Extranodal nasal-type NK/T lymphoma treated with chemotherapy and radiotherapy: case series from a European tertiary referral center and review of the literature.

PURPOSE: Extranodal nasal-type NK/T-cell lymphoma (ENKTL) is very rare in western countries and few data are available regarding the prognosis and the outcome of patients treated for this disease. We aimed to evaluate the prognosis, the pattern and risk factors of disease failure after combined therapy and also performed a review of the literature. PATIENTS AND METHODS: We retrospectively analyzed 20 patients with (ENKTL) who underwent L­Asparaginase based chemotherapy followed by (chemo-) radiotherapy between 2010 and 2020 in our center. Data on clinical characteristics and irradiation were collected. Failure patterns were recorded as local (tumor site), regional (regional lymph nodes) or distant failure (metastasis and/or nonregional lymph nodes). RESULTS: During a median follow-up period of 46 months, disease failure was observed in 8 patients (40%). The 3­year progression-free survival (PFS) and overall survival (OS) rates were 62.5 and 83.0%, respectively. The failure patterns were local (n = 6, 30%), regional (n = 3, 15%) and distant (n = 4, 20%). Among patients with local failure, all failures occurred within the radiation fields (100%). Univariate analysis showed that bilateral regional lymph node involvement (p = 0.0002), initial circulating EBV viral load ≥ 3.5 log (p = 0.03) and no negativation of EBV PCR after induction CT (p = 0.0497) were independent predictors of PFS. CONCLUSION: Patients with bilateral lymph node involvement and/or high EBV viral load have a significant recurrence rate despite multimodal therapy. These results need to be confirmed by larger studies. Given the high rate of local recurrence within radiotherapy fields, the value of dose escalation should be considered. Patients at risk of relapse should be included in dedicated trials.

Impact of the COVID-19 pandemic on clinical presentation, treatments, and outcomes of new breast cancer patients: A retrospective multicenter cohort study.

BACKGROUND: The SARS CoV-2 pandemic disrupted healthcare systems. We compared the cancer stage for new breast cancers (BCs) before and during the pandemic. METHODS: We performed a retrospective multicenter cohort study on the data warehouse of Greater Paris University Hospitals (AP-HP). We identified all female patients newly referred with a BC in 2019 and 2020. We assessed the timeline of their care trajectories, initial tumor stage, and treatment received: BC resection, exclusive systemic therapy, exclusive radiation therapy, or exclusive best supportive care (BSC). We calculated patients' 1-year overall survival (OS) and compared indicators in 2019 and 2020. RESULTS: In 2019 and 2020, 2055 and 1988, new BC patients underwent cancer treatment, and during the two lockdowns, the BC diagnoses varied by -18% and by +23% compared to 2019. De novo metastatic tumors (15% and 15%, p = 0.95), pTNM and ypTNM distributions of 1332 cases with upfront resection and of 296 cases with neoadjuvant therapy did not differ (p = 0.37, p = 0.3). The median times from first multidisciplinary meeting and from diagnosis to treatment of 19 days (interquartile 11-39 days) and 35 days (interquartile 22-65 days) did not differ. Access to plastic surgery (15% and 17%, p = 0.08) and to treatment categories did not vary: tumor resection (73% and 72%), exclusive systemic therapy (13% and 14%), exclusive radiation therapy (9% and 9%), exclusive BSC (5% and 5%) (p = 0.8). Among resected patients, the neoadjuvant therapy rate was lower in 2019 (16%) versus 2020 (20%) (p = 0.02). One-year OS rates were 99.3% versus 98.9% (HR = 0.96; 95% CI, 0.77-1.2), 72.6% versus 76.6% (HR = 1.28; 95% CI, 0.95-1.72), 96.6% versus 97.8% (HR = 1.09; 95% CI, 0.61-1.94), and 15.5% versus 15.1% (HR = 0.99; 95% CI, 0.72-1.37), in the treatment groups. CONCLUSIONS: Despite a decrease in the number of new BCs, there was no tumor stage shift, and OS did not vary.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Ten-Year Outcomes of Hypofractionated Postmastectomy Radiation Therapy of 26 Gy in 6 Fractions.

