Trismus Occurrence and Link With Radiotherapy Doses in Head and Neck Cancer Patients Treated With Chemoradiotherapy.

BACKGROUND: Chemoradiotherapy (CRT) for head and neck cancer (HNC) induces side-effects, including trismus, which impairs quality of life by causing difficulty to eat, speak, and maintain good oral hygiene, and by altering social life. Given the wide variation of reported trismus prevalence and as a first mandatory step for the preventive physiotherapy OPEN program (NCT03979924) this study evaluated trismus occurrence and its link with radiation doses. METHODS: Study population was non-larynx HNC patients with epidermoid carcinoma treated with CRT, with or without surgery. A physiotherapist measured maximal interincisal distance before, during and after CRT, at 10 weeks and 6 months. The proportion of patients with trismus (with a 95% confidence interval) was estimated. Irradiation doses were analyzed between patients with and without trismus using non-parametric Kruskal-Wallis test. RESULTS: We included 45 patients (77.8% male), median age 61 years (range 41-77). The proportion of trismus at baseline was 24.4%, 26.8% at 10 weeks and 37.1% at 6 months. During radiotherapy, it was 27.9% at week 3 and increased to 41.9% at week 6. Trismus occurrence at 10 weeks was higher when the radiation dose to the ipsilateral lateral pterygoid muscle was above the median value, that is, 36.8 grays. CONCLUSION: Trismus occurrence differed according to radiation dose and cancer location. These findings highlight the necessity of early preventive physiotherapy programs to reduce trismus occurrence. The second step, of the interventional multicenter OPEN program, is currently evaluating the impact of preventive physiotherapy and patient education on trismus in a sample of 175 patients.

Hypnosis on patients treated with adjuvant chemotherapy for breast cancer: A feasibility study.

BACKGROUND: Acceptability and tolerance of chemotherapy on patients treated for breast cancer remain challenging. Complementary approaches such as hypnosis may have a favorable impact both at the time of announcing and during chemotherapy, due to the notorious anxiety, distress, and self-perceived dysfunction. The objective of the study was that the patients complied with at least four self-hypnosis sessions out of the six cycles of chemotherapy. METHODS: This open, prospective longitudinal study assessed feasibility of compliance to self-hypnosis during chemotherapy in an outpatients setting. Training sessions were given by a hypnotherapist. Throughout each cycle of chemotherapy, the patient had to use self-hypnosis to better control her anxiety or any difficulties. Nurses could offer help to the patient. Chemotherapy-associated side effects were evaluated through the NCI-Common Toxicity Criteria for Adverse Events v 4.03; moreover, side effects as pain, nausea, vomiting, fatigue, and anxiety were also evaluated during chemotherapy using a visual analogic scale. Health-related quality of life, emotional distress (anxiety and depression), and cancer-related fatigue were assessed (at inclusion, end of chemotherapy and 3 months later) using the EORTC QLQ-C30 and QLQ-BR23, HADS and MFI-20 questionnaires, respectively. The number of patients screened and actually included in the study was reported, as the reasons for refusal. RESULTS: Thirty-five patients were included with a median age of 55 years (35-78). All patients received a hypnosis training session. The overall compliance with self-hypnosis was 68.6% (95% CI: 50.7%-83.2%), meaning that more than two thirds of patients performed at least four sessions of self-hypnosis. According to NCI-CTCAE, Grade 2 nausea and vomiting was observed in 45.7% and 22.9%, respectively, Grade 2 fatigue in 62.9%. Based on the HADS questionnaire, anxiety increased at the end of the chemotherapy and returned to the initial value 3 months later (p = .97) whereas depression significantly decrease 3 months after the end of chemotherapy with respect to the inclusion (p = .003). Role, emotional, and cognitive functioning were slightly affected throughout the treatment, in contrast to dyspnea or physical functioning. CONCLUSION: Our study showed that self-hypnosis was feasible on patients newly diagnosed for breast cancer receiving chemotherapy.

Hypnosis and cognitive behavioral therapy with online sessions to reduce fatigue in patients undergoing chemotherapy for a metastatic colorectal cancer: Rational and study protocol for a feasibility study.

