[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial.

BACKGROUND: To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN). PATIENTS AND METHODS: Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20. RESULTS: Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash. CONCLUSION: Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Histosurgical mapping of endoscopic endonasal surgery of sinonasal tumours to improve radiotherapy guidance.

PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

[Prognostic analysis of different comprehensive treatment models for locally advanced esophageal squamous cell carcinoma based on propensity score matching].

Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1∶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.

[Proposal for the delineation of postoperative primary clinical target volumes in ethmoid cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers de l'ethmoïde.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Split-course hypofractionated radiotherapy for aged and frail patients with head and neck cancers. A retrospective study of 75 cases.

PURPOSE: To assess the efficacy and the tolerance of a split course hypofractionated (SCH) radiotherapy (RT) protocol in head and neck cancer (HNC) for eldery and/or unfit patients (pts). PATIENTS AND METHODS: Pts with HNC treated by SCH-RT in two institutions were included retrospectively. The main SCH RT regimen was two courses of 30 grays (Gy)/10 fractions separated by 2-4 weeks, without any systemic therapy. RESULTS: Between February 2012 and January 2019, 75 consecutive patients were analyzed. The median age was 80 years (range: 45.7-98.2) and 53 (70.7%) were men. Sixty-one (81.3%) pts had stage III/IV disease and 54 (72%) had at least two comorbidities. All of them were treated with intensity-modulated radiotherapy. Median follow-up was 10.6 months (range: 3.1-58.3). Local control at 12 and 24 months was 72.8% IC95%[62-85.5] and 51.7% IC95%[38.1-70.1] respectively. Progression free survival (PFS) at 12 and 24 months were 47.7% IC95%[37.4-60.8] and 41% IC95%[15-36.4] respectively, with a median of 11.5 months IC95%[8.9-17]. OS at 12 and 24 months were 60.4% IC95%[50-73.1] and 41% IC95%[30.6-54.9] respectively, with a median of 19.3 months IC95%[11.9-25.8]. Acute and late grade 3 or higher toxicities occurred for 6 (8%) and 3 (4%) pts. CONCLUSION: The present SCH-RT regimen seems effective, well-tolerated and could represent an alternative to palliative strategies for pts deemed unfit for standard exclusive RT.

Radiation therapy on primary tumour of synchronous metastatic head and neck squamous cell carcinomas.

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.

[Complications of 2 133 cases of pediatric long bone fracture undergoing elastic stable intramedullary nailing in a single medical center].

Objective: To summarize the clinical data of elastic stable intramedullary nailing(ESIN) in the treatment of long bone fracture of children in a single medical center, and to analyze the problems occurred after the ESIN surgery and corresponding solutions. Methods: A retrospective analysis was conducted regarding the clinical data of 2 133 pediatric long bone fractures conforming to inclusion and exclusion criteria from June, 2005 to December, 2017 in Department of Orthopedics, Children's Hospital of Nanjing Medical University.There were 1 191 boys and 942 girls, aged from 23 months to 14 years with mean age of (5.7 ± 3.1)years.There were 1 866 cases treated with closed reduction with ESIN, while 267 cases were treated with small incision assisted reduction with ESIN.Postoperative problems have been statistically analyzed. Results: There were altogether 2 133 children, including 603 cases of femur, 311 cases of tibia, 8 cases of fibula, 219 cases of humerus, and 992 cases of ulna/radius.The postoperative complications mainly consist of 62 cases of needle tail irritation reaction, 21 cases of misalignments of fracture alignment, 11 cases of intramedullary nail deformity or angular deformity, 7 cases of limb shortening, 14 cases of limited joint activity, 4 cases of nerve injury, 2 cases of tendon injury, 14 cases of difficult nail removal, 4 cases of cortical cleavage, 8 cases of delayed union, 1 case of nonunion, 6 cases of varus/valgus deformity, 5 cases of epiphyseal injury, 6 cases of ESIN exposure, and 2 cases of metal debris of ESIN' end. Conclusions: The complications of treatment for children with long bone fractures by ESIN cannot be ignored.To master the important biomechanical properties, to get familiar with the local anatomy and to avoid obvious technical errors can reduce the occurrence of postoperative complications.