PURPOSE: To investigate the efficacy and long-term side effects of hypofractionated postmastectomy radiation therapy (HFRT-PM) of 26 Gy in 6 fractions over 5 weeks. METHODS AND MATERIALS: We retrospectively reviewed characteristics and outcomes of patients with stage I to III breast cancer treated with HFRT-PM between 2000 and 2009. Treatment provided 4 fractions of 4 Gy (days 1, 3, 15, 17) and then 2 fractions of 5 Gy (days 29 and 31) over 5 weeks. The treatment techniques were applied by using 3-dimensional conformal radiation therapy of the chest wall with regional nodal volume if required. RESULTS: We identified 454 patients with a median follow-up of 10.6 years (range, 0.5-22.9). Regional nodal irradiation was done in 84.1% of patients. At 10 years, the cumulative incidence of locoregional relapse was 15.1%. In multivariate analysis, regional lymph node involvement (≥4 nodes) was associated with worse locoregional control (hazard ratio, 1.68; 95% confidence interval, 1.06-2.67; P = .03) and overall survival (hazard ratio, 2.16; 95% confidence interval, 1.59-2.95; P < .001). The toxicities were acceptable. The incidence of cardiac disorders (3.3%), and symptomatic lung fibrosis (1.5%) was low during follow-up. At 10 years, the cumulative rate of arm lymphedema was 9.5% and considered severe in 20 patients (4.4%). CONCLUSIONS: The long-term results of this study show that HFRT-PM of 26 Gy in 6 fractions over 5 weeks seems safe, but locoregional recurrence seems slightly higher than that observed in the literature, highlighting the need for long-term follow-up and for randomized trials for hypofractionated radiation therapy postmastectomy.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease which is often associated with Helicobacter pylori (H. pylori) infection. First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H. pylori. The presence of H. pylori resistance factors such as translocation t (11;18), peri-gastric lymph node involvement and the degree of tumor infiltration of the gastric wall; or lack of response to antibiotic therapy are two main indications to treat with definitive radiotherapy (RT). RT is an effective treatment in localized gastric MALT lymphoma. A moderate dose of 30 Gy allows a high cure rate while being well tolerated. After treatment, regular gastric endoscopic follow-up is necessary to detect a potential occurrence of gastric adenocarcinoma.

Adult parameningial alveolar rhabdomyosarcoma: Case report and literature review.

Alveolar rhabdomyosarcoma (ARMS) represents the most common childhood soft tissue sarcoma, but they are rarely seen among adults. Most of the protocols for adults are adapted from pediatric protocols. Here we report a case of a 53-year-old woman diagnosed with a nasal alveolar rhabdomyosarcoma, stage IV at diagnosis, treated by chemotherapy (a regimen inspired from the pediatric protocole pEpSSG RMS 2005) which led to partial response followed by chemo-radiotherapy. We performed a systematic review of adult head and neck ARMS and found 29 cases. Primary chemotherapy with different protocols (VAC, VAI or VIE) should be done followed by surgery and/or external beam radiotherapy (preferably with IMRT). EBRT seems beneficial to every ARMS with a dose around 50Gy in a conventional fractionation, eventually completed with a boost on residual tumor. The target volume must be defined on pre-chemotherapy imaging. Brachytherapy and proton therapy are under evaluation.

Impact of tobacco smoking on the patient's outcome after (chemo)radiotherapy for anal cancer.

PURPOSE: Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer. METHODS: We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival (OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS). RESULTS: Patients' characteristics were as follows: median age, 62 years (range = 36-89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86 patients (50%), among whom 28 patients and 58 patients were current and former smokers, respectively. Tumours were classified as locally limited (T1-2, N0, M0) for 86 patients (50%) and locally advanced (T3-4 or N+, M0) for 85 patients (50%). The median total dose was 64.4 Gy (range = 54-76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4 cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio = 2.85, 95% confidence interval [1.25-6.50], p = 0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p = 0.038). Tobacco smoking was also associated with poor overall survival (p = 0.03), locoregional relapse-free survival (LRFS; p = 0.05) and CFS (p = 0.02). CONCLUSIONS: Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose ± chemotherapy.

Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC.

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13-3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07-3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36-3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05-3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

Sarcopenia: An important prognostic factor for males treated for a locally advanced esophageal carcinoma.

INTRODUCTION: Sarcopenia is a prognostic factor of esophageal carcinoma (EC) before surgery, with less convincing data reported before chemoradiotherapy (CRT). MATERIAL AND METHODS: All patients with a locally advanced EC who had been treated with upfront CRT, between 2010 and 2015, were included. The decision of surgery was made after CRT (40-50 Gy). Muscle mass was measured on a single third lumbar vertebra CT-scan slice. Sarcopenia was internationally defined as skeletal muscle index of ≤39cm2/m2 for women and ≤55cm2/m2 for men. Results were additionally analyzed according to clinical parameters, with a cut-off based on the mean skeletal muscle lumbar index (SMI) of the population studied. RESULTS: Overall, 104 patients were included (male: 69%). Mean SMI was 35cm2/m2 for women and 46cm2/m2 for men, with 81% of patients being sarcopenic (n = 84). The 3-year overall survival (OS) rate, of 34.6%, was not significantly associated with sarcopenia in the whole population. In men, there was, however, a highly significant correlation between SMI and OS (p = 0.003), which remained significant upon multivariate analysis (p = 0.02). When using the mean SMI as cut-off, sarcopenia was significantly associated with 3-year OS (43.3% vs. 26.2%, p = 0.02). CONCLUSION: A high sarcopenia level appears negatively associated with OS in male EC patients treated with upfront CRT.

Multimodal strategy for the management of sphenoid osteoradionecrosis: Preliminary results.

OBJECTIVE: Osteoradionecrosis (ORN) of the sphenoid is a rare but potentially lethal complication that can occur after irradiation of nasopharyngeal and clival malignancies. The objective of this study was to describe a multimodal treatment strategy tailored to the clinical signs and to the radiological extent of the disease, and to report on its preliminary results. METHODS: Retrospective monocentric study at a tertiary skull base center. Patients treated for a sphenoid ORN from January 2014 to August 2018 were identified and charts were retrospectively reviewed for demographics, histologic tumor type, previous treatments of the tumor, clinical signs at presentation, radiological data, treatment, and outcomes. Sphenoid ORN was treated by a combination of medical therapy, endovascular treatment, and/or surgery. The use of each of these therapeutic modalities was based on the extent of ORN and on the presenting signs. RESULTS: Seven patients were included: four patients underwent endovascular treatment with occlusion of the internal carotid artery, five patients underwent surgical debridement, and covering of the exposed bone by a local flap, seven patients received antibiotics (in combination with pentoxyphilline, tocopherol, and clodronate in one case). Three patients died after progression of the ORN. The global survival rate was 57% (4/7) with a mean follow-up of 24 months. In one case, ORN was treated successfully by medical treatment only, with a combination of antibiotics, pentoxyphilline, tocopherol, and clodronate. CONCLUSION: This retrospective study describes the results of a management strategy adapted to the extent of the disease in sphenoid ORN and based on medical therapy only, or on a combination of medical therapy, interventional radiology, and/or surgery. LEVEL OF EVIDENCE: 4.

Urinary function and quality of life after radiotherapy for prostate cancer in patients with prior history of surgical treatment for benign prostatic hyperplasia.

BACKGROUND: To evaluate long-term IPSS score and urinary quality of life after radiotherapy for prostate cancer, in patients with prior history of surgical treatment for benign prostatic hyperplasia (BPH). METHODS: In this retrospective study, we reviewed medical records of patients treated in our department, between 2007 and 2013 with surgery for BPH followed by radiotherapy for localized prostate cancer. Patients were contacted to fill in IPSS questionnaire and they were also asked for urinary quality of life. Predictive factors known to be associated with bad urinary function were also analysed. RESULTS: Fifty-nine patients were included in our study. Median age was 70 years. Median follow-up was 4.6 years. Median radiotherapy dose was 78 Gy (5 × 2 Gy/week). Thirty patients (48.5%) received hormone therapy in combination with RT. Main surgery indications were urinary symptoms (65%) and urinary retention (20%). Five-year biochemical-disease free survival was 75% and 5-year clinical relapse free survival was 84%. At the time of the study, the IPSS after radiotherapy was as follows: 0-7: 77.6%; 8-19:20.7%; 20-35: 1.7%. Urinary quality of life was satisfactory for 74.2% of patients. After multivariate analysis, a high dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life (p = 0.04). CONCLUSION: External radiotherapy remains an appropriate treatment option without a major risk for deterioration in urinary function in patient with antecedent surgery for BPH. High dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life.