Background: In metastatic colorectal cancer (CRCm), fatigue is pervasive, reduces quality of life, and is negatively associated with survival. Its course is explained in part by psychosocial variables such as emotional distress, coping strategies, or perceived control. Thus, to reduce fatigue, psychosocial interventions appear to be relevant. In some cancers, Cognitive Behavioral Therapies (CBT) reduce fatigue. Hypnosis is also used as a complementary therapy to reduce the side effects of cancer. While CBT requires specific training often reserved for psychologists, hypnosis has the advantage of being increasingly practiced by caregivers and is therefore less expensive (Montgomery et al., 2007). On the other hand, CBT and hypnosis remain understudied in the CRC, do not focus on the symptom of fatigue and in Europe such programs have never been evaluated. Objectives: Implementing an intervention in a healthcare setting is complex (e.g., economic and practical aspects) and recruiting participants can be challenging. The primary objective will therefore be to study the feasibility of two standardized interventions (hypnosis and CBT) that aim to reduce fatigue in patients with CRCm treated in a French cancer center. Methods and design: A prospective, single-center, randomized interventional feasibility study, using mixed methods (both quantitative and qualitative). A total of 60 patients will be allocated to each intervention group [Hypnosis (n = 30) and CBT (n = 30)]. Participants will be randomized into two parallel groups (ratio 1:1). Both programs will consist of 6 weekly sessions focusing on the CRF management over a period of 6 weeks. Trained therapists will conduct the program combining 3 face-to-face sessions and 3 online sessions. The feasibility and experience of interventions will be evaluated by the outcome variables, including the adhesion rate, the reasons for acceptability, relevance or non-adherence, the satisfaction, the fatigue evolution (with ecological momentary assessments), and the quality of life. All questionnaires will be self-assessment using an online application from the cancer center. Discussion: Results will highlight the barriers/facilitators to the implementation of the program and the relevance of the program to the patients, and will be used to generate hypotheses for a randomized control trial. Clinical trial registration: ClinicalTrials.gov Identifier: NCT04999306; https://clinicaltrials.gov/ct2/show/NCT04999306.

Brief Hospital Supervision of Exercise and Diet During Adjuvant Breast Cancer Therapy Is Not Enough to Relieve Fatigue: A Multicenter Randomized Controlled Trial.

Supervised exercise dietary programs are recommended to relieve cancer-related fatigue and weight increase induced by adjuvant treatment of early breast cancer (EBC). As this recommendation lacks a high level of evidence, we designed a multicenter randomized trial to evaluate the impact of an Adapted Physical Activity Diet (APAD) education program on fatigue. We randomized 360 women with EBC who were receiving adjuvant chemotherapy and radiotherapy to APAD or usual care at eight French cancer institutions. Data were collected at baseline, end of chemotherapy, end of radiotherapy, and 6 months post-treatment. The primary endpoint was the general cancer-related fatigue score using the MFI-20 questionnaire. Fatigue correlated with the level of precariousness, but we found no significant difference between the two groups in terms of general fatigue (p = 0.274). The APAD arm has a smaller proportion of patients with confirmed depression at the end of follow-up (p = 0.052). A transient modification in physical activity levels and dietary intake was reported in the experimental arm. However, a mixed hospital- and home-based APAD education program is not enough to improve fatigue caused by adjuvant treatment of EBC. Cancer care centers should consider integrating more proactive diet-exercise supportive care in this population, focusing on precarious patients.

A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX.

BACKGROUND: In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. OBJECTIVES: The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. METHODS: Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. RESULTS: At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P = 0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012). CONCLUSIONS: Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.

[The role of the specialist nurse in parenteral nutrition : An observational study of complications with home parenteral nutrition in adult cancer patients] / Étude observationnelle prospective des complications chez l'adulte atteint de cancer et bénéficiant d'une nutrition parentérale à domicile.

Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks). Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers. Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge. Results : 25 patients were included in the study, with a median age of 63 years [19­74]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [1­6] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [1­85]. A vascular complication (obstruction without thrombosis) was reported in one patient. Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.

Étude observationnelle prospective des complications chez l'adulte atteint de cancer et bénéficiant d'une nutrition parentérale à domicile.

Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks).Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers.Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge.Results : 25 patients were included in the study, with a median age of 63 years [19-74]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [1-6] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [1-85]. A vascular complication (obstruction without thrombosis) was reported in one patient.Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.

Assessing dietary intake in accordance with guidelines: Useful correlations with an ingesta-Verbal/Visual Analogue Scale in medical oncology patients.

