This study assessed the delivered dose accuracy in pancreas SBRT by incorporating the real-time target position determined using an in-house position monitoring system.
An online image-based position ...monitoring system, SeedTracker, was developed to monitor radiopaque marker positions using monoscopic x-ray images, available from the Elekta XVI imaging system. This system was applied to patients receiving SBRT for pancreatic cancer on the MASTERPLAN Pilot trial (ACTRN 12617001642370). All patients were implanted pre-treatment with at least three peri-tumoral radiopaque markers for target localisation. During treatment delivery, marker positions were compared to expected positions delineated from the planning CT. The position tolerance of ±3mm from the expected position of the markers was set to trigger a gating event (GE) during treatment. The dosimetric impact of position deviations and actual dose delivered with position corrections was assessed by convolving the plan control point dose matrices with temporal target positions determined during treatment.
Eight patients were treated within this study. At least one GE was observed in 38% of the treatment fractions and more than one GE was observed in 10% of the fractions. The position deviations resulted in the mean(range) difference of -0.1(-1.1 - 0.4)Gy in minimum dose to tumour and 1.9(-0.1- 4.6)Gy increase to Dmax to duodenum compared to planned dose. In actual treatment delivery with the patient realignment, the mean difference of tumour min dose and duodenal Dmax was reduced to 0.1(-1.0 - 1.1)Gy and 1.1 (-0.7 - 3.3)Gy respectively compared to the planned dose.
The in-house real-time position monitoring system improved the treatment accuracy of pancreatic SBRT in a general-purpose linac and enabled assessment of delivered dose by incorporating the temporal target position during delivery. The intrafraction motion impacts the dose to tumour even if target position is maintained within a 3mm position tolerance.
Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive alternative technique for mediastinal staging of non-small cell lung cancer. A metaanalysis was performed to ...estimate the diagnostic accuracy of EUS-FNA for staging mediastinal lymph nodes (N2/N3 disease) in patients with lung cancer.
Relevant studies were identified using Medline (1966 to November 2005), CINAHL, and citation indexing. Included studies used histology or adequate clinical follow-up (> 6 months) as the "gold standard," and provided sufficient data for calculating sensitivity and specificity. Summary receiver operating characteristic curves metaanalysis was performed to estimate the pooled sensitivity and specificity.
In 18 eligible studies, EUS-FNA identified 83% of patients (95% confidence interval CI, 78 to 87%) with positive mediastinal lymph nodes (pooled sensitivity) and 97% of patients (95% CI, 96 to 98%) with negative mediastinal lymph nodes (pooled specificity). In eight studies that were limited to patients who had abnormal mediastinal lymph nodes seen on CT scans, the sensitivity was 90% (95% CI, 84 to 94%) and the specificity was 97% (95% CI, 95 to 98%). In patients without abnormal mediastinal lymph nodes seen on CT scans (four studies), the pooled sensitivity was 58% (95% CI, 39 to 75%). Minor complications were reported in 10 cases (0.8%). There were no major complications.
EUS-FNA is a safe modality for the invasive staging of lung cancer that is highly sensitive when used to confirm metastasis to mediastinal lymph nodes seen on CT scans. In addition, among lung cancer patients with normal mediastinal adenopathy seen on CT scans, despite lower sensitivity, it has the potential to prevent unnecessary surgery in a large proportion of cases missed by CT scanning.
Background The management strategies for Barrett's esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and ...esophagectomy. Objective To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD. Design Multicenter U.S. registry. Setting Sixteen academic and community centers; treatment period from September 2004 to March 2007. Patients Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation. Intervention Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment. Outcomes Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM). Results A total of 142 patients (median age 66 years, interquartile range IQR 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%. Limitations A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up. Conclusions Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.
Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop ...EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.
Upper-GI vascular ectasias, including angiodysplasia and gastric antral vascular ectasia may present with either acute or chronic bleeding. Endoscopic thermal modalities have been used to control ...acute bleeding and reduce transfusion requirements.
Endoscopic experience was reviewed for a 6-year period during which 32 patients requiring blood transfusions for upper-GI angiodysplasia or gastric antral vascular ectasia were evaluated. Patients seen during the first 5 years were treated with either Nd:YAG laser photocoagulation or multipolar electrocoagulation. During the most recent 12 months, all patients were treated by argon plasma coagulation. Response to therapy was assessed by change in mean Hb and transfusion requirements.
Overall, 16 patients were treated by laser photoablation alone; 9, argon plasma coagulation with or without laser; and 7, multipolar electrocoagulation with or without laser. Mean follow-up for all patients was 19 months. After therapy, mean Hb concentration rose from 76 to 114 g/L for patients with gastric antral vascular ectasia and from 85 to 118 g/L for those with angiodysplasia. Endoscopic therapy abolished or reduced transfusion requirements in 93% of patients with gastric antral vascular ectasia and 76% with angiodysplasia. Patients with gastric antral vascular ectasia required a mean of 6 treatment sessions, while those with angiodysplasia required one to two sessions.
