Quality of weight loss during chemoradioherapy in patients with nasopharyngeal cancers.

PURPOSE: Radiation therapy with chemotherapy (CCR) is currently the gold standard treatment for nasopharyngeal carcinoma (NPC). Anatomical changes are mainly due to weight loss. Our prospective study aimed to evaluate the nutritional status and the quality of weight loss in our patients to adapt the subsequent nutritional management of patients during treatment for NPC. PATIENTS AND METHODS: A prospective, single-center study of 27 patients with non-metastatic NPC treated in our oncology radiotherapy department between August 2020 and March 2021. Data from interrogation, physical examination, and bioelectrical impedancemetry (weight [W], body mass index [BMI], fat index [GI], fat mass [FM], and fat-free mass (FFM]) were collected at the beginning, the mid, and the end of treatment. RESULTS: Weight loss from mid to end of treatment (median=-4kg [-9.4; -0.9]) was greater than that from baseline to mid-treatment (median=-2.9kg [-8.8; 1.8]) (P=0.016). Weight loss during the entire treatment was -6.2kg [-15.6; -2.5] (8.4%). The losses of FM were identical between the beginning-mid treatment and the mid-end treatment; they were respectively -1.4kg [-8.5; 4.2] and -1.4kg [-8.2; 7.8] (P=0.4). FFM losses between the mid- and the end of treatment (-2.5kg [-27.8; 0.5]) were greater than those between baseline and mid-treatment (-1.1kg [-7.1; 4.7]) (P=0.014). Median FFM loss during treatment was -3.6kg [-28.1; 2.6]). CONCLUSION: The results of our study show that weight loss during CCR for NPC is complex and is not just about loss but about a disruption of body composition. Regular follow-ups by nutritionists are required to prevent denutrition during treatment.

[Pre- and post-chemotherapy tumor volumes: New prognostic factors in nasopharyngeal carcinoma]. / Volumes tumoraux avant et après chimiothérapie : de nouveaux facteurs pronostiques dans les carcinomes nasopharyngés.

PURPOSE: The pre- and post-induction chemotherapy tumor volumes of nasopharyngeal carcinomas may be prognostic indicators for adapting the therapeutic strategy. The objective of our study is to assess the prognostic impact of pre- and post-induction chemotherapy volumes in patients treated for locally advanced nasopharyngeal carcinomas. PATIENTS AND METHODS: This is a retrospective study including 52 patients with locally advanced nasopharyngeal carcinoma treated with 3 courses of induction chemotherapy (TPF) followed by intensity modulated radiotherapy associated with concomitant chemotherapy. RESULTS: The median initial and post induction chemotherapy total volumes were 92.3 and 41.5mL, respectively. At 3 years, the LRFS, DMFS, DFS and OS were respectively 85.9%, 63.5%, 56.8% and 67.8%. In multivariate study, the combination of a high initial volume (>100mL) and post-chemotherapy volume (>35mL) was an independent factor for LRFS, DMFS, DFS and OS. The total baseline volume had a better predictive prognostic value for DFS and OS than the TNM classification (8th edition 2017). CONCLUSION: The prognostic weight of tumor and nodal volumes was greater than the TNM classification (8th edition). The pre- and post-chemotherapy tumor volumes allow selecting a high-risk patients' subgroup "high initial and post chemotherapy volumes" in which it would be advisable to offer more intensive treatment regimens.

[Current management and perspectives for locally advanced nasopharyngeal carcinoma]. / État des lieux et perspectives thérapeutiques pour les carcinomes nasopharyngés localement évolués.

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures.

[What is the impact of IMRT of nasopharyngeal carcinomas on glandular structures?] / Quel impact de la RCMI des carcinomes nasopharyngés sur les structures glandulaires ?

PURPOSE: The aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts. PATIENTS AND METHODS: Twenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary). RESULTS: We observed a decrease in the volume of right and left parotids (-27.9% and -27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was -36.1% on the right and -27.28% on the left. The value of reduction of the thyroid gland was -18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid. CONCLUSION: The modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy.

[Contribution and limits of intensity-modulated reirradiation of nasopharyngeal carcinomas]. / Apports et limites de la réirradiation conformationnelle avec modulation d'intensité des carcinomes nasopharyngés.

