Development of a Decision-Aid Form (DAF) for the stratification of care in a French comprehensive cancer center, a tool to support identification of care goals.

BACKGROUND: For cancer patients, life-threatening complications may be difficult to anticipate, which can lead to complex medical decision-making processes. Since 2015, the Gustave Roussy Cancer Center has used a Decision-Aid Form (DAF), which contains an estimated gradation of care in cases where patients' conditions worsen. In this study, we assessed the acceptability of the DAF and the predictive value of the proposed stratification of care with regard to care delivered and patient's outcomes. METHODS: During a 5-month period, all patients who had been transferred from Site 1 to Site 2 of the hospital were prospectively included. RESULTS: A DAF was completed for 89.3% of the 206 patients included. Planned stratification of care was indicated in nearly all cases. The involvement of the palliative care team was indicated in only 29% of the DAF. The value of the WHO/ECOG Performance Status (PS) was limited. Finally, the field "information for patients and relatives" was infrequently completed. Although the possibility of transfer to the Intensive Care Unit was proposed for two-thirds of the patients, 76% of the 35 patients experiencing an acute event received only medical or palliative care. Overall, the level of therapeutic commitment suggested by the DAF was most often revised towards less aggressive care. CONCLUSIONS: The results of our study suggest that implementing an advanced stratification record is possible in a French cultural setting. To achieve complete cultural acceptance, our large integrated institutional program continues to play a key role in anticipating intent, tracing and sharing information with patients and their relatives.

A microsimulation model to assess the economic impact of immunotherapy in non-small cell lung cancer.

INTRODUCTION: Immunotherapy has become the standard of care in advanced non-small cell lung cancer (NSCLC). We aimed to quantify the economic impact, in France, of anti-PD-1 therapy for NSCLC. METHODS: We used patient-level data from the national ESCAP-2011-CPHG cohort study to estimate time to treatment failure and mean cost per patient for the four label indications approved by the European Medicines Agency (EMA) for NSCLC in May 2018. To compute the budget impact, we used a microsimulation model to estimate the target populations of anti-PD-1 therapy over a 3-year period, which were combined with the annual cost of treatment. RESULTS: Overall, 11 839 patients with NSCLC were estimated to be eligible for anti-PD-1 therapy 3 years after the introduction of anti-PD-1 therapies. The mean annual cost per patient in the control group ranged from €2671 (95% CI €2149-3194) to €6412 (95% CI €5920-6903) across the four indications. The mean annual cost of treatment for the four EMA-approved indications of anti-PD-1 therapy was estimated to be €48.7 million in the control group and at €421.8 million in the immunotherapy group. The overall budget impact in 2019 is expected to amount to €373.1 million. In the sensitivity analysis, flat doses and treatment effect had the greatest influence on the budget impact. CONCLUSION: Anti-PD-1 agents for NSCLC treatment are associated with a substantial economic burden.

High-dose cyclophosphamide for hard-to-treat patients with relapsed or refractory B-cell non-Hodgkin's lymphoma, a phase II result.

BACKGROUND: High-dose cyclophosphamide to treat solid refractory tumors demonstrated meaningful activity, while data to treat lymphoma remain scarce. This study aims to assess high-dose cyclophosphamide to treat relapsed or refractory lymphoma. METHODS: A phase II study included adult patients with relapsed or refractory B-cell non-Hodgkin's lymphoma, previously treated by ≥2 prior lines with no other available option of therapy. High-dose cyclophosphamide was given intravenously 3 g/m2 over two consecutive days and repeated once at 28 days in responding patients. Rituximab 375 mg/m2 intravenously was added in patients not refractory to anti-CD20 antibody. RESULTS: Forty-two patients with median age 65 [56-70] years were included. Patients had previously received a median of four lines of therapies. Tumor types were diffuse large B-cell lymphoma (n = 26; 62%), indolent B-cell non-Hodgkin lymphoma (n = 10; 24%), or mantle lymphoma (n = 6; 14%). Hematologic and non-hematologic grade 3-5 toxicities occurred in 42 (100%) and 18 (43%) of patients, respectively. The overall response rate was 45%. CONCLUSION: One to two cycles of high-dose cyclophosphamide in hard-to-treat patients with relapsed or refractory B-cell non-Hodgkin lymphoma demonstrated a favorable safety and efficacy profile. This regimen could serve as a bridge to modern cellular therapy with CAR-T cell.

Impact of hypnosis on patient experience after venous access port implantation.

