Efficacy of second-line chemotherapy or immune checkpoint inhibitors for patients with a prolonged objective response (≥ 6 months) after first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma: a retrospective study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose. METHODS: Retrospective analysis (six French centers, 2008-2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. PRIMARY ENDPOINT: progression-free survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy. RESULTS: R/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line. Response after first-line: complete response (CR; n = 16, 11%); partial response (PR; n = 77, 53%); stable disease (n = 22, 15%). Second-line therapy: PBC (n = 95, 66%); platinum-free regimen (PFR) (n = 25, 17%); ICI (n = 24, 17%). Median [95% confidence interval] PFS (months): PBC 5.0 [3.8-6.2]; PFR 4.0 [1-7.0]; ICI 2.0 [0.4-3.6] (p = 0.16). For PBC, PFR, and ICI, respectively: OS1 30, 23, and 29 months (p = 1.02); OS2 14, 10, and 16 months (p = 0.25); PR, 26%, 16%, and 21% patients; CR, 0%, 8%, and 4% patients. For subsequent lines, ICIs were administered for PBC (n = 11, 12%) and PFR (n = 2, 8%). No predictive factor for efficacy (PFS, OS) was identified. CONCLUSIONS: Our retrospective study suggests similar efficacy regarding OS2 for second-line chemotherapy or ICI in R/M-HNSCC patients with progression ≥ 6 months after the last first-line platinum dose.

"Fortunately I felt pain, or I would have thought I was on my way out": experiencing pain and negotiating analgesic treatment in the context of cancer.

OBJECTIVES: To explore cancer patients' experience of pain and coping strategies as well as beliefs and representations associated with pain, pain management and treatments. METHOD AND PARTICIPANTS: A qualitative study based on semi-structured interviews was conducted among 16 patients with cancer. The inductive research strategy adopted derived from the Grounded Theory approach and the data transcribed verbatim were gradually analyzed involving researcher triangulation. FINDINGS: The experience of pain and the coping strategies developed by patients to deal with it are shaped by the experience and representations of cancer associated with death and suffering. Pain acts both as an indication to the patients that they are still alive and as an indicator of the progression of the disease. Cancer also models patients' relationships to analgesic treatments and health care providers, since pain is an area in which patients can take back control of what is happening to them. Patients' expression of reluctance to accept analgesic treatments is also influenced by the significance of opioid treatments in this context, which are perceived as an indication that the end of life is close. CONCLUSIONS: The contextualization of pain through the particularities of cancer is critical in order to understand cancer patients' experience of pain. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Not only patients' knowledge but also the meaning-making of pain should be incorporated in interventions targeting pain management.

Intensive end-of-life care in acute leukemia from a French national hospital database study (2017-2018).

BACKGROUND: A better understanding of how the care of acute leukemia patients is managed in the last days of life would help clinicians and health policy makers improve the quality of end-of-life care. This study aimed: (i) to describe the intensity of end-of-life care among patients with acute leukemia who died in the hospital (2017-2018) and (ii) to identify the factors associated with the intensity of end-of-life care. METHODS: This was a retrospective cohort study of decedents based on data from the French national hospital database. The population included patients with acute leukemia who died during a hospital stay between 2017 and 2018, in a palliative care situation (code palliative care Z515 and-or being in a inpatient palliative care support bed during the 3 months preceding death). Intensity end-of-life care was assessed using two endpoints: High intensive end-of-life (HI-EOL: intensive care unit admission, emergency department admission, acute care hospitalization, intravenous chemotherapy) care and most invasive end-of-life (MI-EOL: orotracheal intubation, mechanical ventilation, artificial feeding, cardiopulmonary resuscitation, gastrostomy, or hemodialysis) care. RESULTS: A total of 3658 patients were included. In the last 30 days of life, 63 and 13% of the patients received HI-EOL care and MI-EOL care, respectively. Being younger, having comorbidities, being care managed in a specialized hospital, and a lower time in a palliative care structure were the main factors associated with HI-EOL. CONCLUSIONS: A large majority of French young adults and adults with acute leukemia who died at the hospital experienced high intensity end-of-life care. Identification of factors associated with high-intensity end-of-life care, such as the access to palliative care and specialized cancer center care management, may help to improve end-of-life care quality.

The Prognostic Role of ß-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only: A Meta-analysis of Individual Patient Data.