PURPOSE: We report in this study, the dosimetric and carcinologic results of intensity-modulated technique for the reirradiation of nasopharyngeal carcinomas. PATIENTS AND METHODS: Eight patients reirradiated with intensity-modulation technique between January 2015 and December 2017 were included. We noted for each patient: the minimum, maximum and average doses, the dose received by 95% (D95%), 98% (D98%) and 2% (D2%) of the volume to be irradiated, the homogeneity and conformity indices and doses to the organs at risk. RESULTS: Target volume coverage was satisfactory with a median of D95% greater than 57Gy (95% of the prescribed dose). The median maximum dose received by the spinal cord and brainstem were 8.2Gy and 18.25Gy, respectively. After a median follow-up of 14.5 months [1-29 months], five patients were in complete remission of their disease. Overall survival at 2 years was 66.7%. An increase in preexisting late toxicity after the first irradiation (now grade 2 or above) was found in four patients (50% of cases). CONCLUSION: Intensity-modulation is an attractive technique for reirradiation of the nasopharynx. It allows a better conformity of the dose to the target and a reduction of the doses on the already irradiated critical organs. This offers good control of the disease with fewer severe late toxicities.

[Local failures of nasopharynx carcinoma: Anatomoclinical aspects and therapeutic results]. / Aspects anatomocliniques et thérapeutiques des récidives locales des carcinomes du nasopharynx.

PURPOSE: Retrospective analysis of clinical aspects and therapeutic results of nasopharynx cancer local failures. PATIENTS AND METHODS: Forty patients with local failure with or without nodal involvement of nasopharyngeal carcinoma were treated between 1993 and 2013. Reirradiation of nasopharynx was delivered at the dose of 60Gy. Platinum-based chemotherapy was indicated in case of locally advanced disease and/or associated nodal failure. RESULTS: The mean age at diagnosis of primitive tumour was 41.9 years (26-67 years). The mean time of relapse occurrence was 31.7 months (6-104 months). Sixty five percent of failures were confined to the nasopharynx. Nodal failure was seen in 14 cases. Twenty-eight patients had chemotherapy. Twenty-five patients had reirradiation of nasopharynx. Mean follow-up was 98 months (12-191 months). Fourteen patients were still alive and in complete remission. Five-year survival was 40.7%. Xerostomia was the most frequent late toxicity. No haemorrhage was seen. CONCLUSION: Reirradiation is the mainstay treatment of nasopharyngeal local failure. Late toxicity seems to decrease with novel techniques of reirradiation.

[Large cell neuroendocrine carcinoma of the nasopharynx: A case report]. / Tumeur neuroendocrine à grandes cellules du nasopharynx : à propos d'un cas.

Neuroendocrine carcinoma of the head and neck is a rare entity. The parotid gland is the most commonly affected site. A nasopharyngeal site has not been previously described. We report a 35-year-old patient who consulted for tinnitus and nasal obstruction. The assessment found a nasopharyngeal tumour T4N0M0. The patient underwent 6 cycles of chemotherapy based on VP16 and cisplatin, followed by radiotherapy at a dose of 70 Gy to the nasopharynx and 50 Gy to the neck. The evolution was marked by clinical improvement and radiological stability. Six months after the end of treatment, the patient had a local and meningeal relapse. He received palliative care. He died 19 months after the end of treatment.

[Is there any difference in therapeutic results of nasopharyngeal carcinoma between adults and children?]. / Résultats thérapeutiques du cancer du cavum: y a-t-il une différence entre enfants et adultes?

PURPOSE: To compare therapeutic results of nasopharyngeal carcinoma between adults and children. PATIENTS AND METHODS: Three hundred and seventy seven patients with nasopharyngeal carcinoma received a radiotherapy between 1993 and 2007. Sixty-nine of them were 20years old or less. Two hundred and sixty eight patients received a chemotherapy (neoadjuvant or concomitant). RESULTS: Overall survival and disease-free survival at 5 years were 67 % and 59.4 % in all patients, respectively. Overall survival rates at 5 years in children and adults were 66 % and 64 %, respectively (P=0.17), disease-free survival rates at 5 years were 66 % and 57 %, respectively (P=0.17). Local failures occurred more frequently in adults than in children (1.4 % versus 14 %). However, metastatic events were frequently seen in children. Late toxicities were important in children, xerostomia was the most common one. CONCLUSION: Despite locally advanced disease in children, therapeutic results were better than in adults but not statistically significant. The use of treatment combination (chemotherapy and radiotherapy) in juvenile nasopharyngeal carcinoma may explain our findings.