BACKGROUND & AIMS: Energy intake and food ingesta are central in nutritional screening and assessment. Cancer patients are at nutritional risk of losing weight, and clinicians need quick and easy tools to identify patients for nutritional support. This study aimed to evaluate the feasibility and the accuracy of a Visual/Verbal Analogue Scale of food ingesta (ingesta-VVAS) to assess energy food intake and nutritional risk in medical oncology patients. METHODS: Dieticians administered prospectively the ingesta-VVAS in 1762 medical oncology patients. The external validity of the ingesta-VVAS was determined against daily energy intake based on a 24-h dietary recall. Patients had to estimate how they currently ate on a scale from 0 "nothing at all" to 10 "as usual". Area Under the Receiver-Operating Characteristics (ROC) curve served as determine the optimal cut-off and provide the discriminative power of the tool to detect patients who ingested less or more than 25 kcal kg-1 day-1. RESULTS: The feasibility of the ingesta-VVAS was 97.7%. The scores were significantly correlated with energy intake (ρ = .67, p < .05), whatever the specific situation (i.e. malnutrition or not). With a cut-off of ≤7, the ingesta-VVAS exhibited a good power discrimination (AUC = .804) to detect patients who ingested less or more than 25 kcal kg-1 day-1, with a sensitivity of 80.8%, a positive predictive value of 83.6%, a specificity of 67.5%, and a negative predictive value of 63.3%. Patients with a score ≤7 on the ingesta-VVAS score were at 12-fold higher probability of nutritional risk [OR 12.3; 95% CI (8.7-17.4); p < .001]. Sensitivity to detect patients with a significant weight loss was 71%, and a positive predictive value of 75.9%. CONCLUSIONS: This easy-to-use ingesta-VVAS is well-correlated with energy intake and may be useful in clinical practice. An ingesta-VVAS score is ≤ 7 could be used to detect patients with nutritional risk of weight loss in medical oncology.

Effects of a Hypnosis Session Before General Anesthesia on Postoperative Outcomes in Patients Who Underwent Minor Breast Cancer Surgery: The HYPNOSEIN Randomized Clinical Trial.

Importance: Hypnosis is now widespread in medical practice and is emerging as an alternative technique for pain management and anxiety. However, its effects on postoperative outcomes remain unclear. Objective: To evaluate the efficacy of a preoperative hypnosis session for reducing postoperative breast pain in patients who underwent minor breast cancer surgery. Design, Setting, and Participants: The HYPNOSEIN prospective randomized clinical trial was conducted from October 7, 2014, to April 5, 2016. In this multicenter study in France, 150 women scheduled for minor breast cancer surgery were randomized between control and hypnosis arms, and 148 (71 control and 77 hypnosis) were included in the intent-to-treat analysis. Intervention: On the day of surgery, eligible patients were randomly assigned (1:1) to the control arm or the hypnosis arm. Patients (but not the care teams) were blinded to the arm to which they were assigned. A 15-minute hypnosis session before general anesthesia in the operating room was performed in the hypnosis arm. Main Outcomes and Measures: The primary end point was breast pain reduction (by 2 on a visual analog scale), assessed immediately before discharge from the postanesthesia care unit (PACU). Secondary end points were nausea/vomiting, fatigue, comfort/well-being, anxiety, and PACU length of stay, assessed at different times until postoperative day 30. Results: The median patient age was 57 years (range, 33-79 years) in the control arm and 53 years (range, 20-84 years) in the hypnosis arm. Baseline characteristics were similar in the 2 arms. The median duration of the hypnosis session was 6 minutes (range, 2-15 minutes). The use of intraoperative opioids and hypnotics was lower in the hypnosis arm. The mean (SD) breast pain score (range, 0-10) was 1.75 (1.59) in the control arm vs 2.63 (1.62) in the hypnosis arm (P = .004). At PACU discharge and with longer follow-up, no statistically significant difference in breast pain was reported. Fatigue was significantly lower in the hypnosis arm on the evening of surgery (mean [SD] score, 3.81 [2.15] in the control arm vs 2.99 [2.56] in the hypnosis arm; P = .03). The median PACU length of stay was 60 minutes (range, 20-290 minutes) in the control arm vs 46 minutes (range, 5-100 minutes) in the hypnosis arm (P = .002). Exploratory analyses according to patient perception of whether she received hypnosis showed significantly lower fatigue scores in the perceived hypnosis subgroup on the evening of surgery (mean [SD], 4.13 [2.26] for no perceived hypnosis vs 2.97 [2.42] for perceived hypnosis; P = .01). Anxiety was also significantly lower on the evening of surgery in the perceived hypnosis subgroup (mean [SD], 0.75 [1.64] for perceived hypnosis vs 1.67 [2.29] for no perceived hypnosis; P = .03). Conclusions and Relevance: The results of this study do not support a benefit of hypnosis on postoperative breast pain in women undergoing minor breast cancer surgery. However, other outcomes seem to be improved, which needs to be confirmed by further studies. Trial Registration: EudraCT Identifier: 2014-A00681-46 and ClinicalTrials.gov Identifier: NCT03253159.

Management of Cancer Cachexia and Guidelines Implementation in a Comprehensive Cancer Center: A Physician-Led Cancer Nutrition Program Adapted to the Practices of a Country.