OBJECTIVE: This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients. SUMMARY OF BACKGROUND DATA: The majority of sporadic DTF tumors harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types. METHODS: A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used. RESULTS: Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded a P-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48-1.42), 0.37 (95% CI 0.12-1.14), and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence. CONCLUSIONS: Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.

Palliative and high-intensity end-of-life care in schizophrenia patients with lung cancer: results from a French national population-based study.

Schizophrenia is marked by inequities in cancer treatment and associated with high smoking rates. Lung cancer patients with schizophrenia may thus be at risk of receiving poorer end-of-life care compared to those without mental disorder. The objective was to compare end-of-life care delivered to patients with schizophrenia and lung cancer with patients without severe mental disorder. This population-based cohort study included all patients aged 15 and older who died from their terminal lung cancer in hospital in France (2014-2016). Schizophrenia patients and controls without severe mental disorder were selected and indicators of palliative care and high-intensity end-of-life care were compared. Multivariable generalized log-linear models were performed, adjusted for sex, age, year of death, social deprivation, time between cancer diagnosis and death, metastases, comorbidity, smoking addiction and hospital category. The analysis included 633 schizophrenia patients and 66,469 controls. The schizophrenia patients died 6 years earlier, had almost twice more frequently smoking addiction (38.1%), had more frequently chronic pulmonary disease (32.5%) and a shorter duration from cancer diagnosis to death. In multivariate analysis, they were found to have more and earlier palliative care (adjusted Odds Ratio 1.27 [1.03;1.56]; p = 0.04), and less high-intensity end-of-life care (e.g., chemotherapy 0.53 [0.41;0.70]; p < 0.0001; surgery 0.73 [0.59;0.90]; p < 0.01) than controls. Although the use and/or continuation of high-intensity end-of-life care is less important in schizophrenia patients with lung cancer, some findings suggest a loss of chance. Future studies should explore the expectations of patients with schizophrenia and lung cancer to define the optimal end-of-life care.

High Serum Vitamin B12 Levels Associated with C-Reactive Protein in Older Patients with Cancer.

BACKGROUND: A Comprehensive Geriatric Assessment (CGA) has been proposed to assess prognosis and to adapt oncological care in older patients with cancer. However, few biological markers are incorporated in the CGA. METHODS: This comparative study on older patients with cancer was realized before final therapeutic decision and during a CGA that included biological markers. Our objective study was to know if the serum vitamin B12-C-reactive protein index (BCI) can help to estimate early death and unplanned hospitalization. Associations between BCI and unplanned hospitalization or mortality were analyzed using ordered multivariate logistic regression. FINDINGS: We included 621 older cancer adults in outpatient care with a median age of 81 years (range, 70-98 years) from September 2015 to May 2018. In this study, 5.6% of patients died within 3 months, 8.8% had unplanned hospitalization within 1 month, and 11.4% had unplanned hospitalization within 3 months. Hypercobalaminemia was present in 83 patients (13.4%), and 34 patients (5.5%) had BCI >40,000. According to the multivariate analysis, BCI was a prognostic factor of mortality within 3 months and unplanned hospitalizations at 1 and 3 months. Impaired activities of daily living (ADL) and palliative care were also risk factors for mortality within 3 months. Impaired instrumental ADL, low albumin level, and palliative care were risk factors for unplanned hospitalization at 1 month. INTERPRETATION: BCI could be routinely added to the CGA process, as part of a pretreatment workup, in order to assess more precisely the frailties and to adapt oncological care in older patients treated for cancer. IMPLICATIONS FOR PRACTICE: Aging comes with an increase of frailties and comorbidities. To identify frailties in older patients with cancer, this study used a Comprehensive Geriatric Assessment, which allowed for the adaptation of each treatment plan in accordance with the individual needs of the patients. However, biological characteristics were not included in this assessment. This study showed that hypercobalaminemia and vitamin B12 -C-reactive protein index may be potential markers for cancer with poor prognosis, particularly in the older population. These biological markers can be used in geriatric oncology and general medicine.

Impact on Health-Related Quality of Life of Parenteral Nutrition for Patients with Advanced Cancer Cachexia: Results from a Randomized Controlled Trial.

