ABSTRACT
BACKGROUND: The EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment. METHODS: Forty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale. RESULTS: There was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients. CONCLUSIONS: Using the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients.
ABSTRACT
PET imaging with 2'-deoxy-2'-[18F]fluoro-D-glucose ([18F]FDG) has become one of the pillars in the management of malignant diseases. It has proven value in diagnostic workup, treatment policy, follow-up, and as prognosticator for outcome. [18F]FDG is widely available and standards have been developed for PET acquisition protocols and quantitative analyses. More recently, [18F]FDG-PET is also starting to be appreciated as a decision aid for treatment personalization. This review focuses on the potential of [18F]FDG-PET for individualized radiotherapy dose prescription. This includes dose painting, gradient dose prescription, and [18F]FDG-PET guided response-adapted dose prescription. The current status, progress, and future expectations of these developments for various tumor types are discussed.
Subject(s)
Fluorodeoxyglucose F18 , Neoplasms , Humans , Positron-Emission Tomography/methods , Neoplasms/diagnostic imaging , Neoplasms/radiotherapy , Glucose , RadiopharmaceuticalsABSTRACT
The aim of this meta-analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma (SCC). For this purpose, MEDLINE, EMBASE, and Web of Science were searched from inception to March 8, 2022. Included were studies evaluating diagnostic test accuracy of SLNB to identify cervical lymph node metastases with elective neck dissection or follow-up as reference. A bivariate generalized linear mixed model approach was used for the meta-analysis. Nineteen studies were eligible, evaluating 377 cases in total. The pooled estimates of sensitivity and negative predictive value were 0.93 (95% CI: 0.86-0.96) and 0.97 (95% CI: 0.94-0.98), respectively. The excellent accuracy of SLNB justifies a place in the diagnostic workup of patients with larynx and pharynx SCC. Randomized trials are required to demonstrate oncologic safety and benefits on treatment related morbidity and quality of life when omitting elective neck treatment based on SLNB.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Larynx , Carcinoma, Squamous Cell/pathology , Diagnostic Tests, Routine , Head and Neck Neoplasms/pathology , Humans , Hypopharynx/pathology , Larynx/pathology , Lymph Nodes/pathology , Oropharynx/pathology , Quality of Life , Sentinel Lymph Node Biopsy , Squamous Cell Carcinoma of Head and Neck/pathologyABSTRACT
Importance: When patient populations in randomized clinical trials deviate too much from the general population, it undermines the relevance for daily practice. Objective: To investigate if patients with head and neck cancer in randomized clinical trials are representative of the clinically treated population. Evidence Review: A systematic literature search was performed for randomized clinical trials on head and neck cancer evaluating an intervention to improve outcome with total sample size of 100 patients or greater and published between 2009 and 2019. Outcome measures were age, performance status, and recruitment rate. National cancer registries provided reference data. Databases that were searched included MEDLINE and Epub Ahead of Print; Embase; Cochrane Central Register of Controlled Trials; and ClinicalTrials.gov. Abstracts of search results were retrieved to assess selection criteria by 2 reviewers independently. After the selection procedure was completed by both reviewers, the results were compared and reviewed once more to reach consensus. Full articles were downloaded to retrieve general study information and outcome data. Findings: A total of 16â¯927 publications were identified, resulting in 87 compliant randomized clinical trials with a total of 34â¯241 patients. Half of the trials included all major head and neck sites, and one-third were exclusively for nasopharynx cancers. The experimental intervention was systemic treatment in 47 (54%) studies, radiotherapy in 23 (26%), and other in 17 (20%). Median sample size was 332, and median duration of accrual was 4.6 years. Median accrual per center per year for head and neck and nasopharynx trials was 5.4 and 39.7 patients, respectively. Median age of patients in head and neck trials was 57 years, which was 7 years younger than in cancer registries. More than 70% of patients had a World Health Organization performance score of 0 to 1 or a Karnofsky performance status of 90 to 100. Conclusions and Relevance: In this systematic review, patients in head and neck randomized clinical trials had a very good performance status, and half of them were younger than 57 years, while half of the clinical population was older than 64 years. In more than 50% of the head and neck trials, the yearly accrual per center was less than 6 patients, suggesting overly restrictive recruitment. Critical appraisal of trial population characteristics is recommended before results are implemented in clinical guidelines and general practice.
