A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer.

BACKGROUND: FOLFIRINOX is a pillar first-line regimen in the treatment of pancreatic cancer. Historically, biliary tract cancer (BTC) and pancreatic cancer have been treated similarly with gemcitabine alone or combined with a platinum compound. With growing evidence supporting the role of fluoropyrimidines in the treatment of BTC, we aimed at assessing the outcomes of patients (pts) with BTC on frontline FOLFIRINOX. METHODS: We retrospectively analyzed data of all our consecutive patients with locally advanced (LA) or metastatic (M) BTC who were registered to receive FOLFIRINOX as a first-line therapy between 12/2013 and 11/2017 at Paul Brousse university hospital. The main endpoints were Overall Survival (OS), Time-to-Progression (TTP), best Objective Response Rate (ORR), Disease Control rate (DCR), secondary macroscopically-complete resection (res) and incidence of severe (grade 3-4) toxicity (tox). RESULTS: There were 17 male (40%) and 25 female (60%) pts. aged 36 to 84 years (median: 67). They had PS of 0 (55%) or 1 (45%), and intrahepatic cholangiocarcinoma (CCA) (21 pts., 50%), gallbladder carcinoma (8 pts., 19%), perihilar CCA (7 pts., 17%), distal CCA (4 pts., 10%) and ampulloma (2 pts., 5%). BTC was LA or M in 10 (24%) and 32 pts. (76%) respectively. Biliary stent was placed in 14 pts. (33%). A median of 10 courses was given with median treatment duration of 6 months. There were no untoward toxicity issues, with no febrile neutropenia, emergency admission for toxicity or toxic death. We observed 12 partial responses (29%) and 19 disease stabilisations (45%). Six patients (14%) underwent secondary R0-R1 resection. Median TTP was 8 months [95%CL, 6-10] and median OS was 15 months [13-17]. Patients undergoing secondary resection displayed a 3-y disease-free rate of 83%. CONCLUSIONS: First-line FOLFIRINOX offers promising results in patients with LA and M-BTC. It deserves prospective evaluation to further improve outcomes for advanced BTC.

Clinical Relevance of the First Domomedicine Platform Securing Multidrug Chronotherapy Delivery in Metastatic Cancer Patients at Home: The inCASA European Project.

BACKGROUND: Telehealth solutions can improve the safety of ambulatory chemotherapy, contributing to the maintenance of patients at their home, hence improving their well-being, all the while reducing health care costs. There is, however, need for a practicable multilevel monitoring solution, encompassing relevant outputs involved in the pathophysiology of chemotherapy-induced toxicity. Domomedicine embraces the delivery of complex care and medical procedures at the patient's home based on modern technologies, and thus it offers an integrated approach for increasing the safety of cancer patients on chemotherapy. OBJECTIVE: The objective was to evaluate patient compliance and clinical relevance of a novel integrated multiparametric telemonitoring domomedicine platform in cancer patients receiving multidrug chemotherapy at home. METHODS: Self-measured body weight, self-rated symptoms using the 19-item MD Anderson Symptom Inventory (MDASI), and circadian rest-activity rhythm recording with a wrist accelerometer (actigraph) were transmitted daily by patients to a server via the Internet, using a dedicated platform installed at home. Daily body weight changes, individual MDASI scores, and relative percentage of activity in-bed versus out-of-bed (I

Transanal small bowel evisceration: A case report and literature review.

INTRODUCTION: Transanal small bowel evisceration remains a rarely recorded emergent situation in the scientific literature. This article describes the rather seldom complication of a non-treated long standing rectal prolapse presenting in the form of transanal prolapse of the small bowel due to rectal perforation. PRESENTATION OF CASE: We present the case of an 84 year old female, who presented to our emergency department with transanal evisceration of the small bowel. DISCUSSION: This rare case presentation led us to perform an accompanying review of the literature, using Pubmed® searching for the words "transanal evisceration", "rectal prolapse", and "rectal perforation". We discuss the outcomes of our literature review, possible pathogenesis and the available treatment options. CONCLUSION: Although transanal evisceration of small bowel presents a rare emergency, having the knowledge of this condition would help early recognition of this incidence and hopefully lead to early treatment, which would avoid drastic consequences as a result of small bowel strangulation.

The day after: correlates of patient-reported outcomes with actigraphy-assessed sleep in cancer patients at home (inCASA project).