BACKGROUND: Malnutrition worsens health-related quality of life (HRQoL) and the prognosis of patients with advanced cancer. This study aimed to assess the clinical benefits of parenteral nutrition (PN) over oral feeding (OF) for patients with advanced cancer cachexia and without intestinal impairment. MATERIAL AND METHODS: In this prospective multicentric randomized controlled study, patients with advanced cancer and malnutrition were randomly assigned to optimized nutritional care with or without supplemental PN. Zelen's method was used for randomization to facilitate inclusions. Nutritional and performance status and HRQoL using the European Organization for Research and Treatment of Cancer QLQ-C15-PAL questionnaire were evaluated at baseline and monthly until death. Primary endpoint was HRQoL deterioration-free survival (DFS) defined as a definitive deterioration of ≥10 points compared with baseline, or death. RESULTS: Among the 148 randomized patients, 48 patients were in the experimental arm with PN, 63 patients were in the control arm with OF only, and 37 patients were not included because of early withdrawal or refused consent. In an intent to treat analysis, there was no difference in HRQoL DFS between the PN arm or OF arm for the three targeted dimensions: global health (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.88-1.94; p = .18), physical functioning (HR, 1.58; 95% CI, 1.06-2.35; p = .024), and fatigue (HR, 1.19; 95% CI, 0.80-1.77; p = .40); there was a negative trend for overall survival among patients in the PN arm. In as treated analysis, serious adverse events (mainly infectious) were more frequent in the PN arm than in the OF arm (p = .01). CONCLUSION: PN improved neither HRQoL nor survival and induced more serious adverse events than OF among patients with advanced cancer and malnutrition. Clinical trial identification number. NCT02151214 IMPLICATIONS FOR PRACTICE: This clinical trial showed that parenteral nutrition improved neither quality of life nor survival and generated more serious adverse events than oral feeding only among patients with advanced cancer cachexia and no intestinal impairment. Parenteral nutrition should not be prescribed for patients with advanced cancer, cachexia, and no intestinal failure when life expectancy is shorter than 3 months. Further studies are needed to assess the useful period with a potential benefit of artificial nutrition for patients with advanced cancer.

A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation.

Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.

Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study.

BACKGROUND: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated. PATIENTS AND METHODS: We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates. RESULTS: Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p < 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins (> 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. > 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS. CONCLUSIONS: This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.

Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study.

BACKGROUND: Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). PATIENTS AND METHODS: A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. RESULTS: 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31-80 months]. Median OS was 11.5 months (95% CI 7.5-18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27-6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14-0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049). CONCLUSIONS: The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.

End-of-Life Care Among Patients With Bipolar Disorder and Cancer: A Nationwide Cohort Study.

OBJECTIVE: This study aimed to describe end-of-life (EOL) care in individuals with bipolar disorder (BD) who died of cancer compared with mentally healthy individuals. METHODS: This was a nationwide cohort study of all adult individuals who died of cancer in hospitals in France between 2013 and 2016. Outcomes were compared between individuals with BD and mentally healthy individuals in the last month of life including palliative care and high-intensity EOL care (chemotherapy, artificial nutrition, and other interventions). A subanalysis explored differences between patients with BD and patients with schizophrenia. RESULTS: The study included 2015 individuals with BD and 222,477 mentally healthy controls. Compared with the controls, individuals with BD died 5 years earlier, more often had comorbidities and thoracic cancer, and had fewer metastases, but did not have shorter delays from cancer diagnosis to death. After matching and adjustment for covariates, individuals with BD more often received palliative care in the last 3 days of life (25% versus 13%, p < .001) and less high-intensity care (e.g., chemotherapy 12% versus 15%, p = .004), but more artificial nutrition (6% versus 4.6%, p = .003). Compared with the schizophrenia comparison group, chemotherapy was received more by individuals with BD in the last 14 days of life (12.5% for BD versus 9.4%, p < .001). CONCLUSIONS: Individuals with BD were more likely to receive palliative care and less likely to receive high-intensity EOL care, except for artificial nutrition. These results may not be specific to BD, as no difference was found between patients with BD and schizophrenia except for chemotherapy.

Feasibility and efficacy of a supervised home-based physical exercise program for metastatic cancer patients receiving oral targeted therapy: study protocol for the phase II/III - UNICANCER SdS 01 QUALIOR trial.