Plesiobrachytherapy for chest wall recurrences of breast cancer after mastectomy and radiotherapy for breast cancer.

PURPOSE: The purpose of the study was to evaluate the results of high-dose-rate plesiobrachytherapy for local relapse after mastectomy and radiotherapy in terms of both local control and survival. METHODS: We reviewed retrospectively 43 patients who experienced a chest wall relapse of breast cancer after local excision (22 patients) or not (21 patients). Patients were treated with an individually designed mold with four to six fractions of 3-6 Gy high-dose-rate brachytherapy, two fractions per week. Mean total dose was 24 Gy. RESULTS: After surgical resection, the 3- and 5-year local control rates were 80% and 73%, respectively. For nonresectable patients, the overall response rate was 86%, and the 3-year infield local control and chest wall local control were 51% and 26%, respectively. The 5-year survival rate was 50.5% for the whole population, 62% after surgery, and 45.4% for irresectable patients. Acute Grade 2 or 3 toxicity occurred in 43% of the patients, resolving in a few days. Two patients had a local necrosis lasting 3 to 7 months. Late toxicity was observed in 5 patients. CONCLUSIONS: High-dose-rate plesiobrachytherapy is a simple outpatient technique to treat chest wall local relapse of breast cancer. As a reirradiation technique, its tolerance is acceptable. This technique may obtain long-term local control after incomplete surgery; in case of nonresectable disease, a high response rate was observed, which might improve the quality of life of these patients.

Analyses of patterns-of-failure and prognostic factors according to radiation fields in early-stage Hodgkin lymphoma.

PURPOSE: Doses and volumes of radiation therapy (RT) for early stages of Hodgkin lymphoma (HL) have been reduced over the last 30 years. Combined modality therapy (CMT) is currently the standard treatment for most patients with early-stage HL. The aim of this study was to analyze the site of relapse after RT according to the extent of radiation fields. PATIENTS AND METHODS: Between 1987 and 2011, 427 patients were treated at our institution with RT ± chemotherapy for stage-I/II HL. Among these, 65 patients who experienced a relapse were retrospectively analyzed. Most patients had nodular sclerosis histology (86 %) and stage-II disease (75.9 %). Bulky disease was present in 21 % and 56 % of patients belonged to the unfavorable risk group according to European Organization for Research and Treatment of Cancer (EORTC)/The Lymphoma Study Association (LYSA) definitions. CMT was delivered to 91 % of patients. All patients received RT with doses ranging from 20 to 45 Gy (mean = 34 ± 5.3 Gy). The involved-field RT technique was used in 59 % of patients. RESULTS: The mean time between diagnosis and relapse was 4.2 years (range 0.3-24.5). Out-of-field relapses were suffered by 53 % of patients. Relapses occurred more frequently at out-of-field sites in patients with a favorable disease status, whereas in-field relapses were associated with bulky mediastinal disease. Relapses occurred later for favorable compared with the unfavorable risk group (3.5 vs. 2.9 years, p = 0.5). From multivariate analyses, neither RT dose nor RT field size were predictive for an in-field relapse (p = 0.25 and p = 0.8, respectively), only bulky disease was predictive (p = 0.018). CONCLUSION: In patients with bulky disease, RT dose and RT field size were not predictive for an in-field relapse. In this subgroup of patients, chemotherapy should be intensified. We confirmed the bad prognosis of early relapses.

10-Year follow-up of 621 patients treated using high-dose rate brachytherapy as ambulatory boost technique in conservative breast cancer treatment.

