Head and neck cancer patients treated with concomitant chemoradiotherapy involving the oral cavity and oropharynx: is another choice possible than prophylactic gastrostomy?

PURPOSE OF REVIEW: Recent recommendations on cachexia highlight, in head and neck cancers, the heterogeneity of studies, focusing on weight loss and sequelae including swallowing disorders. The current national guidelines emphasize that, in cases of concurrent chemoradiotherapy (cCRT) involving the oral cavity and oropharynx, prophylactic gastrostomy placement should be carried out systematically. We review why this technique is particularly relevant in this specific location for the feasibility of cCRT. RECENT FINDINGS: A randomized trial is underway on swallowing disorders and the quality of life of patients after prophylactic vs. reactive gastrostomy in advanced oropharyngeal cancer patients treated with CRT. Concurrently, recent literature reviews emphasize the importance of the cumulative dose of chemotherapy for local control and survival. In cases of cCRT involving the oral cavity or the oropharynx, nutritional support could have a beneficial or detrimental impact on chemotherapy. SUMMARY: Specifically for patients treated with cCRT involving the oral cavity and oropharynx, prophylactic gastrostomy would be able to fulfill the three objectives of local control, survival, and quality of life, minimizing complications related to nutritional support. Studies need to be more homogeneous. In clinical practice, nutrition should primarily assist in carrying out cancer treatment when survival is the main goal.

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.

[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.

Short- and long-term impact of adapted physical activity and diet counseling during adjuvant breast cancer therapy: the "APAD1" randomized controlled trial.

BACKGROUND: Patients with breast cancer undergoing chemotherapy and radiotherapy experience fatigue and other treatment side effects. Integrative therapies combining physical activity and dietary counseling are recommended; however to date no large randomized controlled trial has been conducted during adjuvant therapy. The Adapted Physical Activity and Diet (APAD) intervention was evaluated for its ability to decrease fatigue (primary outcome), anxiety, depression, body mass index (BMI), and fat mass, and enhance muscular and cognitive performances, and quality-of-life (QoL). METHODS: Women diagnosed with early breast cancer (N = 143, mean age = 52 ± 10 years) were randomized to APAD or usual care (UC). APAD included thrice-weekly moderate-intensity mixed aerobic and resistance exercise sessions and 9 dietetic consultations. Patient-reported outcomes (PROs) and anthropometric, muscular, and cognitive variables were measured at baseline, 18 weeks (end of chemotherapy), and 26 weeks (end of radiotherapy and intervention), and at 6- and 12-month post-intervention follow-ups. Multi-adjusted linear mixed-effects models were used to compare groups over time. RESULTS: Significant beneficial effects of the APAD intervention were observed on all PROs (i.e., fatigue, QoL, anxiety, depression) at 18 and 26 weeks. The significant effect on fatigue and QoL persisted up to 12-month follow-up. Significant decreases in BMI, fat mass, and increased muscle endurance and cognitive flexibility were observed at 26 weeks, but did not persist afterward. Leisure physical activity was enhanced in the APAD group vs UC group at 18 and 26 weeks. No significant effect of the intervention was found on major macronutrients intake. CONCLUSIONS: A combined diet and exercise intervention during chemotherapy and radiotherapy in patients with early breast cancer led to positive changes in a range of psychological, physiological and behavioral outcomes at the end of intervention. A beneficial effect persisted on fatigue and QoL at long term, i.e., 1 year post-intervention. Diet-exercise supportive care should be integrated into the management of early breast cancer patients. TRIAL REGISTRATION: The APAD study was prospectively registered on ClinicalTrials.gov (NCT01495650; date of registration: December 20, 2011).

Patient-centeredness to anticipate and organize an end-of-life project for patients receiving at-home palliative care: a phenomenological study.

BACKGROUND: The development of end-of-life primary care is a socio-medical and ethical challenge. However, general practitioners (GPs) face many difficulties when initiating appropriate discussion on proactive shared palliative care. Anticipating palliative care is increasingly important given the ageing population and is an aim shared by many countries. We aimed to examine how French GPs approached and provided at-home palliative care. We inquired about their strategy for delivering care, and the skills and resources they used to devise new care strategies. METHODS: Twenty-one GPs from the South of France recruited by phone according to their various experiences of palliative care agreed to participate. Semi-structured interview transcripts were examined using a phenomenological approach inspired by Grounded theory, and further studied with semiopragmatic analysis. RESULTS: Offering palliative care was perceived by GPs as a moral obligation. They felt vindicated in a process rooted in the paradigm values of their profession. This study results in two key findings: firstly, their patient-centred approach facilitated the anticipatory discussions of any potential event or intervention, which the GPs openly discussed with patients and their relatives; secondly, this approach contributed to build an "end-of-life project" meeting patients' wishes and needs. The GPs all shared the idea that the end-of-life process required human presence and recommended that at-home care be coordinated and shared by multi-professional referring teams. CONCLUSIONS: The main tenets of palliative care as provided by GPs are a patient-centred approach in the anticipatory discussion of potential events, personalized follow-up with referring multi-professional teams, and the collaborative design of an end-of-life project meeting the aspirations of the patient and his or her family. Consequently, coordination strategies involving specialized teams, GPs and families should be modelled according to the specificities of each care system.