[Effects of Src on cervical cancer cells proliferation and apoptosis through ERK signal transduction pathway].

Objective: To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway. Methods: Experimental study was carried out in vitro. Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2. Then, the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM). Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2, c-Fos and c-Jun mRNA and protein respectively. The database was established and analyzed with SPSS statistical software (version 20.0). Results: After down-regulating Src, the cell proliferation was inhibited and cell apoptosis was induced. The proportions of G0/G1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased. Meanwhile, the mRNA levels of ERK 1, ERK 2, c-Fos and c-Jun increased. And the expression levels of ERK 1/2, phosphorylated ERK 1/2 (p-ERK 1/2) and phosphorylated c-Fos (p-c-Fos) protein decreased, while c-Jun and phosphorylated c-Jun (p-c-Jun) protein expression increased. In addtion, the change level of Hela cell, p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition. Conclusions: Src, involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos, might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis. The infection with HPV might have adjustable effect on this process.

[Effect of extracellular signal-regulated kinas 1/2 expression and HPV16 infection and their interaction in progression of cervical cancerization].

Objective: To investigate the effect of ERK1/2 protein expression and HPV16 infection, as well as their interaction in the cervical carcinogenesis. Methods: A total of 176 patients, including 34 cases with normal cervix (NC), 26 cases with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ), 57 cases with cervical intraepithelial neoplasm Ⅱ/Ⅲ (CIN Ⅱ/Ⅲ) and 59 cases with cervical squamous cell carcinoma (SCC), were enrolled from Shanxi Tumor Hospital, Shanxi Maternal and Child Health Center, Jincheng Coal General Hospital from September 2013 to March 2014. The information about their demographic characteristics and risk factors associated with cervical cancer was collected with structural questionnaire, and cervical tissue samples were collected from each subject. HPV16 infection was detected by PCR, and phosphorylation of ERK1/2 (p-ERK1/2) protein expression levels were detected by immunohistochemistry. Meanwhile, cervical cancer cell lines Siha (HPV16 positive) and C33A (HPV negative) were treated with ERK inhibitor U0126 in vitro. Cell proliferation was determined by living cell count, cell cycle and apoptosis was detected by flow cytometry. Results: The HPV16 infection rate (trend χ(2)=17.99, P<0.001) and p-ERK1/2 protein high expression (trend χ(2)=10.58, P=0.001) increased gradually along with the severity of cervix lesions. There was an additive interaction between HPV16 infection and p-ERK protein expression in the CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups. Cell experiments showed that after ERK inhibition, the proliferation of the two cells were reduced (Siha: t=6.863, P<0.001; C33A: t=7.092, P<0.001) and the apoptosis were increased (Siha: t=-5.201, P=0.006; C33A: t=-4.335, P=0.005). After ERK inhibition, the cell proliferation index of Siha (HPV16 positive) was higher than that of C33A (HPV16 negative) (t =7.066, P<0.001), but the apoptosis rate of Siha was lower than that of C33A (t=-2.431, P=0.057). Conclusions: HPV16 infection and the high expression of p-ERK1/2 could increase the risk of cervical cancer. And there might be synergistic actions between the two factors in the progression of cervical cancer. The effect of ERK1/2 activation to HPV16 infection cells might be more significant in the process of cervical cancer cell proliferation and apoptosis.

Implementation of intensity-modulated radiotherapy for head and neck cancers in routine practice.

PURPOSE: To report on patterns of relapse following implementation of intensity-modulated radiotherapy and subsequent changes in practice in a tertiary care centre. PATIENTS AND METHODS: Between 2008 and 2011, 188 consecutive patients (mean age 59 years old) received intensity-modulated radiotherapies with curative intent for squamous cell carcinomas of the oral cavity (17.5%), oropharynx (43%), hypopharynx (21%), larynx (14%), sinonasal cavities (6%), nasopharynx (1.5%) at the university hospital of Besançon. There were stage I and II 9%, III 24.5%, IV 66.5%. One hundred and thirty-eight underwent exclusive intensity-modulated radiotherapy, 50 underwent postoperative intensity-modulated radiotherapy, 174 had concurrent chemotherapy, 57 had induction chemotherapy. Dynamic intensity-modulated radiotherapy with static fields was performed for all patients using sequential irradiation in 174 patients and simultaneous integrated boost irradiation in 14 patients. RESULTS: With a median follow-up was 27.5 months, there was 79% of locoregional failures occurred in the 95% isodose. Two-year overall survival, disease-free, local failure-free and locoregional failure-free survival rates were73%, 60%, 79% and 72%, respectively. Prognostic factors for disease-free survival were stage (IV vs. I-III) with a relative risk of 1.7 [1.1-2.8] (P=0.02) and T stage with 1.6 [1.04-2.5] (P=0.03). CONCLUSION: The current series showed similar patterns of failure as in other tertiary care centres. We did not identify intensity-modulated radiotherapy specific relapse risks.