INTRODUCTION: Hypnosis has been reported to decrease pain and anxiety in surgical context, but data studying its impact on patient experience using a validated scale are scarce. In the present study, we assessed the effect of an audio hypnosis session on patient satisfaction during venous access port implantation under local anaesthesia in adult cancer patients using the EVAN-LR Score. METHODS: After informed consent, patients were randomised to receive either hypnosis or standard care. The hypnosis group listened to a 26 minutes recorded audio hypnosis session through the ongoing implantation procedure. The primary outcome was the result of the EVAN-LR questionnaire, assessing perioperative experience in patients undergoing anaesthesia without loss of consciousness. This score describes a global index and 5 dimensions of experience: comfort, pain attention, information and waiting. It is scaled from 0 to 100 with 100 indicating the best possible level of satisfaction. Secondary outcomes included patient's anxiety, heart rate before and after procedure, procedure duration and several Visual Analogic Scale to match EVAN-LR dimensions. RESULTS: Overall, 148 patients were enrolled in the study. The global index of Evan-LR was significantly higher in the hypnosis session group (78 ± 14) compared to the standard care group (71 ± 17) (P = 0.006). No difference was reported in secondary outcomes. CONCLUSION: A recorded audio hypnosis session during subcutaneous venous port implantation under local anaesthesia in cancer patients significantly improved patient satisfaction.

A retrospective, matched paired analysis comparing bendamustine containing BeEAM versus BEAM conditioning regimen: results from a single center experience.

The combination of carmustine, etoposide, aracytin, and melphalan(BEAM) conditioning regimen in autologous stem-cell transplantation (ASCT) is widely used in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. It is also an option in patients with very-high risk aggressive NHL in first complete remission (CR). Recently, a phase Ib-II feasibility study using bendamustine replacing carmustine (BCNU) was reported. We report herein a safety and efficacy analysis of bendamustine-EAM (BeEAM) with a control BEAM counterpart paired cohort (1/2). One hundred and two patients were analyzed. Overall survival (OS) and progression-free survival (PFS) were not reached and seemed to be comparable between both groups. However, grade III or greater diarrhea was significantly higher in BeEAM patients (44 vs. 15%, p = .002). The median number of days with fever >38 °C was significantly higher in BeEAM group (5.5 vs. 2, p < .001). This case-control study suggests that BeEAM followed by ASCT using bendamustine at 100 mg/m2/d is effective but has a different toxicity profile than the BEAM regimen.

Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase-mutated intrahepatic cholangiocarcinomas.

Therapeutic resources are limited for advanced biliary tract cancers and prognosis remains poor. Somatic mutations in isocitrate dehydrogenase (IDH)1/2 gene are found in 5-36% of patients with intrahepatic cholangiocarcinoma (ICC). The mutant forms of IDH1/2 catalyse the non-reversible accumulation of 2-hydroxyglutarate (2HG). Increasing numbers of indirect or direct-targeted therapies are developed to IDH1/2 mutations and could be assisted by a routinely feasible, rapid and inexpensive serum 2HG measurement by liquid chromatography coupled to tandem mass spectrometry. By comparing eight patients with an IDH1/2-mutated ICC to nine patients with wild-type IDH1/2 ICC, we found significantly higher levels of 2HG in patients with IDH1/2 mutations versus the wild-type group (median, 10.9 vs. 0.8 µmol/L, p = 0.0037). D and L-2HG enantiomer levels significantly differed between the two groups with a higher level of D-2HG (p < 0.0001) in patients with IDH1/2 mutations. Accordingly, the D/L ratio was markedly higher in the patients with IDH1/2 mutations compared with the wild-type group (38.0 vs. 0.9 µmol/L, p < 0.0001). D-2HG measurement ensured 100% sensitivity and specificity at a cut-off of 0.6 µmol/L. D-2HG levels were correlated with tumour burden and tumour response to treatment with IDH-targeted therapies or indirect therapies. D-2HG serum level measurement by liquid chromatography coupled to tandem mass spectrometry is a sensitive, specific, precise (a coefficient of variation <10% and an accuracy >95%), fast (9 min run per sample) and inexpensive surrogate marker of IDH1/2 somatic mutation in ICC. Systematic measurement in patients with ICC may facilitate access to, and monitoring of, IDH-driven therapies.

Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial.

BACKGROUND: Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC. OBJECTIVE: To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance. RESULTS AND LIMITATIONS: Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p=0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p=0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3-4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups. CONCLUSIONS: Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients. PATIENT SUMMARY: Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.