Subjective sleep assessment in cancer patients poorly correlates with actigraphy parameters that usually encompass multiple nights. We aimed to determine the objective actigraphy measures that best correlated with subjective sleep ratings on a night-by-night basis in cancer patients. Thirty-one cancer patients daily self-rated sleep disturbances using the single dedicated item of the MD Anderson Symptom Inventory (0-10 scale) with 18 other items, and continuously wore a wrist actigraph for 30 days. Objective sleep parameters were computed from the actigraphy nighttime series, and correlated with subjective sleep disturbances reported on the following day, using repeated measures correlations. Multilevel Poisson regression analysis was performed to identify the objective and subjective parameters that affected subjective sleep rating. Poor subjective sleep score was correlated with poor sleep efficiency (rrm = -0.13, p = 0.002) and large number of wake episodes (rrm = 0.12, p = 0.005) on the rated night. Multilevel analysis demonstrated that the expected sleep disturbance score was affected by the joint contribution of the wake episodes (exp(ß) = 1.01, 95% confidence interval = 1.00 to 1.02, p = 0.016), fatigue (exp(ß) = 1.35, 95% confidence interval = 1.15 to 1.55, p < 0.001) and drowsiness (exp(ß) = 1.70, 95% confidence interval = 1.19 to 2.62, p = 0.018), self-rated the following evening, and sleep disturbance experienced one night before (exp(ß) = 1.77, 95% confidence interval = 1.41 to 2.22, p < 0.001). The night-by-night approach within a multidimensional home tele-monitoring framework mainly identified the objective number of wake episodes computed from actigraphy records as the main determinant of the severity of sleep complaint in cancer patients on chemotherapy. This quantitative information remotely obtained in real time from cancer patients provides a novel framework for streamlining and evaluating interventions toward sleep improvement in cancer patients.

Patient-tailored FOLFIRINOX as first line treatment of patients with advanced pancreatic adenocarcinoma.

FOLFIRINOX is one of the most effective reference regimens in the 1st line treatment of locally advanced (LA) and metastatic pancreatic cancer (mPC), despite its high toxicity. We evaluated our real-life experience with "patient-tailored intent to treat FOLFIRINOX" in patients with LA or mPC compared to other reports along with the pivotal phase III trial.We analyzed data from all consecutive patients with pancreatic ductal adenocarcinoma treated with dose-modified FOLFIRINOX in 2016 at Paul Brousse University Hospital. Irinotecan was administered whenever initial serum bilirubin was <1.5 × upper limit of normal. Oxaliplatin was stopped for severe sensory neuropathy. Initial dose reductions were made according to patient profile (eg, age, comorbidities) and later due to toxicity. The treatment was continued until surgery or disease progression. Endpoints were time to progression (TTP), overall survival (OS), objective response rate (ORR), and secondary complete resection (R0R1).Thirty-seven patients with unresectable LA or mPC received patient-tailored FOLFIRINOX as 1st line chemotherapy. There were 22 male (59%) and 15 female patients (41%) aged 44 to 81 years with LA (18 patients, 49%) and mPC (19 patients, 51%). They had World Health Organization-performance status of 0 (59%) or 1 (41%). A total of 384 cycles were administered. Median dose intensities (mg/m/w) were 28.9 for oxaliplatin, 56.8 for irinotecan, and 886.2 for 5-fluorouracil. Thirty-four patients were assessed for response; ORR and disease control rates were 47% and 85%, respectively. R0R1 rate was 30%. Median TTP and OS were 9.6 and 14.6 months. LA disease was associated with significantly longer TTP and OS (P < .001).FOLFIRINOX with patient-tailored dose adaptations seems to offer better results in patients with advanced PC. This approach in the neoadjuvant setting results in a macroscopic R0R1 in 61% of patients with initially unresectable disease. It deserves prospective evaluation to further improve outcomes in the management of advanced PC.

Home-Based e-Health Platform for Multidimensional Telemonitoring of Symptoms, Body Weight, Sleep, and Circadian Activity: Relevance for Chronomodulated Administration of Irinotecan, Fluorouracil-Leucovorin, and Oxaliplatin at Home-Results From a Pilot Study.

PURPOSE: To assess the impact of chronomodulated irinotecan fluorouracil-leucovorin and oxaliplatin (chronoIFLO4) delivered at home on the daily life of patients with cancer in real time using a home-based e-Health multifunction and multiuser platform. This involved multidimensional telemonitoring of circadian rest-activity rhythm (CircAct), sleep, patient-reported outcome measures, and body weight changes (BWCs). PATIENTS AND METHODS: Patients received chronoIFLO4 fortnightly at home. Patients completed the 19-item MD Anderson Symptom Inventory on an interactive electronic screen, weighed themselves on a dedicated scale, and continuously wore a wrist accelerometer for CircAct and sleep monitoring. Daily data were securely teletransmitted to a specific server accessible by the hospital team. The clinically relevant CircAct parameter dichotomy index I < O and sleep efficiency (SE) were calculated. The dynamic patterns over time of patient-reported outcome measures, BWC, I < O, and SE informed the oncology team on tolerance in real time. RESULTS: The platform was installed in the home of 11 patients (48 to 72 years of age; 45% men; 27% with performance status = 0), who were instructed on its use on site. They received 26 cycles and provided 5,891 data points of 8,736 expected (67.4%). The most severe MD Anderson Symptom Inventory scores were: interference with work (mean: 5.1 of 10) or general activity (4.9), fatigue (4.9), distress (4.2), and appetite loss (3.6). Mean BWC was -0.9%, and mean SE remained > 82%. CircAct disruption (I < O ≤ 97.5%) was observed in four (15%) cycles before chronoIFLO4 start and in five (19%) cycles at day 14. CONCLUSION: The patient-centered multidimensional telemonitoring solution implemented here was well accepted by patients receiving multidrug chemotherapy at home. Moreover, it demonstrated that chronoIFLO4 was a safe therapeutic option. Such integrated technology allows the design of innovative management approaches, ultimately improving patients' experience with chemotherapy, wellbeing, and outcomes.