Endoscopic thermal ablation effectively controls acute bleeding and reduces transfusion requirements in most patients with upper-GI vascular ectasias. Patients with gastric antral vascular ectasia require significantly more treatment sessions to achieve this effect.
The causal link between high‐risk human papillomavirus (hr‐HPV) infection and cervical, anogenital, and some oropharyngeal malignancies has been established by both molecular and epidemiological ...data. The association between HPV and esophageal squamous cell carcinoma (ESCC) remains controversial, as is the true prevalence of HPV infection in ESCC. The wide range in reported rates reflects variability in the primary literature, with some larger scale case–control studies suggesting the infection rates range from 0% to 78%. Interactions between HPV and the Barrett's metaplasia–dysplasia–carcinoma sequence have been explored, and these studies have shown some conflicting data. Overall, systematic reviews have reported the prevalence of HPV‐positive DNA in esophageal adenocarcinoma patients of between 13% and 35%. Postulated reasons for discrepancies in HPV prevalence rates in esophageal cancer include variations in testing methodology and assay sensitivities; technical issues, including the lack of a gold‐standard primer; types of specimens utilized (fresh‐frozen versus formalin‐fixed tissue); geographical variation; cross‐contamination; and small sample sizes. Thus, efforts must be undertaken to (1) standardize HPV testing, ideally in a central laboratory and utilizing tests that detect viral transcriptional activity; (2) avoid cross‐contamination; and (3) recruit large numbers of patients to accurately ascertain HPV rates in esophageal malignancy.
The role of EUS to evaluate subtle radiographic abnormalities of the pancreas is not well defined.
To assess the yield of EUS+/-FNA for focal or diffuse pancreatic enlargement/fullness seen on ...abdominal CT scan in the absence of discrete mass lesions.
Retrospective database review.
Tertiary referral center.
Six hundred and 91 pancreatic EUS exams were reviewed. Sixty-nine met inclusion criteria of having been performed for focal enlargement or fullness of the pancreas. Known chronic pancreatitis, pancreatic calcifications, acute pancreatitis, discrete mass on imaging, pancreatic duct dilation (greater than 4 mm) and obstructive jaundice were excluded.
Rate of malignancy found by EUS+/-FNA.
FNA was performed in 19/69 (27.5%) with 4 new diagnoses of pancreatic adenocarcinoma, one metastatic renal cell carcinoma, one metastatic colon cancer, one chronic pancreatitis and 12 benign results. Eight patients had discrete mass lesions on EUS; two were cystic. All malignant diagnoses had a discrete solid mass on EUS.
Pancreatic enlargement/fullness is often a benign finding related to anatomic variation, but was related to malignancy in 8.7% of our patients (6/69). EUS should be strongly considered as the next step in the evaluation of patients with focal enlargement of the pancreas when clinical suspicion of malignancy exists.
We have previously demonstrated that transcriptionally active high‐risk HPV (hr‐HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh ...frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin‐fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6/E7, respectively. Prospectively, BM (n = 81)/BD (n = 72)/OAC (n = 65) FFPE specimens were subjected to IHC staining for pRb, p16INK4A, cyclin D1, p53 and RNA in‐situ hybridization for E6/E7 transcripts. HPV DNA was determined via PCR in fresh frozen specimens. Viral load measurement (real‐time PCR) and Next Generation Sequencing of TP53 was performed. Of 218 patients, 56 were HPV DNA positive HPV16 (n = 42), 18 (n = 13), 6 (n = 1). Viral load was low. Transcriptionally active HPV (DNA+/RNA+) was only found in the dysplastic and adenocarcinoma group (n = 21). The majority of HPV DNA+/RNA+ BD/OAC were characterized by p
16highINK4A (14/21, 66.7%), pRblow (15/21, 71.4%) and p53low (20/21, 95%) and was significantly different to controls combination of HPV DNA–/RNA– (n = 94) and HPV DNA+/RNA– cohorts (n = 22). p53low had the strongest association with DNA+/RNA+ oesophageal lesions (OR = 23.5, 95% CI = 2.94–187.8, p = 0.0029). Seventeen HPV DNA+/RNA+ BD/OAC identified as p53low, were sequenced and all but one exhibited wild‐type status. pRblow/p53low provided the best balance of strength of association (OR = 8.0, 95% CI = 2.6–25.0, p = 0.0003) and sensitivity (71.4%)/specificity (71.6%) for DNA+/RNA+ BD/OAC. Active HPV involvement in BD/OAC is characterized by wild‐type p53 and aberrations of the retinoblastoma protein pathway.
What's new?
Active hr‐HPV involvement in BD/OAC is identified by a characteristic molecular signature consisting of retinoblastoma protein pathway alterations, that is, upregulation of p16INK4A, and downregulation of pRb as well as wild‐type p53. The transformation specific combination of p16high/pRblow, which is a feature of HPV driven lesions was identified in a significant proportion of virally positive BD/OAC. This data can be exploited for diagnostic, disease stratification, surveillance, and treatment (including vaccination) purposes of BD/OAC.
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