[Follicular dendritic cell sarcoma in head and neck region]. / Sarcome à cellules folliculaires dendritiques de la région ORL.

Follicular dendritic cell sarcomas are a recently described entity, with biphenotypic characteristics of lymphomas and sarcomas. The treatment is hardly consensual in the literature. We report two head and neck cases, of favorable outcome after surgery and radiotherapy. Histopathology and differential diagnoses are discussed as well as the therapeutic strategies used.

[Target volumes in cervical lympadenopathies of unknown primary: toward a selective customized approach? On behalf of REFCOR]. / Volumes cibles en radiothérapie des adénopathies cervicales de primitif inconnu : état des lieux et pistes vers une approche sélective raisonnée sous l'égide du Refcor (Réseau d'expertise français des cancers ORL rares).

The treatment of carcinomas of unknown primary revealed by cervical lymphadenopathy is based on neck dissection and nodal and pan-mucosal irradiation to control the neck and avoid the emergence of a metachronous primary. The aim of this review was to assess diagnostic and therapeutic approaches and criteria that may be used for a customized selective approach to avoid severe toxicities of pan-mucosal irradiation. A literature search was performed with the following keywords: cervical lymphadenopathy, unknown primary, upper aerodigestive tract, cancer, radiotherapy, squamous cell carcinoma, variants. The diagnostic workup includes a head and neck scanner or MRI, ((18)F)-FDG PET CT, a panendoscopy and tonsillectomy. Squamous cell carcinoma represents over two thirds of cases. The number of metastatic cervical nodes, nodal level, and histological variant (associated with HPV/EBV status) may determine the primary site origin and might be weighted for the determination of radiation target volumes on a multidisciplinary basis. A selective customized approach is relevant to decrease radiation toxicity only if neck and mucosal control is not impaired. Although no recommendation can yet be made in the absence of sufficient level of evidence, the relevance of systematic pan-mucosal irradiation appears questionable in a number of clinical situations. Accordingly, a customized selective redefinition of target volumes may be discussed and be prospectively evaluated in relation to the therapeutic index obtained.

[Radiation therapy in thyroid cancer]. / Place de la radiothérapie externe dans les cancers de la thyroïde.

Anaplastic thyroid cancers represent 1-2% of all thyroid tumours and are of very poor prognosis even with multimodality treatment including external beam radiation therapy. Conversely, differentiated thyroid carcinomas (at least 80% of thyroid cancers) hamper good prognosis with surgery with or without radioiodine and there is hardly any room for external beam radiation therapy. Insular and medullar carcinomas have intermediary prognosis and are rarely irradiated. We aimed to update recommendations for external beam irradiation in these different clinical situations and put in light the benefits of new irradiations techniques. A search of the French and English literature was performed using the following keywords: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy, surgery, histology and prognostic. Non-mutilating surgery (often limited to debulking) followed by systematic external beam radiation therapy is the standard of care in anaplastic thyroid cancers (hyperfractionated-accelerated radiation therapy with low-dose weekly doxorubicin with or without cisplatin if possible). Given anaplastic thyroid cancers' median survival of 10 months or less, neoadjuvant and adjuvant chemotherapy may also be discussed. Ten-year survival rates for patients with papillary, follicular and Hürthle-cell carcinomas are 93%, 85%, and 76%, respectively. Massive primary incompletely resected iodine-negative disease indicates external beam radiation therapy. Older age (45 or 60-year-old), poor-prognosis histological variants (including tall cell cancers) and insular cancers are increasingly reported as criteria for external beam radiation therapy. Massive extracapsular incompletely resected nodal medullary disease suggests external beam radiation therapy. Radiation therapy morbidity has been an important limitation. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumour coverage and organ sparing, reducing late toxicities to less than 5%. The role of radiation therapy is evolving for anaplastic thyroid cancers using multimodal strategies and new chemotherapy molecules, and for differentiated cancers using minor criteria, such as histological variants, with IMRT becoming a standard of care.

