9% - 52.4%) did not continue for the following reasons : rapid tumor progression (7), local reaction after LAO injection (1) and refusal (1). The screen failure rate is thus 14/28 (50%, 95% CI = 30.6% - 69.4%). Of the 14 patients whose CID was resolved after chemotherapy dose reduction, only 2 experienced a = grade 2 CID recurrence after receiving full dose chemotherapy. The remaining 12 patients were treated at the optimal chemotherapy dose without significant digestive side effects (85.7%, 95% CI = 57.2% - 98.2%). The overall success rate of the tested strategy is 12/28 (42.8%, 95% CI = 24.5% - 62.8%). Conclusions : While this trial did not recruit enough patients to answer the study question, available data suggest that LOA is very effective in allowing the return to optimal doses of chemotherapy in patients whose moderate to severe CID was improved after an initial chemotherapy dose reduction. Moreover, the high rate of screen failures emphasizes the need for more aggressive management of acute CID in addition to secondary prevention