Incidence and predictive factors of retropharyngeal lymph node metastases in patients with oropharyngeal cancer undergoing multimodality treatment planning imaging.

BACKGROUND: We investigated the incidence and predictive factors of retropharyngeal lymph node (RPLN) metastases in patients with oropharyngeal cancer (OPC) undergoing multimodality treatment planning imaging before radiotherapy. METHODS: Consecutive patients with OPC treated with curative-intent radiotherapy from 2017 to 2019 were retrospectively analyzed. Treatment planning comprised contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET) unless contraindicated. RESULTS: Of 300 patients, 66 (22%) had radiological evidence of RPLN involvement on planning images, compared to 17 (6%) on diagnostic CT alone. On multivariate analysis, RPLN involvement was statistically (p < 0.05) associated with tonsil, soft palate, and posterior pharyngeal wall primaries, and with disease extension to the soft palate or vallecula. CONCLUSIONS: Multimodality treatment planning imaging reveals a high rate of RPLN metastases from OPC compared to diagnostic CT alone. Patients with tonsil, soft palate, or posterior pharyngeal wall primaries or disease extending to the soft palate or vallecula appear at higher risk.

Should Magnetic Resonance Angiography Be Used for Screening of Intracranial Aneurysm in Adults with Sickle Cell Disease?

Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs in asymptomatic adult patients with SCD referred from the SCD clinic for routine screening by MRI/MRA using a 3T-MRI scanner. Findings were independently reviewed by two neuroradiologists. Between 2016 and 2020, 245 asymptomatic adults with SCD were stratified according to genotype (SS/S-ß0thalassemia and SC/Sß+). ICANs were found in 27 patients (11%; 0.95 CI: 8-16%). ICANs were more frequent in SS/S-ß0thalassemia patients (20/118 or 17%; 0.95 CI: 11-25%) than in SC/ßb+ patients (7/127 or 6%; 0.95 CI: 2-11%; p = 0.007). Individuals with SCD (particularly SS/S-ß0thalassemia) have a higher prevalence of ICANs than the general population. We believe that MRA should be considered in the current American Society of Hematology guidelines, which already contain a recommendation for MRI at least once in adult SCD patients. However, the clinical significance of preventive treatment of unruptured aneurysms remains controversial.

Phase II study of de-intensified intensity-modulated radiotherapy and concurrent carboplatin/5-fluorouracil in lateralized p16-associated oropharyngeal carcinoma.

PURPOSE: To assess cancer control and patient-reported outcomes (PROs) after de-intensified intensity-modulated radiotherapy (IMRT) in lateralized p16-associated oropharyngeal cancer (p16-OPC). METHODS: Lateralized p16-OPC treated with radiotherapy and concurrent Carboplatin/5-fluorouracil between 2011 and 2014 were enrolled. De-intensified IMRT consisted in elective neck dose of 43.2 Gy/24 fractions and omission of contralateral retropharyngeal/level IV nodes. PROs were assessed using the EORTC QLC-C30 and QLQ-HN35 scales. RESULTS: Twenty-nine patients were included. Median follow-up was 44 months. As per AJCC 7th Ed, 7%, 83% and 10% of patients had stage III, IVa and IVb. 5-year locoregional control and overall survival rates were 100% and 100%, respectively. Rates of acute were 52% and 35%, respectively. At 2 years post-treatment, 50% and 14% of patients had grade 1 xerostomia and dysgueusia, respectively. Most PROs scores returned to baseline within 8 months post-treatment. CONCLUSION: De-intensified IMRT was associated with excellent cancer outcomes, and rapid recovery of PROs in lateralized p16-OPC.

Diagnostic Reliability of Leptomeningeal Disease Using Magnetic Resonance Imaging.

Brain metastases are seen in 20%-50% of patients with metastatic solid tumors. On the other hand, leptomeningeal disease (LMD) occurs more rarely. The gold standard for the diagnosis of LMD is serial cerebrospinal fluid (CSF) analyses, although in daily practice, the diagnosis of LMD is often made by neuroimaging. Leptomeningeal metastases (LM) have been a relative contra-indication to radiosurgery. It can be noted that focal LMD can be difficult to distinguish from a superficially located/cortical-based brain metastasis which is not a contra-indication for radiosurgery. Hence, justifying the need of a reliable diagnosis method. The goal of this study was to determine the inter-observer reliability of contrast-enhanced magnetic resonance imaging (gdMRI) in the differentiation of focal cortical-based metastases from leptomeningeal spread. This is a retrospective review of a prospectively collected database of patients with brain metastases. A total of 42 cases with superficial lesions were selected for review. Additionally, eight control cases demonstrating deep and/or white-matter based lesions were included in the study. Three neuroradiologists and three radiation oncologists were asked to review each study and score the presence of LM. Inter-observer agreement was calculated using group-derived agreement coefficients (Gwet's AC1 and Gwet's AC2). Pair-wise inter-observer agreement coefficients never reached substantial values for trichotomized outcomes (LMD, non-LMD or indeterminate) but did reach a substantial value in a minority of cases for dichotomised outcomes (LMD or non-LMD). The control subgroup analysis revealed substantial agreement between most pairs for both trichotomized and dichotomised outcomes. We observed low inter-observer agreement amongst specialists for the diagnosis of focal LMD by gdMRI. Neuroimaging should not be relied upon to make treatment decisions, notably to deny patients radiosurgery.