Indications of external beam radiation therapy in non-anaplastic thyroid cancer and impact of innovative radiation techniques.

BACKGROUND: The mainstay of treatment for differentiated thyroid carcinomas is surgery. There is hardly any room for radiation therapy in differentiated thyroid carcinomas. We aimed to update recommendations for RT in the context of histological variants, increased use of radioiodine and new irradiations techniques. MATERIALS AND METHODS: A search of the French and English literature was performed using thyroid carcinoma, radiation therapy, surgery, variants and radioiodine. RESULTS: Papillary, follicular, Hürthle and medullary carcinomas represent about 80%, 11%, 3% and 4% of all thyroid carcinomas, respectively. Ten-year survival rates for patients with papillary, follicular and Hürthle cell carcinomas are 93%, 85%, and 76%, respectively. The occurrence of criteria such as older age (45 or 60 years-old), massive primary disease, extensive extracapsular spread and macroscopic iodine-negative components inconsistently indicate external beam irradiation (EBRT). The impact of EBRT on poorer-prognosis histological variants is an emerging issue. Noteworthy, the incidence of laryngeal and wound healing complications has been an important limitation to EBRT. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumor coverage and organ sparing such as the larynx, thus reducing late toxicities to less than 5%. Iodine contrast agents should be avoided during 4-6 weeks before radioiodine. PET CT is increasingly used in iodine-negative tumors. CONCLUSION: There are elective indications for EBRT and IMRT has the potential to improve local control.

Chemoradiation in anaplastic thyroid carcinomas.

BACKGROUND: ATC represents 1-2% of all thyroid carcinomas. Median survival is poor (3-10 months). Our goal is to update recommendations for RT in the context of new irradiation techniques. MATERIALS AND METHODS: A search of the French and English literature was performed with terms: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy and surgery. Level-based evidence remains limited in the absence of prospective studies and the small size of retrospective series of this rare tumor. RESULTS: Surgery when possible should be as complete as possible but without mutilation given the 8-month median survival of ATC. It should be followed by systematic chemoradiation in ATC. Initiation of treatment is an emergency given fast tumor doubling time. The most promising results of chemoradiation to date have been shown in series of radiation therapy (+/- acceleration) combined with doxorubicin +/- taxanes or cisplatin. Adjuvant chemotherapy (doxorubicin, cisplatine and/or taxane-based) may also be recommended given the metastatic potential of ATC and warrants further investigations. Data on neoadjuvant chemotherapy are missing. Intensity modulated radiation therapy offers clear dosimetric advantages and has the potential to improve tumor and nodal (posterior neck, mediastinum) coverage, i.e., locoregional control while optimally sparing the spinal cord, larynx, parotids, trachea and esophagus. PET-CT and MRI may be used for RT planning. CONCLUSION: Chemoradiation with debulking surgery whenever possible is the mainstay of treatment of anaplastic thyroid carcinomas (ATC). EBRT using IMRT has the potential to improve local control. Taxane-doxorubicin concomitant chemoradiotherapy is worth further investigation.

Thermal properties of ration components as affected by moisture content and water activity during freezing.