CONTEXT: Cancer-associated cachexia is correlated with survival, side-effects, and alteration of the patients' well-being. OBJECTIVES: We implemented an institution-wide multidisciplinary supportive care team, a Cancer Nutrition Program (CNP), to screen and manage cachexia in accordance with the guidelines and evaluated the impact of this new organization on nutritional care and funding. METHODS: We estimated the workload associated with nutrition assessment and cachexia-related interventions and audited our clinical practice. We then planned, implemented, and evaluated the CNP, focusing on cachexia. RESULTS: The audit showed a 70% prevalence of unscreened cachexia. Parenteral nutrition was prescribed to patients who did not meet the guideline criteria in 65% cases. From January 2009 to December 2011, the CNP team screened 3078 inpatients. The screened/total inpatient visits ratio was 87%, 80%, and 77% in 2009, 2010, and 2011, respectively. Cachexia was reported in 74.5% (n = 2253) patients, of which 94.4% (n = 1891) required dietary counseling. Over three years, the number of patients with artificial nutrition significantly decreased by 57.3% (P < 0.001), and the qualitative inpatients enteral/parenteral ratio significantly increased: 0.41 in 2009, 0.74 in 2010, and 1.52 in 2011. Between 2009 and 2011, the CNP costs decreased significantly for inpatients nutritional care from 528,895€ to 242,272€, thus financing the nutritional team (182,520€ per year). CONCLUSION: Our results highlight the great benefits of implementing nutritional guidelines through a physician-led multidisciplinary team in charge of nutritional care in a comprehensive cancer center.

Meal context and food preferences in cancer patients: results from a French self-report survey.

PURPOSE: The present study examined patient self-reports of descriptions, experiences and consequences of meal disturbances and food preferences within a cultural context (i.e., French meal traditions) in various treated cancer patients along their disease trajectory. METHODS: Over 800 questionnaires were sent to 20 cancer treatment centres in France. During a 9-month period, 255 questionnaires were received from five centres. Inclusion criteria included those French patients over 18 years of age, could read and understand French, had an Eastern Cooperative Oncology Group score between 0 and 2, experienced treatment-induced nutrition changes and/or had decreased oral intake. Dietetic staff assessed clinical characteristics while patients completed a 17-item questionnaire. RESULTS: The majority of patients were diagnosed with breast, gastro-intestinal (GI) tract and head and neck cancers (62 %). Half of the patients (49 %) experienced weight loss >5 %. The main treatment-induced side effects were fatigue, nausea, dry mouth, hypersensitivity to odors and GI tract transit disorders. These discomforts affected eating and drinking in 83 % of patients, inducing appetite loss and selected food aversion. Food preference appeared heterogeneous. Food taste, odor and finally appearance stimulated appetite. Finally, dietary behaviors and satisfaction were driven by the extent to which food was enjoyed. CONCLUSIONS: During oncologic treatments, eating and drinking were affected in more than three-quarters of patients. As recommended by practice guidelines, nutritional assessment and follow-up are required. Personalized nutritional counseling should include the role of the family, patient's meal traditions, and food habits.

A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm.

BACKGROUND: Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. AIMS: The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-ß2 (TGF-ß2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. PATIENTS AND METHODS: We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect(®) (CP) or a control isocaloric diet (without TGF-ß2 or glutamine). RESULTS: Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3-4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3-4 hematological toxicities or reasons for treatment interruption. CONCLUSION: This randomized study does not support the hypothesis that oral glutamine and TGF-ß2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm.

Adapted physical activity and diet (APAD) during adjuvant breast cancer therapy: design and implementation of a prospective randomized controlled trial.

Exercise practice and appropriate nutrition have been advanced as non pharmacological supportive care to reduce side effects related to cancer and its treatment, but large sample-sized randomized controlled trials are needed to confirm such results. The Adapted Physical Activity and Diet counseling (APAD) study is a prospective randomized controlled trial designed to evaluate the effectiveness of a 26-week hospital- and home-based lifestyle intervention on cancer-related fatigue in women receiving breast cancer adjuvant treatment (chemotherapy and radiotherapy). The aim of this paper is to describe the APAD study protocol. Study recruitment goal is 264 adult breast cancer women with newly, histologically proven, incident and non metastatic breast cancer scheduled for 6 cycles of adjuvant chemotherapy followed by radiotherapy. Patients are randomized either in the experimental arm with tailored exercise training and diet counseling program or in the control arm without any lifestyle intervention (usual care). Outcome measures are collected at baseline, and at 15 weeks (i.e., mid-intervention), 26 weeks (i.e., immediately post-intervention), and at 12-month and 18-month of follow-up. Intervention effect is assessed on fatigue (emotional, cognitive, physical), quality-of-life, anxiety, depression, body weight and composition. In addition, levels of physical activity, dietary intakes and adjuvant therapy observance are measured and a cost-utility analysis will be performed. If improvements in fatigue, quality-of-life and a better weight control are observed, the APAD study could demonstrate the feasibility and the effectiveness of such exercise and nutrition supportive care with limited additional cost in patients receiving adjuvant breast cancer therapy.