BACKGROUND: Currently, oral targeted therapies are known to be effective and are frequently used to treat metastatic cancer patients, but fatigue is a frequently reported early side effect of these treatments. This fatigue may impact the patient's treatment adherence and result in a negative impact on quality of life. Physical exercise significantly improved the general well-being and quality of life of advanced cancer patients. However, there is no specific physical activity program adapted for patients with advanced disease. METHODS: QUALIOR is a two-part, randomized, open-label, and multicenter with two arms phase II/III trial. Patients (phase II: n = 120; phase III: n = 312) with metastatic cancer (breast cancer, kidney cancer, lung cancer, and other cancers [including but not limited to colon cancer, melanoma, sarcoma, or hepatocarcinoma]) treated with a first- or second-line oral targeted therapy without chemotherapy will be included. Patients will be randomized (2:1) to a 3-month supervised home-based standardized physical activity program or to a recommended adapted physical activity (via a booklet). The primary objective of the phase II is to evaluate the feasibility of the supervised program. The primary objective of the phase III is the evaluation of the benefit of the supervised home-based program compare to the recommended program in terms of fatigue and quality of life at 3 months. The secondary objectives aim to evaluate the impact of the supervised program on fatigue over time, pain, physical capacities, psychosocial and cognitive functions, general quality of life, frequency of dose reduction and patients' adherence to the targeted therapy, overall survival, and progression-free survival. This study will also evaluate the medico-economic impact of supervised program compared to the recommended adapted physical activity program. DISCUSSION: The aim of this study is to evaluate home-based physical exercise program for metastatic cancer patients treated with oral targeted therapies to help patients to cope with fatigue and improve quality of life. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov since May 2017 ( NCT03169075 ).

Distal extremities soft tissue sarcomas: Are they so different from other limb localizations?

BACKGROUND AND OBJECTIVES: Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS). METHODS: From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences. RESULTS: Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence. CONCLUSION: Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype.

Medical staff opposition to a deep and continuous palliative sedation request under Claeys-Leonetti law.

BACKGROUND: For the year 2018, the French government plans a revision of bioethics laws, including certainly the recent Claeys-Leonetti law introducing the right to deep and continuous sedation at the request of palliative patients and prohibiting euthanasia for end-of-life patients. Because there is no published data on medical staff opposition to a deep and continuous palliative sedation request under Claeys-Leonetti law, we believe this report may give insight into physicians' decision making, into the role of criteria for prudent practice, and thus contribute to the bioethical debate. CASE PRESENTATION: We report a 70-year-old patient with squamous cell carcinoma of the hypopharyngeal region, who categorically refused any treatment since one year and asked for deep and continuous palliative sedation until death after attempting suicide. The patient's request was examined and denied by palliative multidisciplinary board, in accordance with by the French Oncology Coordination Centre guidelines. This situation did not fulfil the criteria requested by Claeys-Leonetti law. CONCLUSIONS: As highlighted by the present case-report, patient's expectation regarding palliative sedation can be ambivalent with properly so called euthanasia or assisted suicide. This ambivalent perception was part of the controversy surrounding the parliamentary debate, which is still relevant. This case report supports that deep and continuous sedation under Claeys-Leonetti law need to meet specific criteria defined by the law and documented in the medical files as a safeguard against inappropriate practice. In fact, one of the shortcomings of the current arrangements of Claeys-Leonetti law is a lack of objective medical-based criteria. So it is necessary that scientific peer-reviews papers be published quickly in order to deepen the bioethical debate on the end of life.

Brain Metastases from Adult Sarcoma: Prognostic Factors and Impact of Treatment. A Retrospective Analysis from the French Sarcoma Group (GSF/GETO).