Beef roast with vegetables is an example of a meal, ready-to-eat (MRE) ration entrée. It is a mixture of meat, potato, mushroom, and carrot with a gravy sauce. The thermal properties of each component were characterized in terms of freezing point, latent heat, freezable and unfreezable water contents, and enthalpy during freezing using differential scanning calorimetry. Freezing and thawing curves and the effect of freezing and thawing cycles on thermal properties were also evaluated. The freezing points of beef, potato, mushroom, and sauce were all in the range of -5.1 to -5.6 degrees C, but moisture content, water activity, latent heat, freezable and unfreezable water contents, and enthalpy varied among these components. Freezing temperature greatly affected the unfrozen water fraction. The unfreezable water content (unfrozen water fraction at -50 degrees C) of ration components was in the range of 8.2% to 9.7%. The freezing and thawing curves of vegetables with sauce differed from those of beef but took similar time to freeze or thaw. Freezing and thawing cycles did not greatly affect the thermal properties of each component. Freezing point and latent heat were reduced by decreasing moisture content and water activity of each component. Water activity was proportionally linear to freezing point at a(w) > 0.88, and moisture content was proportionally linear to freezable water content in all ration components. Water was not available for freezing when moisture content was reduced to 28.8% or less. This study indicates that moisture content and water activity are critical factors affecting thermal behavior of ration components during freezing.

Effect of oxygen content on the transport properties of LaTiO(3+ß/2) thin films.

The structural and transport properties of LaTiO(3+ß/2) epitaxial thin films, grown at different oxygen pressures ranging from 6.6 × 10(-4) to 5 Pa, have been investigated. X-ray diffraction peaks of the films shift to lower angles with increasing oxygen pressure, indicative of a variation of the corresponding lattice spacing. All the films show T(2) dependence of resistivity over a large temperature range of ∼200 K, suggesting a band-filling-induced metallic Fermi-liquid behaviour. Upturns in resistivity have been revealed at low temperatures, which could be ascribed to the Anderson-localization effect caused by the cation vacancies. Furthermore, for the thin films grown at high oxygen pressures of 0.5 and 5 Pa, the dependence of resistivity on temperature shows a maximum at high temperatures. The maximum seems to support the argument that transition between t-orbital ordering and disordering plays an important role in dominating transport properties at high temperatures. Carrier density deduced from Hall coefficient increases with the decrease of oxygen content, and shows strong temperature dependence. From the experimental data, it can be asserted that in the LaTiO(3+ß/2) thin films, besides the band filling effect, localization or disorder caused by La and Ti vacancy effects controls the unique transport properties.

Effects of pregnant mare serum gonadotropin (eCG) on follicle development and granulosa-cell apoptosis in the pig.

The effect of eCG on follicular development and granulosa-cell apoptosis in sexually mature and immature gilts and on granulosa-cell apoptosis in vitro were studied. The sexually mature gilts were treated with eCG on Day 11 of the estrous cycle, and effects were analyzed at different times after treatment with untreated animals at corresponding stages of the cycle as controls. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), hematoxylin and eosin staining, and DNA ladder. The proportion of apoptotic cells in atretic follicles (39%) was significantly higher (P<0.01) than that in healthy follicles (9%). At 24h after eCG treatment in mature gilts, the total number of follicles visible on the ovarian surface (57 per ovary), the number of small (<3mm) follicles (31.5 per ovary) and the number of medium-sized (3-5mm) follicles (23 per ovary) were significantly higher (P<0.05) than those of control animals (28, 20 and 6.5 per ovary, respectively), and declined gradually thereafter to below the level of control animals. The number of large (>or=5mm) follicles began to show a marked increase at 72h after eCG (8.5 versus 2.5, P<0.05). At 24h after eCG treatment, the proportions of apoptotic cells in small (7.2%) and medium-sized follicles (7.4%) were markedly lower (P<0.01) than those in controls (21.5 and 21%, respectively) and increased gradually thereafter to approach the level in controls. The percentage of apoptotic cells in large follicles (10% at 24h post-eCG) did not change significantly. Before eCG treatment, there were markedly fewer follicles of all types on ovaries of immature gilts than of mature gilts (9 versus 25 per ovary) and the proportion of apoptotic cells in small and medium follicles was high (25 and 34%, respectively). After eCG treatment, the changes in follicle number and proportion of apoptotic cells in the immature gilts followed a similar pattern to that of the mature gilts. Equine chorion gonadotropin inhibited apoptosis of granulosa cells cultured either in vitro or in intact follicles in a dose-dependent manner. Thus, follicular atresia in the pig, as in other animals, was characterized by apoptosis of large numbers of granulosa cells, and eCG promoted follicular development by inhibition of granulosa-cell apoptosis.