Low-Energy Virtual Monochromatic Dual-Energy Computed Tomography Images for the Evaluation of Head and Neck Squamous Cell Carcinoma: A Study of Tumor Visibility Compared With Single-Energy Computed Tomography and User Acceptance.

OBJECTIVE: Dual-energy computed tomography (CT) 40-keV virtual monochromatic images (VMIs) have been reported to improve visualization of head and neck squamous cell carcinoma, but a direct comparison to single-energy CT (SECT) is lacking, and there is debate regarding subjective user preference. We compared 40-keV VMIs with SECT and performed a subjective evaluation of their utility and acceptability for clinical use. METHODS: A total of 60 dual-energy CT and 60 SECT scans from 2 different institutions were evaluated. Tumor conspicuity was evaluated objectively using absolute and relative attenuation and subjectively by 3 head and neck specialists and 3 general radiologists. RESULTS: Tumors had significantly higher absolute and relative attenuation on 40-keV VMIs (P < 0.0001). Subjectively, the 40-keV VMIs improved visualization, with substantial (κ, 0.61-0.80) to almost perfect (κ, 0.81-1) interrater agreements. CONCLUSIONS: The 40-keV VMIs improve tumor visibility objectively and subjectively both by head and neck specialists and general radiologists.

Postoperative diffusion weighted MRI and preoperative CT scan fusion for residual cholesteatoma localization.

OBJECTIVE: To evaluate the ability of preoperative mastoid high resolution Computerized tomography (CT Scan) fusion with the postoperative diffusion weighted magnetic resonance imaging (Non-EPI DWI) to accurately localize the residual cholesteatoma thus sparing an unnecessary postoperative CT scan radiation. PATIENTS AND METHODS: this is a prospective study performed in our tertiary care center. We followed up prospectively a consecutive group of patients presenting with middle ear cholesteatoma using preoperative mastoid CT scans, postoperative mastoid CT scan and mastoid diffusion weighted MRI (DWI) between 2012 and 2013. Postoperative DWI were fused to both: the preoperative and postoperative mastoid CT scans. Fused images were evaluated for their ability to detect accurately the location of residual cholesteatoma if any. Results were correlated to the surgical findings. RESULTS: Twenty-eight patients were included in this study. Ten patients showed middle ear opacity on the postoperative CT scans; the remaining negatively patients were excluded. DWI detected residual cholesteatoma in 3 out of the ten patients. Both CT scans; the pre and postoperative were able to precisely localize the residual cholesteatoma when fused to the postoperative DWI. Intra-operatively, three patients had a residual cholesteatoma that corresponded to the fused radiological images while a fourth patient presenting low signal intensity on the Non-EPI DWI had no cholesteatoma. CONCLUSION: Diffusion weighted MRI/CT scan fusion combines the advantages of residual cholesteatoma detection and precise localization. Preoperative CT scans performed before the first surgery can be used for the fusion with the Non-EPI DWI in order to spare the patient an unnecessary another CT scan and thus decreasing radiation exposure.

The relevance of preoperative ultrasound cervical mapping in patients with thyroid cancer.