PURPOSE: Breast conserving treatment, consisting of lumpectomy followed by whole-breast irradiation, is considered the standard of care in early-stage breast cancer. Randomized studies have reported that delivering boost doses to tumor bed improves local control rates, particularly in young women. This study sought to evaluate local control and cosmetic results of delivering boost doses using a high-dose-rate (HDR) brachytherapy (HDRBT) in breast cancer conservative treatment. METHODS: We included 621 T1-T2, N0-N1 breast cancer patients who underwent lumpectomy, external irradiation (44Gy over 5weeks), and a boost dose of two fractions of 5Gy to the tumor bed by means of HDR iridium brachytherapy. Implantation was performed during the lumpectomy or 2-3weeks after external irradiation. Population characteristics were as follows: pTis=11.6%; pT1=63.4%; pT2=25.0%; median tumor size=1.5cm; histology: ductal carcinoma in situ (DCIS): 72 (11.6%); infiltrative ductal carcinoma (IDC): 471 (75.8%); other: 78 (12.6%). For IDCs, the surgical margins were positive in 38cases (6.2%) and an extensive intraductal component was present in 254 cases. RESULTS: With a median follow-up of 10.3years, 47 local relapses were observed (10-year local relapse rate: 7.4%). Small-volume implantation (V100<45cc) and ductal carcinoma in situ histology both significantly correlated with local relapse. The 10-year overall survival was 91%. Cosmetic results were evaluated in 264patients, proving excellent in 58 (22%), good in 153 (58%), fair in 40 (15%), and poor in 13 (5%). CONCLUSIONS: Small implant volume and ductal carcinoma in situ histology significantly correlated with local relapse following HDR brachytherapy dose boost in breast cancer conservative treatment. Modern image-guided breast brachytherapy techniques using surgical clips as a guide may decrease potential treatment targeting errors, consequently improving local control without increasing toxicity.

[Not Available]. / Jusqu'où aller dans la désescalade thérapeutique en radiothérapie du cancer du sein infiltrant ?

DE-ESCALATION OF RADIOTHERAPY OF INFILTRATING BREAST CANCER: WHERE CAN WE GO?: Adjuvant radiotherapy (RT) has an important role in the management of infiltrating breast cancer, not only to improve local control but also overall survival. So, all attempt of de-escalation must be performed in the context of large prospective studies. However, RT could induce some complications and last 5 to 7 weeks. Three ways of RT de-escalation have been studied.

Laparoscopic sleeve gastrectomy versus laparoscopic mini gastric bypass: One year outcomes.

PURPOSE: Sleeve gastrectomy (LSG) and mini gastric bypass (LMGB) was considered as emerging procedures but are now considered for many authors as an alternative of the Roux-Y gastric bypass because of similar percentages of weight loss and better postoperative morbidity profiles. However, studies comparing LSG and LMGB are scarce. MATERIALS AND METHODS: From January 2010 to July 2014, 262 and 161 patients underwent LSG or LMGB in two centre of bariatric surgery, respectively. At one year, rate of follow-up was 88.4%. Main outcome was % of Total Weight Loss (%TWL) at one year. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. RESULTS: After matching LSG (N = 136) and LMGB (N = 136) groups did not differ for initial BMI (kg/m(2)) (43.4 ± 6.5 vs. 42.8 ± 5.0; P = 0.34), % of female patients (91.9% vs. 93.4%; P = 0.64), age (years) (41.2 ± 12.3 vs. 41.2 ± 11.3; P = 0.99) and diabetes (15.4% vs. 19.9%; P = 0.34). At one year, %TWL, change in BMI and rate of stenosis were higher for LMGB group, respectively: 38.2 ± 8.4 vs. 34.3 ± 8.4 (P < 0.0001); -16.5 ± 4.6 vs. -14.9 ± 4.4 (P = 0.005) and 16.9% vs. 0% (P < 0.0001). In multivariate analyses (ß coefficient), LMGB was a positive independent factor of %TWL (2.8; P = 0.008). CONCLUSION: LMGB seems to have better weight loss at one year compared to LSG with higher gastric complications. Further long term studies are needed.

Interaction of low dose of fish oil and glucocorticoids on insulin sensitivity and lipolysis in healthy humans: A randomized controlled study.