Subject(s)
Head and Neck Neoplasms , Head and Neck Neoplasms/therapy , Humans , Middle Aged , Randomized Controlled Trials as TopicSubject(s)
Diagnostic Imaging , Neoplasms , Humans , Neoplasms/diagnostic imaging , Neoplasms/radiotherapyABSTRACT
Advances in diagnostic imaging create opportunities for improved therapeutic targeting of cancer but conceptual thinking about radiotherapy target volume definition and dose-prescription is not keeping up. In this opinion paper we discuss how modern imaging can contribute to new concepts for radiotherapy dose-prescription and target volume definition illustrated by the example of head and neck cancer. These new insights have the potential to significantly reduce radiation associated toxicity and may have important impact on the combination of radiotherapy with systemic cancer therapies.
Subject(s)
Head and Neck Neoplasms , Radiation Injuries , Diagnostic Imaging , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Humans , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
BACKGROUND AND PURPOSE: Multimodality imaging including 18F-FDG-PET has improved the detection threshold of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The aim of this retrospective analysis is to investigate the impact of FDG-PET/CT-based nodal target volume definition (FDG-PET/CT-based NTV) on radiotherapy outcomes, compared to conventional CT-based nodal target volume definition (CT-based NTV). MATERIALS AND METHODS: Six-hundred-thirty-three patients treated for HNSCC with definitive (chemo)radiotherapy using IMRT/VMAT techniques between 2008 and 2017 were analyzed. FDG-PET/CT-based NTV was performed in 46% of the patients. The median follow-up was 31â¯months. Diagnostic imaging depicting the regional recurrence was co-registered with the initial CT-scan to reconstruct the exact site of the recurrence. Multivariate Cox regression analysis was performed to identify variables associated with radiotherapy outcome. RESULTS: FDG-PET/CT-based NTV improved control of disease in the CTVelective-nodal (HR: 0.33, pâ¯=â¯0.026), overall regional control (HR: 0.62, pâ¯=â¯0.027) and overall survival (HR: 0.71, pâ¯=â¯0.033) compared to CT-based NTV. The risk for recurrence in the CTVelective-nodal was increased in case of synchronous local recurrence of the primary tumor (HR: 12.4, pâ¯<â¯0.001). CONCLUSION: FDG-PET/CT-based NTV significantly improved control of disease in the CTVelective-nodal, overall regional control and overall survival compared to CT-based NTV. A significant proportion of CTVelective-nodal recurrences are potentially new nodal manifestations from a synchronous local recurrent primary tumor. These results support the concept of target volume transformation and give an indication of the potential of FDG-PET to guide gradual radiotherapy dose de-escalation in elective neck treatment in HNSCC.
Subject(s)
Fluorodeoxyglucose F18 , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/therapy , Radiotherapy Planning, Computer-Assisted/methods , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/therapy , Chemoradiotherapy , Female , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Positron Emission Tomography Computed Tomography/methods , Proportional Hazards Models , Radiopharmaceuticals , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Survival RateABSTRACT
BACKGROUND AND PURPOSE: Head and neck (HN) radiotherapy can benefit from automatic delineation of tumor and surrounding organs because of the complex anatomy and the regular need for adaptation. The aim of this study was to assess the performance of a commercially available deep learning contouring (DLC) model on an external validation set. MATERIALS AND METHODS: The CT-based DLC model, trained at the University Medical Center Groningen (UMCG), was applied to an independent set of 58 patients from the Radboud University Medical Center (RUMC). DLC results were compared to the RUMC manual reference using the Dice similarity coefficient (DSC) and 95th percentile of Hausdorff distance (HD95). Craniocaudal spatial information was added by calculating binned measures. In addition, a qualitative evaluation compared the acceptance of manual and DLC contours in both groups of observers. RESULTS: Good correspondence was shown for the mandible (DSC 0.90; HD95 3.6 mm). Performance was reasonable for the glandular OARs, brainstem and oral cavity (DSC 0.78-0.85, HD95 3.7-7.3 mm). The other aerodigestive tract OARs showed only moderate agreement (DSC 0.53-0.65, HD95 around 9 mm). The binned measures displayed the largest deviations caudally and/or cranially. CONCLUSIONS: This study demonstrates that the DLC model can provide a reasonable starting point for delineation when applied to an independent patient cohort. The qualitative evaluation did not reveal large differences in the interpretation of contouring guidelines between RUMC and UMCG observers.