BACKGROUND: Cervical lymph node involvement in thyroid cancer is associated with locoregional recurrence and decreased disease-free survival. Preoperative lymph node mapping helps in planning surgery for neck dissection and improves patient outcomes. We sought to perform a qualitative and quantitative analysis of ultrasound mapping for thyroid cancer and evaluate the clinical importance of this exam in terms of identifying the group of patients who would benefit most from subsequent surgical dissection. METHODS: We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery between 2009 and 2013. We calculated the positive predictive values (PPVs) of ultrasound mapping of both the lateral and central compartments together and the lateral or central compartment individually. A quantitative analysis was performed by comparing the number of positive lymph nodes at ultrasound imaging with histopathologic evaluation. RESULTS: A total of 136 cases of thyroid cancer in 120 patients met the inclusion criteria for ultrasound mapping analysis. The PPVs (and 95% confidence intervals) were 83.82 (0.76-0.89) for the lateral and central compartments, 85.39% (0.76-0.91) for the lateral compartment, and 80.48% (0.7-0.87) for the central compartment. When comparing the positive lymph nodes at ultrasound imaging with histopathologic evaluation, the result was χ(2) = 10.33 (p = 0.006). CONCLUSION: This single-institution study indicated that preoperative ultrasound mapping is an accurate imaging procedure for predicting lymphatic spread in differentiated and medullary thyroid cancer. Ultrasound mapping can be used as an efficient tool for surgical planning and prognosis determination, as well as for identifying the group of patients who would benefit most from subsequent surgical intervention.

CONTEXTE: Dans le contexte du cancer de la thyroïde, l'envahissement des noeuds lymphatiques cervicaux est associé à une récidive locorégionale et à une diminution de la survie sans récidive. Une cartographie préopératoire des noeuds lymphatiques facilite la planification de la dissection du cou et améliore les résultats pour les patients. Nous avons procédé à une analyse qualitative et quantitative de la cartographie par ultrasons dans le contexte du cancer de la thyroïde et avons évalué l'utilité de cette technique sur le plan clinique pour cibler le groupe de patients chez qui une dissection chirurgicale subséquente est indiquée. MÉTHODES: Nous avons évalué rétrospectivement les dossiers de 263 patients ayant subi une thyroïdectomie entre 2009 et 2013. Nous avons calculé la valeur prédictive positive dans le contexte d'une cartographie par ultrasons du compartiment latéral et du compartiment central, conjointement et individuellement. Nous avons ensuite effectué une analyse quantitative en comparant le nombre de noeuds lymphatiques positifs détectés avec la cartographie par ultrasons et l'examen histopathologique. RÉSULTATS: En tout, 136 cas de cancers de la thyroïde, ayant touché 120 patients, respectaient les critères d'inclusion de l'analyse. La valeur prédictive positive était de 83,82 % (0,76­0,89) pour la cartographie conjointe des compartiments latéral et central; de 85,39 % (0,76­0,91) pour le compartiment latéral; et de 80,48 % (0,7­0,87) pour le compartiment central (intervalle de confiance de 95 %). En comparant les résultats de l'imagerie avec ceux de l'examen histopathologique, nous avons obtenu un résultat de χ2 = 10,33 (p = 0,006). CONCLUSION: Menée auprès de patients d'un seul établissement, cette étude a permis de conclure que la cartographie préopératoire par ultrasons est une technique d'imagerie médicale fiable qui permet de prévoir l'envahissement lymphatique chez les patients atteints d'un cancer médullaire ou différencié de la thyroïde. Cette technique peut être utilisée pour planifier une intervention chirurgicale ou établir un pronostic ainsi que pour cibler le groupe de patients chez qui une dissection chirurgicale subséquente serait indiquée.

DRESS syndrome: cerebral vasculitic-like presentation.

INTRODUCTION: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is a severe adverse drug-induced reaction. It manifests with pyrexia, eosinophilia, and lymphadenopathy, with multiple organ involvement, mainly the skin, liver, and kidneys. The purpose of this article is to demonstrate that DRESS syndrome can be associated with cerebral manifestations, a concept not well known in the neuroradiological literature. METHODS: We describe three cases of DRESS syndrome associated with cerebral vasculitic-like lesions and realize a review of the literature to demonstrate that this association represents a very rare entity. RESULTS: Acute ischemic lesions were found among two patients. In all cases, perivascular enhancement was present. Magnetic resonance angiography (MRA) sequence was normal. Although no cerebral biopsy was performed, this enhancement pattern is strongly suggestive of a vasculitic process associated with DRESS syndrome. CONCLUSION: Diagnosis of cerebral vasculitic-like associated lesions must be considered in patients with DRESS syndrome since it can be reversed completely by withdrawing the causal medication and instigating corticosteroid treatment in a timely fashion.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

BACKGROUND: In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. METHODS: The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). RESULTS: Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. CONCLUSION: This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria.

Retropharyngeal calcific tendinitis mimicking a retropharyngeal phlegmon.