Thyroid toxicity after radiotherapy of nasopharyngeal carcinoma.

OBJECTIVES: To analyze retrospectively the risk factors for occurrence of thyroid toxicity after radiotherapy for nasopharyngeal cancer and to demonstrate the necessity of a long-term post-therapeutic screening. PATIENTS AND METHODS: Between 1993 and 2004, 239 patients with non-metastatic nasopharyngeal carcinoma were treated by conventional radiotherapy with or without chemotherapy. Radiotherapy was delivered by a standard fractionation (2 Gy/fraction, 5 fractions/week) for 157 patients and hyperfractionation (1.6 Gy/fraction, 2 fractions/day, 5 days/week) for 82 patients. An evaluation of thyroid late toxicity was performed according to tumor stage, age, gender, time after treatment, irradiation method and association or not with chemotherapy. RESULTS: After a median follow up of 111 months, 72 patients (30%) had primitive and/or pituitary thyroid dysfunction. Fifty-seven patients (24%) experienced hypothyroidism, peripheral in 92% of cases (biological 73%, clinical 19%) and central in 8% of cases. Hypothyroidism was detected at a mean 37 months follow up. All patients received replacement treatment with l-thyroxin. The actuarial rate of hypothyroidism was 18.1%, 24.3% and 35% at respectively 3, 5 and 10 years. Only female gender was found as a risk factor for occurrence of hypothyroidism in univariate analysis. However, younger age and advanced tumor stage were associated with a higher risk but the difference was not significant (P = 0.08 for each). There was no difference for other factors: nodal stage, modality of radiation and chemotherapy treatment. The multivariate analysis did not show any risk factor. CONCLUSION: Thyroid dysfunction after radiotherapy for nasopharyngeal carcinoma is frequent and requires systematic screening to begin adequate treatment earlier. Only gender has been identified as risk factor in univariate analysis in this study.

[Juvenile nasopharyngeal carcinoma: anatomoclinic, biologic, therapeutic and evolutive aspects]. / Les cancers du cavum juvéniles: aspects anatomocliniques, biologiques, thérapeutiques et évolutifs.

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult's NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochemical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult's NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.

[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance]. / Le carcinome nasopharyngé en Afrique du Nord et dans le Sud-Est asiatique: entre similitude et différence.

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

[Late neurotoxicity after nasopharyngeal carcinoma treatment]. / Toxicité neurologique tardive après traitement des carcinomes nasopharyngés.

PURPOSE: A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy. PATIENTS AND METHODS: Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity. RESULTS: After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p=0.02). On multivariate analysis, hyperfractionation and age were insignificant. CONCLUSION: Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study.

[Head and neck sarcoma]. / Les sarcomes de la tête et du cou.

INTRODUCTION: Head and neck sarcomas comprise a heterogeneous and biologically diverse set of rare neoplasms. The difficulty treating the disease requires multidisciplinary consultation to improve outcome. In an effort to clarify the clinical behavior of head and neck sarcomas and evaluate treatment, we present our experience and review the relevant literature. PATIENTS AND METHODS: This is a retrospective analysis of 15 patients with histologically proven head and neck sarcoma treated in the ENT department between 1998 and 2007. All cases were confirmed by histologic exam with immunohistochemical analysis. RESULTS: Nine women and six men were included in the study. The mean age was 38.4 years (range: 6-73 years). Computed tomography and MRI were done in 66.7% and 60% of the patients, respectively, to evaluate tumor extension. Metastases were demonstrated in three cases. Curative treatment in eight cases was based on different combinations of chemotherapy, radiotherapy, and surgery. Complete remission was obtained in eight cases. Local recurrence was noted in two cases. Two patients died from tumor metastasis. Two patients were lost to follow-up. CONCLUSION: Head and neck sarcomas present diverse rare neoplasms. They make up 5%-20% of all soft tissue sarcomas. All age groups can be affected by this neoplasm, with no predominance in one sex or the other. The most common histologic type is rhabdomyosarcoma, especially in children. Because of the potential for systemic metastasis, extension must be assessed. Treatment is based essentially on the association of surgery, radiotherapy, and chemotherapy to optimize therapeutic results. Five-year survival varies between 44% and 80%.

[Hypothyroidism following cervical irradiation in the management of carcinoma of the nasopharynx and of the breast: a prospective study on eighty-four cases]. / Hypothyroïdie après irradiation cervicale dans le traitement des cancers du nasopharynx et du sein: étude prospective à propos de 84 patients.