Circadian rest-activity rhythm as an objective biomarker of patient-reported outcomes in patients with advanced cancer.

BACKGROUND: Psychosocial symptoms often cluster together, are refractory to treatment, and impair health-related quality of life (HR-QoL) in cancer patients. The contribution of circadian rhythm alterations to systemic symptoms has been overlooked in cancer, despite a causal link shown under jet lag and shift work conditions. We investigated whether the circadian rest-activity rhythm provides a reliable and objective estimate of the most frequent patient-reported outcome measures (PROMs). METHODS: Two datasets were used, each involving concomitant 3-day time series of wrist actigraphy and HR-QoL questionnaires: EORTC QLQ-C30 was completed once by 237 patients with metastatic colorectal cancer; MD Anderson Symptom Inventory (MDASI) was completed daily by 31 patients with advanced cancer on continuous actigraphy monitoring, providing 1015 paired data points. Circadian function was assessed using the clinically validated dichotomy index I < O. Nonparametric tests compared PROMs and I < O. Effect sizes were computed. Sensitivity subgroup and temporal dynamics analyses were also performed. RESULTS: I < O values were significantly lower with increasing symptom severity and worsening HR-QoL domains. Fatigue and anorexia were worse in patients with circadian disruption. The differences were both statistically and clinically significant (P < 0.001; d ≥ 0.33). Physical and social functioning, and global quality/enjoyment of life were significantly better in patients with robust circadian rhythm (P < 0.001; d ≥ 0.26). Sensitivity analyses validated these findings. CONCLUSION: Objectively determined circadian disruption was consistently and robustly associated with clinically meaningfully severe fatigue, anorexia, and interference with physical and social functioning. This supports an important role of the circadian system in the determination of cancer patients' HR-QoL and symptoms that deserves therapeutic exploitation.

Tailgut cyst: A case report and literature review.

INTRODUCTION: Tailgut cysts are rare diseases but can be challenging to manage. PRESENTATION OF CASE: This is a case report of a tailgut cyst, in a 42 year old female. The cyst was incidentally detected on imaging, and treated with Kraske surgical approach. DISCUSSION: Hereby, we review the relevant information present in the medical literature about the incidence, methods of diagnosis, treatment options and management plans. CONCLUSION: Surgical management should be tailored individually for each patient, based on the advantages and disadvantages of each surgical approach.

Elevated heparin-induced antibodies are more common in diabetic patients with vascular disease.

Background. Hypercoagulable disorders can lead to deep vein thrombosis (DVT), arterial thrombosis or embolization, and early or recurrent bypass graft failure. The purpose of this study was to identify whether diabetes increased the likelihood of heparin-induced platelet factor 4 antibodies in at risk vascular patients. Methods. We reviewed clinical data on 300 consecutive patients. A hypercoagulable workup was performed if patients presented with (1) early bypass/graft thrombosis (<30 days), (2) multiple bypass/graft thrombosis, and (3) a history of DVT, pulmonary embolus (PE), or native vessel thrombosis. Relevant clinical variables were analyzed and compared between patients with diabetes (DM) and without diabetes (nDM). Results. 85 patients (47 women; age 53 ± 16 years, range 16-82 years) had one of the defined conditions and underwent a hypercoagulable evaluation. Screening was done in 4.7% of patients with early bypass graft thrombosis, 60% of patients were screened because of multiple bypass or graft thrombosis, and 35.3% had a previous history of DVT, PE, or native vessel thrombosis. Of the 43 patients with DM and 42 nDM evaluated, 59 patients (69%) had an abnormal hypercoagulable profile. An elevated heparin antibody level was present in 30% of DM and 12% of nDM patients (chi-squared test P < 0.04). Additionally, DM was associated with a higher likelihood of arterial complications while nDM was associated with a higher rate of venous adverse events (chi-squared test P < 0.003). Conclusions. Diabetes is associated with a higher likelihood of developing heparin-induced antibodies and an increased combined incidence of arterial complications that include early or multiple bypass/graft thrombosis. This finding may influence the choice of anticoagulation in diabetic patients at risk with vascular disease.

Acute renal failure related to oxaliplatin-induced intravascular hemolysis.

Oxaliplatin is an effective chemotherapeutic agent frequently used in the treatment of colorectal carcinoma. Rare cases of renal failure and hemolytic reactions have been reported as separate side effects of oxaliplatin. Here we present a clinical picture of immune-related intravascular hemolysis and acute tubular necrosis in a patient receiving this drug. This case suggests a mechanistic explanation of renal failure in patients treated with oxaliplatin.