BACKGROUND: Brain metastases (BM) from adult soft tissue or bone sarcomas are rare, and sparse data exist on their prognostic factors and management. SUBJECTS, MATERIALS AND METHODS: A retrospective study was conducted in 15 centers of the French Sarcoma Group, plus one Canadian and one Swiss center, to report on clinical, histological, and treatment characteristics and to identify predictive factors of outcome. RESULTS: Between 1992 and 2012, 246 patients with a median age of 50 years (range: 16-86) were managed for BM. BM included 221 cerebral and cerebellar metastases and 40 cases of meningeal sarcomatosis. The most frequent histopathological subtype was leiomyosarcoma (18.7%). Histological grade was high in 118 (48%) cases. Surgery of BM was carried out for 38 (15.5%) patients. Radiotherapy and chemotherapy were administered in 168 (68.3%) and 91 (37.0%) patients, respectively. Irrespective of treatment modality, BM were controlled in 113 patients (45.9%), including 31 partial responses (12.6%) and 18 complete responses (7.3%). The median overall survival from diagnosis of brain metastasis was 2.7 months (range: 0-133). In the multivariate analysis, the following parameters influenced overall survival: chemotherapy (hazard ratio [HR] = 0.38; 95% confidence interval [CI]: 0.26-0.48), surgery (HR = 0.40; 95% CI: 0.22-0.72), stereotactic radiotherapy (HR = 0.41; 95% CI: 0.19-0.90), whole-brain radiotherapy (HR = 0.51; 95% CI: 0.35-0.76), and grade (HR = 0.65; 95% CI: 0.43-0.98). CONCLUSION: BM of sarcomas are rare and associated with a dismal outcome. Multidisciplinary management with chemotherapy, radiation therapy, and surgery is associated with a better survival. IMPLICATIONS FOR PRACTICE: The incidence of brain and meningeal metastasis in bone and soft tissue sarcomas is estimated between 1% and 8%. Published data are derived from small retrospective case series, often in the pediatric population. A prognostic index is important to guide both clinical decision-making and outcomes research, but one such is lacking for adult sarcoma patients with brain metastases. The current study describes brain metastasis in a large cohort of sarcoma patients. This study, conducted within the French Sarcoma Group, describes the natural history of sarcoma brain metastasis and enables the proposal of strategic recommendations for subsequent clinical trials and for the management of such patients.

Acute myositis: an unusual and severe side effect of docetaxel: a case report and literature review.

Docetaxel is an antimicrotubules cytotoxic agent prescribed widely by medical oncologists in multiple tumor types (breast, lung, prostate, stomach, head, and neck). However, the side effects of docetaxel are numerous (cytopenia, peripheral edema, myalgia, arthralgia, alopecia, and sensitive neuropathy) and recent concerns have been raised about neutropenic enterocolitis in France. Here, we report the case of a 57-year-old patient with metastatic prostatic cancer, who developed a severe myositis and fasciitis grade IV 1 week after his second docetaxel infusion. We reviewed the five cases of docetaxel-related myositis described in the literature, and found that most of them occurred in patients with diabetes (n=5/5) or hypertension (n=4/5). A vascular toxicity may explain this severe complication, and patients with diabetes or hypertension should be monitored closely in the context of a docetaxel chemotherapy.

Dyadic effects of coping strategies, time perspectives, and personality on the quality of life of cancer patients and their caregivers.

OBJECTIVE: Researchers are interested in studying whether the quality of life (QoL) of cancer patients and caregivers is influenced by internal psychobehavioral processes (temporality and coping strategies) and the personality traits that they or their relatives experience. We examined these associations in a sample of patient-caregiver dyads by using the actor-partner interdependence model. METHODS: This cross-sectional study involved 156 cancer patient-caregiver dyads. The self-reported data included QoL (Short-Form 36), coping strategies (Brief Coping Orientation to Problems Experienced Scale), time perspectives (Zimbardo Time Perspective Inventory), and personality (Big Five Inventory). The actor-partner interdependence model was used to test the dyadic effect individualizing actor (degree to which the individual's characteristics were associated with their QoL) and partner (degree to which the individual's characteristics were associated with the QoL of the other dyad member) effects. RESULTS: Actor effects were found for patients and caregivers: The use of positive thinking and future/present-hedonistic perspectives were associated with higher QoL; the use of avoidance and past-negative perspective were associated with lower QoL. Partner effects were also found highlighting the specific mechanisms of the interconnections in the patient-caregiver dyad. The patient's QoL was higher when the caregiver used social support and experienced openness. The caregiver's QoL was lower when the patient used social support and avoidance strategies and experienced future perspective. CONCLUSIONS: The examination of the relationships between individuals' QoL and their internal psychobehavioral processes and personality traits will have several applications in the routine clinical management. Individual-level and dyad-level interventions should be proposed: cognitive-rehabilitation, emotional and cognitive self-regulation for time perspectives, and personality constructs.

Clustering based on unsupervised binary trees to define subgroups of cancer patients according to symptom severity in cancer.