PURPOSE: 1/ To evaluate the incidence of hypothyroidism following radiotherapy in the management of breast and nasopharyngeal carcinomas, 2/ to define the role of a systematic post therapeutic screening. PATIENTS AND METHODS: From January 1996 through March 2001 a systematic evaluation of the clinical and the biological thyroid function was performed on a cohort of 84 patients that received supraclavicular irradiation. Selected patients had either a mammary (37 cases) or a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid inspection and palpation, and biological tests: serum FT4 and TSH levels, radioimmunochemistry, completed by dynamic thyroid stimulation, using TRH, in case of border line low T4 or isolated high TSH levels. Tests were repeated every three months the first year, and then every six months. Replacement therapy with L Thyroxin was administered in case of hypothyroidism. RESULTS: All selected patients had a normal function initially. With a mean two years follow up (1-5 years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases) being purely biological. Five patients (11%), with a nasopharyngeal carcinoma, presented also with associated pituitary failure. Clinical symptoms were minor or mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In 2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible predictive factors were evaluated: age of the time of radiation, gender, percentage of irradiated thyroid, total dose, dose per fraction, tumour type and chemotherapy. Only age appeared significantly correlated with thyroid dysfunction (range: 10-30 years, P=0.002). CONCLUSION: Hypothyroidism is a frequent and certainly underestimated complication following radiotherapy of the neck. In such patients, a systematic clinical and biological evaluation every three months the first year, and then every six months until five years is recommended.

[Absorbed dose evaluation of thyroid during nasopharynx and breast carcinoma irradiation by in vivo dosimetry]. / Dosimétrie in vivo pour évaluer la dose reçue par la thyroïde en radiothérapie des cancers du cavum et du sein.

AIMS: The thyroid dysfunction after radiotherapy has led to evaluate the dose received by thyroid during nasopharynx and breast carcinoma irradiation. This evaluation was facilitated by in vivo dosimetry. The aims of this work were to evaluate the thyroid dose and to compare released dose at the reference point in the two localizations. PATIENTS AND METHODS: A total of 30 patients were evaluated: 18 patients with nasopharynx carcinoma and 12 patients with breast carcinoma were included in the final analysis. In the first group, the total thyroid but the isthmus was irradiated. On the other hand, in the second group, only one thyroid lobe was included into the target volume. All patients have been treated by gamma rays of cobalt 60 and the thyroid absorbed dose was measured by semiconductor dosimeters (Scanditronix DPD6). These dosimeters were calibrated in the same geometric conditions of the irradiation. RESULTS: The measured absorbed dose of the thyroid parenchyma was equal to the calculated absorbed dose at the target that has been specified at a depth of -3 cm. Under the block, the isthmus received 5.1 +/- 0.9 Gy (9.9 +/- 1.8%) in nasopharynx carcinoma irradiation. However, in breast carcinoma irradiation, the distal thyroid lobe and the isthmus received 2.9 +/- 0.7 Gy (6.55 +/- 1.56%) and 3.69 +/- 0.77 (8.39 +/- 1.76%), respectively. CONCLUSIONS: This study shows that the thyroid received a dose equal to the prescribed dose in both nasopharynx and breast cancer patients. It is recommended to follow the function of the thyroid gland in these patients.

[Erysipelas after breast cancer treatment]. / Erysipele apres traitement du cancer du sein.

BACKGROUND: Study of the epidemiological, clinical and evolutive characteristics of the erysipelas of patients treated for breast cancer. PATIENTS AND METHODS: Between February 93 and December 99, 20 patients among 700 (2.85%) treated for breast cancer in the radiotherapy department of sfax have presented an erysipelas. All of these patients had undergone a chirurgical treatment containing an axillary lymph node dissection with radiotherapy in 95% and adjuvent chemotherapy in 80% of cases. RESULTS: The medium delay between the appearance of the eryslpelas and the end of treatment was 23 months. The preferential localisation was the homolateral upper limb to the treated breast (95%). The immediate evolution was favourable in 85% after antibiotherapy. Recurrence of erysipelas was seen in 20% in cases. DISCUSSION: Erysipelas after treatment of breast cancer is known but rarely reported. The secondary lymphedema of the upper limb is the major favouring factor. CONCLUSION: Appearance of erysipelas among women treated for breast cancer is frequent, his recurrent character must always lead to antibiotic prophylaxis.