Background. Acute retropharyngeal tendinitis is a little known but not an uncommon condition. It was first described by Hartley in 1964 as an inflammation of the longus colli muscle secondary to calcium crystals deposition on its insertion. The calcifications are mostly located on the oblique portion of the muscle at the level of C1-C2. Methods. We will describe this disease through 4 cases that presented in our institution. Results. The most common symptoms are severe neck pain, odynophagia, and a painful restriction of neck movement. It is associated with mild fever and inflammatory lab findings such as a slight elevation of white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. CT scan is recommended as the first-line imaging modality to establish a diagnosis. Treatments consist of NSAIDs and analgesics to accelerate the healing process. If symptoms are severe, a course of corticosteroids is required. Conclusion. Since the clinical and laboratory findings of this condition and those of a retropharyngeal abscess overlap, it is important to establish the right diagnosis in order to prevent more invasive procedures. A good knowledge of this clinical entity by otolaryngologists would prevent delays in hospital discharge and unnecessary anxiety.

Prognostic value of cartilage sclerosis in laryngeal cancer treated with primary radiation therapy.

OBJECTIVE: In patients with laryngeal cancer, pretreatment diagnosis of cartilage invasion often warrants a surgical or a bimodal treatment. Controversy exists on whether laryngeal cartilage sclerosis on computed tomography (CT) scan is a sign of tumor invasion. Our objective is to evaluate locoregional, laryngectomy-free, disease-specific, and overall survival in patients with laryngeal cancer with or without laryngeal cartilage sclerosis treated with primary radiation therapy. STUDY DESIGN: Historical cohort study. SETTING: Tertiary referral university center. SUBJECTS AND METHODS: All laryngeal cancer patients treated with primary radiation therapy between 2002 and 2007 were included. Patients with and without laryngeal cartilage sclerosis on CT scan were identified. Patient, tumor, and treatment data were collected. Univariate and multivariate analyses were conducted using Kaplan-Meier survival analyses and Cox proportional-hazards regression. RESULTS: One hundred eleven patients were included for analysis. Seventy-nine patients were classified as T1 or T2, and 32 patients were classified as T3 or T4. Twenty-three percent of patients had any laryngeal cartilage sclerosis, and 77% of patients had no sclerosis. On univariate and multivariate analyses, there was no statistically significant difference between patients with or without sclerosis. Results did not vary when studying each cartilage separately. CONCLUSION: Laryngeal cancer patients with cartilage sclerosis on CT scan do not have significantly different survival than patients without sclerosis. Validation of these results prospectively is warranted.

The role of computed tomography in the management of the neck after chemoradiotherapy in patients with head-and-neck cancer.

PURPOSE: The aim of this study was to describe the outcome in patients with head-and neck-squamous cell carcinoma (HNSCC) followed up without neck dissection (ND) after concomitant chemoradiotherapy (CRT) based on computed tomography (CT) response. The second objective was to establish CT characteristics that can predict which patients can safely avoid ND. METHODS AND MATERIALS: Between 1998 and 2007, 369 patients with node-positive HNSCC were treated with primary CRT at our institution. After a clinical and a radiologic evaluation based on CT done 6 to 8 weeks after CRT, patients were labeled with a complete neck response (CR) or with a partial neck response (PR). RESULTS: The median follow-up was 44 months. The number of patients presenting with N3, N2, or N1 disease were 54 (15%), 268 (72%), and 47 (13%), respectively. After CRT, 263 (71%) patients reached a CR, and 253 of them did not undergo ND. Ninety-six patients reached a PR and underwent ND. Of those, 34 (35%) had residual disease on pathologic evaluation. A regression of the diameter of ≥ 80% and a residual largest diameter of 15 mm of nodes had negative pathologic predictive values of 100% and 86%, respectively. The 3-year regional control and survival rates were not different between patients with CR who had no ND and patients with PR followed by ND. CONCLUSION: Node-positive patients presenting a CR as determined by CT evaluation 6 to 8 weeks after CRT had a low rate of regional recurrence without ND. This study also suggests that lymph node residual size and percentage of regression on CT after CRT may be useful criteria to guide clinical decisions regarding neck surgery. Those results can help diminish the number of ND procedures with negative results and their associated surgical complications.

¹8F-FDG-PET imaging in radiotherapy tumor volume delineation in treatment of head and neck cancer.

PURPOSE: To determine the impact of (18)F-fluorodeoxyglucose positron emission tomography (PET) in radiotherapy target delineation and patient management for head and neck squamous cell carcinoma (HNSCC) compared to computed tomography (CT) alone. MATERIALS AND METHODS: Twenty-nine patients with HNSCC were included. CT and PET/CT obtained for treatment planning purposes were reviewed respectively by a neuroradiologist and a nuclear medicine specialist who were blinded to the findings from each other. The attending radiation oncologist together with the neuroradiologist initially defined all gross tumor volume of the primary (GTVp) and the suspicious lymph nodes (GTVn) on CT. Subsequently, the same radiation oncologist and the nuclear medicine specialist defined the GTVp and GTVn on (18)F-FDG-PET/CT. Upon disagreement between CT and (18)F-FDG-PET on the status of a particular lymph node, an ultrasound-guided fine needle aspiration was performed. Volumes based on CT and (18)F-FDG-PET were compared with a paired Student's t-test. RESULTS: For the primary disease, four patients had previous diagnostic tonsillectomy and therefore, FDG uptake occurred in 25 patients. For these patients, GTVp contoured on (18)F-FDG-PET (GTVp-PET) were smaller than the GTVp contoured on CT (GTVp-CT) in 80% of the cases, leading to a statistically significant volume difference (p=0.001). Of the 60 lymph nodes suspicious on PET, 55 were also detected on CT. No volume change was observed (p=0.08). Ten biopsies were performed for lymph nodes that were discordant between modalities and all were of benign histology. Distant metastases were found in two patients and one had a newly diagnosed lung adenocarcinoma. CONCLUSIONS: GTVp-CT was significantly larger when compared to GTVp-PET. No such change was observed for the lymph nodes. (18)F-FDG-PET modified treatment management in three patients, including two for which no curative radiotherapy was attempted. Larger multicenter studies are needed to ascertain whether combined (18)F-FDG-PET/CT in target delineation can influence the main clinical outcomes.

Enteral feeding during chemoradiotherapy for advanced head-and-neck cancer: a single-institution experience using a reactive approach.

PURPOSE: The optimal method for providing enteral nutrition to patients with head-and-neck cancer is unclear. The purpose of the present study was to evaluate the safety and efficacy of our reactive policy, which consists of the installation of a nasogastric (NG) feeding tube only when required by the patient's nutritional status. METHODS AND MATERIALS: The records of all patients with Stage III and IV head-and-neck cancer treated with concomitant chemotherapy and radiotherapy between January 2003 and December 2006 were reviewed. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The present study included 253 patients, and the median follow-up was 33 months. At 3 years, the estimated overall survival and disease-free survival rate was 82.8% and 77.8%, respectively, for the whole population. No survival difference was observed when the patients were compared according to the presence and absence of a NG tube or stratified by weight loss quartile. The mean weight loss during treatment for all patients was 10.4%. The proportion of patients requiring a NG tube was 49.8%, and the NG tube remained in place for a median duration of 40 days. No major complications were associated with NG tube installation. Only 3% of the patients were still dependent on enteral feeding at 6 months. CONCLUSION: These results suggest that the use of a reactive NG tube with an interdisciplinary team approach is a safe and effective method to manage malnutrition in patients treated with concomitant chemotherapy and radiotherapy for head-and-neck cancer.

Outcome with neck dissection after chemoradiation for N3 head-and-neck squamous cell carcinoma.

PURPOSE: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. METHODS AND MATERIALS: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND after partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. RESULTS: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). CONCLUSIONS: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.

Organ preservation with concurrent chemoradiation for advanced laryngeal cancer: are we succeeding?

PURPOSE: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). METHODS AND MATERIALS: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. RESULTS: Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. CONCLUSIONS: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.

The polymorphic nature of HIV type 1 env V4 affects the patterns of potential N-glycosylation sites in proviral DNA at the intrahost level.

We have previously shown that env V4 from HIV-1 plasma RNA is highly heterogeneous within a single patient, due to indel-associated polymorphism. In this study, we have analyzed the variability of V4 in proviral DNA from unfractionated PBMC and sorted T and non-T cell populations within individual patients. Our data show that the degree of sequence variability and length polymorphism in V4 from HIV provirus is even higher than we previously reported in plasma. The data also show that the sequence of V4 depends largely on the experimental approach chosen. We could observe no clear trend for compartmentalization of V4 variants in specific cell types. Of interest is the fact that some variants that had been found to be predominant in plasma were not detected in any of the cell subsets analyzed. Consistently with our observations in plasma, V3 was found to be relatively conserved at both interpatient and intrapatient level. Our data show that V4 polymorphism involving insertions and deletions in addition to point mutations results in changes in the patterns of sequons in HIV-1 proviral DNA as well as in plasma RNA. These rearrangements may result in the coexistence, within the same individual, of a swarm of different V4 regions, each characterized by a different carbohydrate surface shield. Further studies are needed to investigate the mechanism responsible for the variability observed in V4 and its role in HIV pathogenesis.