BACKGROUND: Studies have suggested that clinicians do not feel comfortable with the interpretation of symptom severity, functional status, and quality of life (QoL). Implementation strategies of these types of measurements in clinical practice imply that consensual norms and guidelines regarding data interpretation are available. The aim of this study was to define subgroups of patients according to the levels of symptom severity using a method of interpretable clustering that uses unsupervised binary trees. METHODS: The patients were classified using a top-down hierarchical method: Clustering using Unsupervised Binary Trees (CUBT). We considered a three-group structure: "high", "moderate", and "low" level of symptom severity. The clustering tree was based on three stages using the 9-symptom scale scores of the EORTC QLQ-C30: a maximal tree was first developed by applying a recursive partitioning algorithm; the tree was then pruned using a criterion of minimal dissimilarity; finally, the most similar clusters were joined together. Inter-cluster comparisons were performed to test the sample partition and QoL data. RESULTS: Two hundred thirty-five patients with different types of cancer were included. The three-cluster structure classified 143 patients with "low", 46 with "moderate", and 46 with "high" levels of symptom severity. This partition was explained by cut-off values on Fatigue and Appetite Loss scores. The three clusters consistently differentiated patients based on the clinical characteristics and QoL outcomes. CONCLUSION: Our study suggests that CUBT is relevant to define the levels of symptom severity in cancer. This finding may have important implications for helping clinicians to interpret symptom profiles in clinical practice, to identify individuals at risk for poorer outcomes and implement targeted interventions.

Determinants of favorable or unfavorable opinion about euthanasia in a sample of French cancer patients receiving palliative care.

BACKGROUND: Opinion about euthanasia has been explored among the general population and recently in patients receiving palliative care. 96% of the French population declared themselves in favor of euthanasia while less of 50% of palliative care patients are. The aim of the present study was to explore and identify potential determinant factors associated with favorable or unfavorable opinion about euthanasia in a French population of cancer patients receiving palliative care. METHODS: We performed a cross-sectional study among patients in two palliative care units. Eligible patients were identified by the medical staff. Face-to-face interviews were performed by two investigators. Two groups were defined as favorable or unfavorable about euthanasia according to the answer on the specific question about patient opinion on euthanasia. A multivariate analysis including age, belief in God, chemotherapy and gender was built. RESULTS: Seventy-eight patients were interviewed. Median age was 60.5 years (range: 31-87.2). In univariate analysis, patients with a favorable opinion were most often under 60 years old (62 versus 38% unfavorable; p = 0.035), in couple (64 versus 35%; p = 0.032), didn't believe in God (72 versus 28% were non-believers; p < 0.001) and had more frequently an history of chemotherapy treatment (58 versus 42% received at least one cycle of chemotherapy; p = 0.005). In a multivariate analysis, age <  60 years, absence of belief in God and an antecedent of chemotherapy were independently associated with a favorable opinion about euthanasia (OR = 0.237 [0.076-0.746]; p = 0.014, OR = 0.143 [0.044-0.469]; p = 0.001, and OR = 10.418 [2.093-51.853]; p = 0.004, respectively). CONCLUSION: We report here determinants of opinion about euthanasia in palliative care cancer patients. Thus, young patients who do not believe in God and have a history of chemotherapy treatment are more likely to request the discontinuation or restriction of their treatment. A better understanding of these determinants is essential for the development of information and/or interventions tailored to the palliative context.

[An evaluation of hypnosis practices in palliative care.] / Évaluation de la pratique de l'hypnose en soins palliatifs.

There are very few studies in existence today that look at the value of hypnosis in palliative care.The aim of our study was to measure the impact of hypnosis on managing symptoms in palliative care. This quantitative retrospective monocentric observational study evaluated pain and patient satisfaction using monitoring and evaluation sheets, which included a rating scale before and after hypnosis sessions in a palliative care unit.For two years, thirty-seven patients participated in hypnosis sessions mostly for pain (41%) and anxiety (27%). 51% reported a decrease in symptoms, with 35% even reporting that the intensity of their symptoms vanished. Most of the patients were satisfied with the approach and at the end of the study some of them were able to recreate its effects by using self-hypnosis.Despite the small sample, the results confirm those found in the few palliative studies that do exist, particularly relating to the improvement of symptoms such as pain, anxiety, nausea, and respiratory disorders.