Reproductive Decision-Making in MMR Mutation Carriers After Results Disclosure: Impact of Psychological Status in Childbearing Options.

Reproductive techniques such as prenatal diagnosis (PND) or preimplantation genetic diagnosis (PGD), although debated, are legally forbidden in France in case of Lynch syndrome. The preference of mutation carriers about their reproductive options is not systematically considered in France. We aimed to prospectively assess the reproductive preferences of mismatch repair mutation carriers consulting in our institution (2003-2010, n = 100). We also considered the short- and long-term post-disclosure psychological impact using the Impact of Events Scale-Revised questionnaire to measure the prevalence of posttraumatic stress disorder (PTSD) in those patients. Complete data were obtained for 34 respondents (17 males, 17 females, median age of 33.5 years [22-59]). Seventeen respondents (57 %) preferred spontaneous natural conception versus 28 % and 35 % choosing PND and PGD, respectively. At results disclosure, respondents mainly explained their distress by fear of premature death (43 %) and transmitting mutated genes (42 %). One year later, this last fear remained predominant in 55 % of subjects. None of the main socio-demographical, psychological or medical variables (including fear of transmitting mutations) was significantly associated with the reproductive preferences. Results disclosure had a real and time-decreasing psychological impact on mutation carriers. Reproductive techniques, expected to decrease the hereditary risk, were not significantly preferred to natural conception.

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.

Identification of 18F-FDG PET/CT Parameters Associated with Weight Loss in Patients with Esophageal Cancer.

18F-FDG PET-CT is routinely performed as part of the initial staging of numerous cancers. Other than having descriptive, predictive and prognostic values for tumors, 18F-FDG PET-CT provides full-body data, which could inform on concurrent pathophysiological processes such as malnutrition. To test this hypothesis, we measured the 18F-FDG uptake in several organs and evaluated their association with weight loss in patients at diagnosis of esophageal cancer. Forty-eight patients were included in this retrospective monocentric study. 18F-FDG uptake quantification was performed in the brain, the liver, the spleen, bone marrow, muscle and the esophageal tumor itself and was compared between patients with different amounts of weight loss. We found that Total Lesion Glycolysis (TLG) and peak Standardized Uptake Values (SUVpeak) measured in the brain correlated with the amount of weight loss: TLG was, on average, higher in patients who had lost more than 5% of their usual weight, whereas brain SUVpeak were, on average, lower in patients who had lost more than 10% of their weight. Higher TLG and lower brain SUVpeak were associated with worse OS in the univariate analysis. This study reports a new and significant association between 18F-FDG uptake in the brain and initial weight loss in patients with esophageal cancer.

Immunonutrition before and during radiochemotherapy: improvement of inflammatory parameters in head and neck cancer patients.

PURPOSE: Inflammatory, angiogenic and oxidative stress markers have been explored in head and neck squamous cell carcinoma (HNSCC) patients before and during radiochemotherapy. Furthermore, the effects of an oral supplementation containing amino acids, ω-3 fatty acids, ribonucleic acids, vitamins, and antioxidants on biological markers and acute toxicities were investigated. METHODS: Thirty-one patients with non-metastatic stage III or IV HNSCC treated with concomitant radiochemotherapy were recruited. A nutritional support (Oral Impact) was given during 5 days before each cycle of chemotherapy. Biological samples were collected at baseline, after 5 days of oral supplementation and before the last cycle of chemotherapy. Acute phase proteins levels, proteomic cytokines determination and urinary isoprostanes levels were used as inflammatory and oxidative stress biomarkers. Toxicities were followed up during radiochemotherapy. RESULTS: At baseline, median levels of inflammatory (CRP 9.8 mg/l [0.8-130.1], IL-6 4.2 pg/ml [0.7-126.5]), pro-angiogenic (VEGF 229.5 pg/ml [13.1-595.9]) and pro-oxidative stress (urinary isoprostanes 118 pmol/mmol creatinine [51-299]) markers were increased. Decrease in CRP (p = 0.002) and α-1 acid glycoprotein (p = 0.020) levels were observed after 5 days of oral supplementation. During radiochemotherapy, no significant variation of inflammatory markers was reported, and a low incidence of severe acute mucositis was noted. CONCLUSIONS: Stage III or IV HNSCC patients are characterised by a pro-inflammatory, pro-angiogenic and pro-oxidative status. Nutritional support could improve this inflammatory state and could prevent severe acute mucositis.