ABSTRACT
BACKGROUND: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting. MATERIALS AND METHODS: Ninety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland-Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients. RESULTS: Bland-Altman's analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort. CONCLUSION: The use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches.
Subject(s)
Cervical Cord/diagnostic imaging , Cervical Cord/radiation effects , Fluorodeoxyglucose F18/pharmacokinetics , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Adult , Aged , Cervical Cord/metabolism , Cohort Studies , Female , Head and Neck Neoplasms/metabolism , Humans , Male , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Regression Analysis , Reproducibility of Results , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/metabolism , Tumor BurdenABSTRACT
Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15â¯mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity.
Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Aged , Female , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Lymphatic Metastasis , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Radiotherapy Dosage , Tumor BurdenABSTRACT
BACKGROUND: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. METHODS: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). DISCUSSION: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02442375 .
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/radiotherapy , Positron-Emission Tomography/methods , Radiotherapy Dosage , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/diagnostic imaging , Female , Head and Neck Neoplasms/diagnostic imaging , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Quality of Life , Radiation Injuries/prevention & control , Radiotherapy Planning, Computer-Assisted/methods , Single-Blind MethodABSTRACT
BACKGROUND: The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. METHODS: We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. CONCLUSION: Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Radiation Injuries/prevention & control , Radiotherapy, Intensity-Modulated/methods , Re-Irradiation/adverse effects , Adult , Aged , Cohort Studies , Disease-Free Survival , Female , Follow-Up Studies , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Proportional Hazards Models , Radiotherapy, Adjuvant , Radiotherapy, Intensity-Modulated/adverse effects , Re-Irradiation/methods , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer. METHODS AND MATERIALS: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated. The exact sites of regional recurrences were reconstructed and projected on the initial radiation therapy planning CT scan by performing coregistration with diagnostic imaging of the recurrence. RESULTS: The actuarial rate of recurrence in electively irradiated lymph node regions at 2 years was 5.1% (95% confidence interval 2.4%-7.8%). Volumetric analysis showed an increased risk of recurrence with increasing nodal volume. Receiver operating characteristic analysis demonstrated that the summed long- and short-axis diameter is a good alternative for laborious volume calculations, using ≥17 mm as cut-off (hazard ratio 17.8; 95% confidence interval 5.7-55.1; P<.001). CONCLUSIONS: An important risk factor was identified that can help clinicians in the pretreatment risk assessment of borderline-sized lymph nodes. Not overtly pathologic nodes with a summed diameter ≥17 mm may require a higher than elective radiation therapy dose. For low-risk elective regions (all nodes <17 mm), the safety of dose de-escalation below the traditional 45 to 50 Gy should be investigated.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Lymph Nodes/radiation effects , Lymphatic Irradiation , Neoplasm Recurrence, Local , Radiotherapy, Intensity-Modulated/methods , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Confidence Intervals , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Hypopharyngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/radiotherapy , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/radiotherapy , Radiotherapy Dosage , Risk Assessment , Tumor BurdenABSTRACT
BACKGROUND: Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania. METHODS: In a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1 km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period. RESULTS: The coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2). CONCLUSIONS: This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity. The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00509015.