SCOPE: This study examined the interaction of fish oil (FO) with dexamethasone on glucose and lipid metabolisms in healthy subjects. METHODS AND RESULTS: The study included two consecutive parts. Part A (randomized) in 16 subjects studied the effects of dexamethasone (2 days, 2 mg/day) versus placebo (lactose), part B (two parallel subgroups of eight) studied the interaction of FO (3 wk, 840 mg/day of EPA + DHA) with dexamethasone. Insulin sensitivity of lipolysis (d5-glycerol infusion + microdialysis), endogenous glucose production, and muscle glucose uptake were assessed by a three-step hot insulin clamp and substrate oxidation by indirect calorimetry. Dexamethasone induced liver and peripheral insulin resistance, an increase in fat oxidation, and a decrease in suppression of plasma nonesterified fatty acids (NEFAs). FO amplified the effects of dexamethasone by increasing liver and muscle insulin resistance, by reducing suppression of plasma NEFAs and fat oxidation and by increasing adipose tissue (AT) lipolysis. CONCLUSION: FO, given at a moderate dose in healthy subjects prior to a very short-term (2 days) low dose of a synthetic glucocorticoid, worsened its deleterious effects on insulin sensitivity. The enhancing effect of FO on fat oxidation and AT lipolysis might be a protective effect toward an increase in fat mass.

Efficacy and safety of vinorelbine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma patients.

The aim of this study was to evaluate the efficacy and tolerance of vinorelbine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral or intravenous vinorelbine according to the pluridisciplinary tumor board's decision. Efficacy and safety outcomes were analyzed retrospectively. Twenty-three patients were included in the study. Sixteen patients (69%) had received at least two previous lines of chemotherapy. The disease control rate was 19%. The median progression-free survival was 2.6 months and the median overall survival was 3.4 months. The rate of grade 3-4 side effects was low (13%). Only one patient discontinued treatment because of side effects. Vinorelbine seems to be a well-tolerated regimen in heavily pretreated patients. However, this regimen does not seem to be efficient enough to be recommended.

Neoadjuvant or adjuvant therapy for gastric cancer.

Currently, there is no international consensus on the best treatment regimen for patients with advanced resectable gastric carcinoma. In the United States, where a limited lymph-node dissection is frequently performed, adjuvant chemoradiotherapy after surgery is the standard treatment. In Europe, intensified perioperative chemotherapy is commonly administered. In Japan and South Korea, postoperative S-1-based adjuvant chemotherapy after surgery with D2 lymph-node dissection is the standard treatment. Several ongoing trials are currently evaluating the optimal sequence of chemotherapy, radiotherapy, and surgery, as well as the place of targeted therapeutic agents in the treatment of advanced gastric carcinoma.

Fish oil attenuates adrenergic overactivity without altering glucose metabolism during an oral glucose load in haemodialysis patients.

Haemodialysis patients display an increased cardiac mortality, which may be partly related to increased sympathoadrenal activity and insulin resistance. Fish oil decreases adrenal activation induced by mental stress and has an insulin sensitizing effect in healthy subjects. Whole-body glucose metabolism after oral glucose was studied in eight haemodialysis patients before and after a 3-week oral fish oil supplementation (i.e. EPA + DHA at 1.8 g/d). Plasma glucose fluxes were traced by using [6,6- (2)H2]glucose infusion. Substrate oxidation was determined by using indirect calorimetry. Each patient was studied in the basal state and over the 6 h following absorption of a 1 g/kg glucose load. Energy expenditure in response to glucose re-increased over the last 2 h of the experiment (P < 0.05), which coincided with an increase in plasma catecholamines, especially epinephrine (P < 0.05), strongly suggesting a sympathoadrenal overactivity. Fish oil supplementation blunted both re-increase in thermogenic response and concomitant increase in plasma epinephrine, but not in plasma norepinephrine, over the last 2 h of the experiment. Fish oil did not alter either whole-body glucose metabolism or substrate oxidation. These data show that in haemodialysis patients, fish oil attenuates adrenal overactivity induced by oral glucose but does not modulate whole-body glucose metabolism and insulin sensitivity.