Validation of a surgical technique for rat intestinal irradiation: potential side effects prevention by dietary grape phenolics.

AIMS: This study evaluates and defines the histological and biochemical consequences of irradiation on the Hauer-Jensen intestinal model and investigates the potential effects of dietary polyphenols. MAIN METHODS: Sprague-Dawley rats were orchiectomized, and an ileal loop was transposed to the left part of the scrotum, then irradiated 2 weeks after surgery with a single dose of 21 Gy (4.49 Gy/min). Four groups of rats received either phenolic extracts from grape seeds (EGS) and from red wine (ACYS, EGT), or pure quercetin 3-O-ß-glucoside (Q3G), for 5 days before the irradiation and were sacrificed 2 weeks after. Antioxidant enzyme activities, i.e. superoxide dismutase (SOD) and glutathione peroxidase activity (GSHPx), and oxidative markers such as myeloperoxidase activity (MPO) and thiobarbituric acid reactive substances (MDA) were measured as well as cytokine-induced neutrophil chemoattractant level (CINC-1), a chemokine involved in inflammation. KEY FINDINGS: Irradiated rats exhibited a high radiation injury score (RIS) with a thickened serosa, mucosal loss and ulceration, and epithelial atypicality. Intestinal MPO activity and CINC-1 concentration were significantly increased in irradiated animals (60 and 66 %, respectively). Higher plasma MDA levels (58 %) and SOD activity (32 %) were accompanied by a reduced GSHPx activity (79 %). However, feeding phenolic extracts remarkably reduced levels of blood SOD activity (34 % on average), intestinal CINC-1 (25-75 % range) and MPO activity (36-84 %). Except for Q3G, phenolics preserved the intestinal structure. SIGNIFICANCE: These findings show that irradiation triggers an inflammation, and an oxidative stress by disturbing the pro-oxidant/antioxidant balance and indicate that phenolics supply exerts preventive effects against radio-induced intestinal impairment.

[Non-pharmalogical interventions and breast cancer: What benefit in addition to radiotherapy?] / Interventions non médicamenteuses et cancer du sein : quel bénéfice en complément d'une radiothérapie ?

Adjuvant radiotherapy is one of the major anticancer treatments in early breast cancer patients. Acute and late radio-induced effects may occur during or after breast cancer radiotherapy, and their medical management is a major issue for radiation oncologists. Here, the present review of literature embraces complementary non-pharmacological interventions, which could be combined to adjuvant radiotherapy in order to improve patients care.

EGFR and HER3 mRNA expression levels predict distant metastases in locally advanced rectal cancer.

Aberrant activation of the HER signaling pathways plays a critical role in the invasive and metastatic potential of tumors. The aim of this study was to address whether, in rectal cancer, alterations of these pathways could have a value as prognostic factors to be used to identify patients who are at risk of distant metastases. Therefore, the mRNA expression of the four members of the HER family as well as the frequency of PTEN allelic loss and KRAS/BRAF mutations were determined in pretreatment biopsies from a series of 100 locally advanced rectal cancers and then their ability to predict distant metastases was evaluated. Over-expression of EGFR (p = 0.021), HER2 (p = 0.011) and HER3 (p = 0.020) was significantly associated with worse metastasis-free survival in univariate analysis. In multivariate analysis, both over-expression of EGFR (p = 0.028) and HER3 (p = 0.011) remained independent prognostic factors for distant metastasis. In conclusion, quantification of EGFR and HER3 mRNA expression in pretreatment biopsies may be useful to identify patients who are at risk of developing metastases.

Importance of Patient Education for At-home Yoga Practice in Women With Hormonal Therapy-induced Pain During Adjuvant Breast Cancer Treatment: A Feasibility Study.

BACKGROUND: Osteo-articular pain (OAP) is experienced by approximately 50% of women under hormonal therapy (HT) for breast cancer (BC), which increases the risk for therapy discontinuation. This study was aimed to assess benefits of yoga practice combined with patient education (PE) for at-home practice by evaluating feasibility among BC patients under HT and measuring OAP, flexibility and satisfaction. METHODS: Feasibility was evaluated by patient adherence as accomplishment of at least 4 out of 6 supervised yoga-PE sessions along with 70% or more at-home yoga sessions. Intervention (12 weeks) included two 6-weeks periods: P1 comprising one 90-minutes supervised yoga-PE session/week and 15-minutes daily at-home yoga and P2, daily autonomous at-home yoga sessions. Evaluations (at inclusion and by the end of each period) consisted in assessment of OAP on Visual Analog Scale (VAS), forward flexibility (cm) and patient satisfaction on Likert (0-10 points) scale. RESULTS: Between September 2018 and May 2019 we included 24 patients of median 53 years (range 36-72). Feasibility was validated by 83% successful adherence rate. Pain was significantly reduced from median VAS of 6 [range 4-10] to 4 [range 0-7] at the end of both P1 and P2 (p < 0.01), albeit with no difference between P1 and P2. Forward flexibility improved by a median gain of 8 cm (end of P2) and median satisfaction score of 10/10 [range 8-10]. CONCLUSION: Combined physiotherapy-yoga-PE intervention is a feasible strategy to increase at-home yoga practice with potential benefit on pain, flexibility, and satisfaction, thus prompting further evaluations in larger randomized multicenter trials. CLINICALTRIALS.GOV: NCT04001751.

Diagnostic criteria for cancer cachexia: reduced food intake and inflammation predict weight loss and survival in an international, multi-cohort analysis.

BACKGROUND: Cancer-associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C-reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer-associated WL (primary endpoint) and overall survival (OS, secondary endpoint). METHODS: The data set included a total of 12,253 patients at risk for cancer-associated WL. Patient-reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively. RESULTS: Patients had a mean weight change of -7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5-5.9% (19.7%), 6.0-10.0% (23.2%), 11.0-14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P < 0.0001) if food intake was moderately [OR 6.28, 95% confidence interval (CI 5.28-7.47)] or severely reduced [OR 18.98 (95% CI 15.30-23.56)]. In subset analysis, adjusted for food intake, CRP was independently associated (P < 0.0001) with ≥15% WL [CRP 10-100 mg/L: OR 2.00, (95% CI 1.58-2.53)] and [CRP > 100 mg/L: OR 2.30 (95% CI 1.62-3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5-10.3), with median follow-up of 39.7 months (95% CI 38.8-40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001). CONCLUSIONS: Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer-associated cachexia.

Cancer-Associated Malnutrition and CT-Defined Sarcopenia and Myosteatosis Are Endemic in Overweight and Obese Patients.

BACKGROUND: Overweight/obese patients' large fat mass can mask the loss of skeletal muscle, which is associated with mortality in the oncology setting. We investigated the prevalence of computed tomography (CT)-defined sarcopenia and myosteatosis across different levels of nutrition risk assessed by the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF). We also evaluated whether the PG-SGA SF, sarcopenia, and myosteatosis were prognostic of overall survival. METHODS: This was a prospective, observational study. Consecutive patients with body mass index ≥25.0 kg/m2 with newly diagnosed head and neck cancer (any stage) or lung and gastrointestinal tract cancer (locally recurrent or metastatic) were screened at presentation to oncology clinics. Nutrition risk was assigned based on PG-SGA SF triage recommendations. Based on CT, patients were classified with sarcopenia and/or myosteatosis using published cutoffs. Survival analyses were conducted. RESULTS: Patients (n=1157) were 63.6 ± 11.4 years, 64% male, and 61% had stage IV disease. Sarcopenia and myosteatosis were prevalent across PG-SGA SF nutrition risk categories (scores 0-1 [no risk; 36% sarcopenic; 44% myosteatotic], scores 2-3 [37%; 37%], scores 4-8 [40%; 41%], and scores ≥9 [high risk; 50%; 49%]). In multivariable survival analysis, PG-SGA SF scores ≥9 (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.66-2.60, P<0.001), sarcopenia (HR 1.25, 95% CI 1.06-1.46, P=0.006), and myosteatosis (HR 1.25, 95% CI 1.07-1.46, P<0.001) independently predicted reduced survival. CONCLUSION: CT-defined sarcopenia and myosteatosis are prevalent across different levels of nutrition risk in overweight/obese patients with cancer. Assessment of skeletal muscle using CT adds prognostic value to the PG-SGA SF.

[Exercise and cancer: Evidence of efficacy during and after treatments]. / Activités physiques et cancers : des bénéfices prouvés pendant et après les traitements.

After a brief semantic and historical presentation, the article presents the main trials and systematic reviews on the tertiary prevention and care of cancers through physical activity. It gives the keys to understanding how, in forty years of research, interventions dedicated to prevent physical inactivity to reduce the risk of cancer have become as indispensable as adapted physical activity (APA) programs for care pathways. If the public health message "move more" with or without cancer remains true, the research encourages practitioners to implement personalized programs in primary prevention, in addition to treatment and prevention of recurrence. As soon as the diagnosis is made, APA programs will become truly supportive care complementary of treatments, in other words non-pharmacological interventions (NPIs), with the aim of improving the quality of life of patients, improving their overall health, reducing side effects of treatment, potentiate the effects of certain treatments, and reduce the risk of recurrence. Research remains to be carried out notably on the survival, on the advanced cancers and on the integrative modelling of the mechanisms involved.

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.

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.