Subject(s)
Antimalarials/administration & dosage , Malaria/prevention & control , Malaria/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Artemisinins/administration & dosage , Artesunate , Child , Child, Preschool , Drug Combinations , Drug Therapy, Combination/methods , Endemic Diseases/prevention & control , Female , Humans , Infant , Male , Microscopy , Middle Aged , Parasitemia/diagnosis , Placebos/administration & dosage , Primaquine/administration & dosage , Pyrimethamine/administration & dosage , Sulfadoxine/administration & dosage , Tanzania/epidemiology , Treatment Outcome , Young AdultABSTRACT
CONTEXT: Some studies report that tumour progression in patients with non-muscle-invasive bladder cancer (NMIBC) is associated with a poor prognosis. However, no systematic evidence is available. OBJECTIVE: The aim of the study was to systematically review literature to determine the long-term cancer-specific survival in patients with high-risk NMIBC (T1G3, multifocal, highly recurrent, or carcinoma in situ) having tumour progression. EVIDENCE ACQUISITION: A systematic review was conducted by searching PubMed and the Cochrane library for studies published between 2006 and 2011. Additional studies were identified by scanning reference lists of relevant papers. We attempted to retrieve missing data by contacting the corresponding author. Keywords used included bladder cancer, high-risk, high grade, carcinoma in situ, non-muscle invasive bladder cancer, progression, and survival. Studies were included when they met the following criteria: inclusion of at least 75 patients having high-risk NMIBC, patients were initially treated conservatively with transurethral resection of the bladder tumour and intravesical instillations, a median follow-up of at least 48 mo, and reporting data on progression to muscle-invasive bladder cancer (MIBC) and death resulting from bladder cancer (BCa). EVIDENCE SYNTHESIS: Literature was systematically reviewed, and 19 trials were included, producing a total of 3088 patients, of which 659 (21%) showed progression to MIBC and 428 (14%) died as a result of BCa after a median follow-up of 48-123 mo. Survival after progression from high-risk NMIBC to MIBC was 35%. Progression to MIBC and BCa-related death in high-risk NMIBC were found to be relatively early events, occurring mainly within 48 mo. Finally, even in cases of early cystectomy in patients with high-risk NMIBC, a relevant proportion of these patients appear not be cured of their disease. CONCLUSIONS: This study provides systematically gathered evidence showing a poor prognosis for patients with high-risk NMIBC and tumour progression.
Subject(s)
Carcinoma/mortality , Carcinoma/pathology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Carcinoma/surgery , Cystectomy , Disease Progression , Evidence-Based Medicine , Humans , Risk Assessment , Risk Factors , Survival Rate , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/surgery , Urothelium/pathologyABSTRACT
BACKGROUND: Postpyloric enteral feeding often requires endoscopic or fluoroscopic placement of a feeding tube. Self-propelled feeding tubes are designed to facilitate spontaneous migration into the jejunum. This study aimed to assess the rate of success and time to migrate a self-propelled feeding tube to jejunal position using erythromycin, a prokinetic agent. METHODS: Non-critically ill patients with pancreatitis who required jejunal enteral feeding were included. A self-propelled nasoenteric feeding tube was placed into the stomach using either placebo or erythromycin. At 24 and 48 hours after initial placement, an abdominal x-ray was taken to determine the position of the tube. RESULTS: Forty subjects were included and randomized. After 48 hours, there was no difference in the rates of success between placebo 56% (9/16) and erythromycin 50% (10/20) (P = .71). CONCLUSIONS: Self-propelled feeding tubes migrated into the jejunum in 53% of the subjects within 48 hours. However, this study failed to determine any benefit of erythromycin in terms of success or time to migrate to jejunal position using a self-propelled feeding tube. Selection of subjects without impaired motility and tachyphylaxis may have contributed to clinical failure of erythromycin as a prokinetic agent in this study.
Subject(s)
Enteral Nutrition , Erythromycin/therapeutic use , Gastrointestinal Agents/therapeutic use , Intubation, Gastrointestinal/methods , Pancreatitis/therapy , Adult , Aged , Aged, 80 and over , Double-Blind Method , Enteral Nutrition/instrumentation , Enteral Nutrition/methods , Female , Humans , Intubation, Gastrointestinal/instrumentation , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the hemolytic effect of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) plus a single dose of primaquine (PQ; 0.75 mg/kg of body weight) in children aged 1 to 12 years. Children were randomized to receive SP+AS+PQ or placebo; those with a hemoglobin (Hb) level below 8 g/dl were excluded from receiving PQ and received SP+AS. The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment. This reduction in Hb was most pronounced in G6PD-deficient (G6PD A-) individuals (-2.5 g/dl; 95% confidence interval [95% CI], -1.2 to -3.8 g/dl) but was also observed in heterozygotes (G6PD A) (-1.6 g/dl; 95% CI, -0.9 to -2.2 g/dl) and individuals with the wild-type genotype (G6PD B) (-0.5 g/dl; 95% CI, -0.4 to -0.6 g/dl). Moderate anemia (Hb level of <8 g/dl) was observed in 40% (6/15 individuals) of the G6PD A-, 11.1% (3/27 individuals) of the G6PD A, and 4.5% (18/399 individuals) of the G6PD B individuals; one case of severe anemia (Hb level of <5 g/dl) was observed. PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis.