Change In Clinical Stage Research Articles

The impact of the COVID-19 pandemic on the diagnosis and treatment of breast cancer at a community hospital.

e18718 Background: COVID-19-related physical distancing restrictions impacted the delivery of close-contact healthcare care in the initial months of the pandemic. To ascertain the effect of these changes on breast cancer (BC) care at Gundersen Health System (GHS), we compared stage at diagnosis (dx), interval between dx and initiation of treatment (tx), and modality of first tx offered to pts (pts) diagnosed with BC before, during, and after pandemic-related restrictions. Methods: We performed a retrospective review of the electronic health records of approximately 904 pts with a new BC dx at GHS. Based on the timing of COVID-19-related restrictions at GHS, we designated any date from January 1, 2019 - March 31, 2020 as “Pre-COVID”, April 1, 2020 - December 31, 2020 as “COVID”, and January 1, 2021 - March 31, 2022 as “Post-COVID”. The median time to first tx for each modality of tx was compared using Kruskal-Wallis tests. Cox proportional hazard models were used to investigate patterns in the time to tx for various tx modalities in the three time periods of interest while accounting for clinical stage at dx. Changes in the distribution of modality of first tx, cancer stage at dx, type of surgery, and mode of disease detection across the three time periods of interest were assessed using Chi-square tests of association. Results: The median time to surgery for pts with surgery as first tx modality was significantly different between time periods (p < 0.001) with time to surgery shortest pre-COVID and longest post-COVID. Significant differences in time to first chemotherapy tx were noted for clinical stage 2 pts (p = 0.002), but not for pts diagnosed at other stages. No differences were noted in times to first hormone therapy tx (p = 0.28). There were significant differences in the distribution of modality of first tx (p < 0.001), the clinical stage at dx (p = 0.01), and the mode of detection (p = 0.04) across the three time periods. These differences reveal a shift in the typical paradigm of BC care due to the pandemic; with a delay in detection and tx, change in clinical stage at dx, and a change in the modality of the first tx. Conclusions: Our data illustrate the effect the pandemic had on routine BC care during and after the pandemic-related restrictions regarding time to first tx, clinical stage at the time of dx, and initial tx modality. Furthermore, these pandemic changes are ongoing with the time to first tx longer in the post-pandemic period as compared to pre-pandemic period. This delay in return to pre-pandemic standards may be due to continued issues with supply chain and staffing shortages. Identifying differences attributable to the pandemic will help guide future decisions regarding BC care should conditions necessitate the reimplementation of strict infection-prevention measures. Identifying issues that continue post-COVID will help determine strategies to close those care gaps.

Prospective Pilot Study of 18F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

BACKGROUND. PET/CT with 18F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. OBJECTIVE. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT. METHODS. This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT studies for abnormal uptake corresponding to known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that more than 60% of sites would have abnormal FES uptake, exceeding the percentage of ILC with abnormal FDG uptake described in prior literature. A sample size of 24 biopsied lesions was preselected to provide 81% power for the alternative hypothesis (one-sided α = .10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. RESULTS. The final analysis included 17 patients (mean age, 59.1 ± 13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22 of 25 (88%) lesions, sufficient to reject the null hypothesis (p = .002). Thirteen patients underwent FDG PET/CT. Four of 23 (17%) sites of histologically confirmed ILC, including additional sites detected and confirmed after enrollment, were identified with FES PET/CT only, and 1 of 23 (4%) was identified only with FDG PET/CT (p = .18). FES PET/CT depicted additional lesions not detected with standard-of-care evaluation in 4 of 17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). Use of FES PET/CT resulted in changes in clinical stage with respect to standard-of-care evaluation in 3 of 17 (18%) patients. CONCLUSION. The primary endpoint of the trial was met. The frequency of abnormal FES uptake among sites of histologically known ILC was found to be to be significantly greater than 60%. CLINICAL IMPACT. This pilot study shows a potential role of FES PET/CT in evaluation of patients with ILC. TRIAL REGISTRATION. ClinicalTrials.gov NCT04252859.

A longitudinal study evaluating interim assessment of neoadjuvant chemotherapy for bladder cancer.

To evaluate the usefulness of radiological re-staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re-staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC). We conducted a longitudinal, single-centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle-invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re-staging after two cycles of NAC and after completion of NAC before RC. Of 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25-0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC. Re-staging of muscle-invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re-staging after completion of NAC by CT is a strong predictor of overall survival.

The change of clinical stage after neoadjuvant chemotherapy in prediction of prognosis for borderline resectable and locally advanced pancreatic cancer

Response evaluation using computed tomography during neoadjuvant chemotherapy (NACT) is limited due to indistinct finding of fibrotic change around tumor. This study was aimed to investigate predictive role of change in clinical stage based on computed tomography (CT) during NACT n patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). BRPC and LAPC patients with NACT using FOLFIRINOX regimen were included between 2012 and 2019. The patients were divided into responsive, stationary, and aggravated groups based on the change of clinical stage in pre and post NACT CT images. We compared short and long term outcomes among three groups. Responsive, stationary, aggravated group were found in 37 (22.1%), 116 (69.4%), and 16 (9.5%) patients, respectively. Of 45 patients in pre-NACT stage III, 9 (20%) patients showed downward stage migration in responsive group and 25 (41.5%) patients were showed upward stage migration in 60 patients with pre-NACT stage I. Responsive group showed the better 3-year recurrence free survival rate compared with stationary and aggravated groups (44.2% vs. 23.5% vs. 0%; p = 0.001). Responsive group showed lower proportion of node metastasis (p = 0.048), lymphovascular invasion (p = 0.011) and smaller tumor size in pathology (p = 0.007) compared with other groups. Responsive group was associated with better recurrence free survival in FOLFIRINOX based NACT. And it may be helpful to manage the patients postoperatively for finding the characteristics of responsive group during NACT for BRPC and LAPC.

Evaluation of the AJCC Eighth-Edition Prognostic Staging System for Breast Cancer in a Latin American Cohort.

The staging of breast cancer has been based on tumor size, lymph node involvement, and presence or absence of distant metastases. The American Joint Committee on Cancer (AJCC) staging system in its eighth edition incorporates hormone receptors, human epidermal growth factor receptor 2 (HER2), and histologic grade due to their prognostic importance. In Latin America, however, the impact of the new edition is unknown. This article evaluates the performance of the AJCC eighth-edition staging system in a cohort of patients with breast cancer at a reference center in Colombia. The study investigated a descriptive cohort of 912 patients who received complete treatment for non-metastatic invasive breast cancer and had information on the anatomic stage and biologic factors,. All the patients were restaged using the AJCC eighth-edition classification. Changes in clinical stages and differences between the two classifications were compared. The study enrolled 912 patients. Changes in staging occurred for 54.82% (downstaging for 40.3% and upstaging for 14.47%) of these patients. For recurrence-free survival, the C-Index of the eighth-edition AJCC was 0.726, and the AIC was 1323.7, whereas the C-Index of the seventh-edition AJCC was 0.731, and the AIC was 1314.3 (p = 0.99). The seventh and eighth editions of the AJCC staging system have similar predictive values in our population for recurrence-free survival. Future studies are necessary to evaluate the performance of the AJCC eighth-edition staging system in predicting overall survival.

Chronic Lymphocytic Leukemia: Clinical Stages Maintain Their Prognostic Significance Over the Course of the Disease and Are Surrogates for Response to Therapy

BackgroundTo determine whether in patients with chronic lymphocytic leukemia (CLL), the clinical stage maintains prognostic significance over time and can be considered as a surrogate for the response to therapy. Patients and MethodsThe data from 229 CLL patients were retrospectively evaluated. The main aims of the study were to describe the changes in clinical stage during the course of CLL as a result of the response to treatment and to determine the time to next therapy (TTNT) and overall survival (OS) according to those changes, in particular, among the heterogeneous International Workshop on CLL (IWCLL) partial response (PR) category. ResultsAmong the patients in the IWCLL PR category, differences were found in TTNT and OS according to the clinical stage at the response evaluation. With a median follow-up period of 91 months (range, 2-390 months), patients with a PR- Binet A at the response evaluation had significantly longer TTNT and OS compared with those with PR-Binet B/C (median TTNT, 26 vs. 11 months; P = .00; median OS, 63 vs. 43 months; P = .047). ConclusionThe results of the present study have shown that for patients with CLL, the Binet clinical stages are good outcome predictors throughout the disease course and also suggest that changes in Binet clinical stage could be useful as response surrogates and to divide the IWCLL PR category into different prognostic subgroups.

Subspecialized radiology review at multidisciplinary pancreas conference: impact on patient management.

At our tertiary medical center, multidisciplinary subspecialists meet twice a week during a CME-accredited conference to discuss oncologic and non-oncologic patients with pancreatic diseases at which time a subspecialized abdominal staff radiologist reinterprets the patient's relevant imaging studies. This study assesses the changes in patient management due to imaging reinterpretation during multidisciplinary pancreas conference (MPC). In this retrospective, IRB-approved, HIPAA-compliant study, imaging studies of all patients discussed at MPC between July 1 and December 31, 2015 were assessed for technical adequacy, and original reports analyzed for congruency with reinterpretation. Management measures included change in diagnosis, clinical stage, treatment, or workup. Additional data were obtained on referring services affected and their resultant change in practice. Changes in surgical resectability, surgical approach, or delayed operative dates were noted for surgeons. Changes in chemotherapeutic or radiation oncology regimens as well as decisions for additional imaging, laboratory workup, or histologic evaluation were also recorded. A total of 252 patients were included (54.4% males, 45.6% females, mean age 63.71years). Relevant imaging consisted of 142 abdominal CT scans, 112 abdominal MRI scans, 1 abdominal ultrasound, and 1 nuclear medicine octreotide study of which 69.4% were performed in-house. Image quality was deemed appropriate in 95.2%. Cases presented included solid pancreatic malignancies (n = 140; 55.6%), cystic pancreatic lesions (n = 41; 16.3%), acute and chronic inflammatory conditions (n = 52; 20.6%), and miscellaneous entities (n = 10; 4.0%); 9 (3.6%) cases were normal. Image reinterpretation was congruent with original reports in 56.7%, with minor, moderate, and major discrepancies occurring in 9.5, 26.2%, and 7.5% of cases, respectively. Incongruent reinterpretation was predominantly due to perceptional errors (false-negative reports due to missed findings) and interpretative errors (false-positive results due to over-reporting or misclassification of diagnoses). Services most commonly affected included surgical oncology, radiology, and gastroenterology at 16.7%, 13.1%, and 12.7% of cases, respectively. Management changes included a change in diagnosis in 8.7%, change in clinical stage in 8.7%, change in treatment in 17.9%, and further workup needed in 19.0% of patients, respectively. No change in management occurred in the remaining 61.5% of cases. Subspecialized abdominal radiologist reinterpretation in the context of more comprehensive patient information heavily impacts the multidisciplinary management of patients with pancreatic disorders. Further efforts are needed to solidify the abdominal radiologist's role in the multidisciplinary clinical setting.

Efficacy versus Complications in Arterial Thrombolysis

Acute peripheral arterial occlusions threaten life and limb. Thrombolysis is an established, minimally invasive alternative treatment for surgical thromboembolectomy. Yet, there is no consensus regarding an optimal thrombolysis protocol, and current knowledge is largely based on studies from the 1990s. This study reviews a contemporary cohort of patients treated with thrombolysis and aims to evaluate the treatment results and to identify possible predictors for outcome and (bleeding) complications. The electronic health record data of all consecutive patients who underwent thrombolysis for acute limb ischemia due to thromboembolic lower extremity arterial occlusions between April 2006 and June 2012 were analyzed. End points were change in clinical stage of ischemia, incidence of bleeding complications, duration of thrombolysis, predictors of outcome and complications, and mortality and amputation-free rates after 30-day and 6-months follow-up. In total, 109 cases were included. Clinical improvement was observed in 79%. Amputation-free rates at 30 days and 6months were 94% and 90%, respectively. The incidence of major bleeding complications was 13%. Median duration of thrombolysis was 27 (4-68) hr. Mortality rates at 30 days and 6 months were 7% and 16%, respectively; none bleeding related. In addition to age, popliteal artery occlusions and a progressed chronic vascular stage are predictive for a worse outcome. Age, female sex, and cardiac history were risk factors for bleeding. Treatment of peripheral arterial occlusions with high-dose thrombolysis on an intensive-care unit yields high clinical success rates, but major bleeding complications are often observed. Strict clinical observation remains essential since intensive monitoring of hemostatic parameters during thrombolysis does not predict bleeding complications.

Changes in Clinical Stage Identify Different Response Categories Among Patients in Iwcll PR: Analysis of CLL Patients on the Resonate Study

Background:In CLL/SLL, the iwCLL PR category is heterogeneous and complex to evaluate. Changes in clinical staging (Binet, Rai) have been proposed as a method to evaluate response in CLL (Montserrat, Cancer 1985; iwCLL, Ann Intern Med 1989). Ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the FDA for the treatment of pts with CLL/SLL and allows for treatment without chemotherapy. Robust improvements in progression-free survival (PFS) and overall survival (OS) among ibr-treated pts in the phase 3 RESONATE trial demonstrated superiority of ibr over ofatumumab (ofa) in heavily pretreated CLL, regardless of prognostic features. As the majority of ibr pts achieved iwCLL PR or PR-L manifested by improved hematologic function and/or disease burden, we analyzed RESONATE pts with PR or PR-L by Binet stage to determine if clinical downstaging captures different, clinically meaningful subgroups among patients in iwCLL PR/PR-L.Methods:Among 391 previously treated CLL pts randomized to receive oral ibr (n=195) or intravenous ofa (n=196), those who achieved a best overall response of PR or PR-L were assessed for Binet Stage at time of first response. Stage A was defined as no anemia or thrombocytopenia and <3/5 sites of involvement (unilateral or bilateral cervical, axillary, and inguinal lymph nodes, liver, spleen); Stage B as no anemia or thrombocytopenia and ≥3/5 involved sites; and Stage C as anemia (hemoglobin <10 g/dL) and/or thrombocytopenia (platelets <100,000/µL) regardless of lymph node/organ site involvement. Binet stage data were considered missing if any one component of the staging criteria was not available. Kaplan-Meier analyses were performed based on Binet Stage at time of first response. Data were analyzed as of the interim analysis (Byrd, N Engl J Med 2014), and p-values are descriptive.Results:A total of 162 (83%) ibr pts and 45 (23%) ofa pts achieved PR/PR-L as best overall response as assessed by investigator; 53% of ibr responders were PR and 46% were PR-L at first response. Baseline characteristics (age, prior therapy, marrow infiltration, unmutated IGHV) were balanced between arms. A majority of PR/PR-L ibr pts were downstaged to Stage A reflecting improvement in lymphadenopathy/organomegaly and/or cytopenias with treatment. At time of first PR/PR-L, the proportion of Stage C pts decreased from 44% (n=72) at baseline to 27% (n=44) for the ibr arm and from 42% (n=19) to 33% (n=15) for the ofa arm. While maintaining PR/PR-L, 48% of ibr-treated and 40% of ofa-treated pts shifted from Stage C to A (or to B/A). The efficacy of ibr over ofa in PR/PR-L pts was similar to that observed in the intent-to-treat population for median PFS (not reached [NR] for ibr vs. 8.48 mo for ofa, P<0.0001). A treatment effect between ibr vs. ofa was also observed for duration of response (DOR) in PR/PR-L pts (NR for ibr vs. 5.52 mo for ofa, P<0.0001). Responders with PR/Stage A showed a longer PFS outcome than responders with PR/Stage C at time of first response to ibr (P=0.0314, Figure). The estimated median PFS for Stage C should be interpreted with caution as it occurred at the tail end of the curve with 2 pts at risk. Within the ofa arm, no difference in PFS between PR/Stage A vs. PR/Stage C was observed, although a limited sample size of responders prohibits robust analysis of this arm. For the ibr arm, both OS (P=0.0281) and DOR (P=0.0431) suggest a trend for improved outcome for PR/Stage A vs. PR/Stage C. Subset analysis (e.g., pts with del17p; PR vs PR-L outcomes) were not feasible because of the small number of pts in these categories.Conclusions:This ad-hoc analysis shows that changes in clinical stage break down the PR/PR-L (iwCLL) category into different, clinically meaningful subgroups, and reinforces the notion that improving cytopenias is a desirable goal of CLL therapy with ibrutinib (Barrientos, ASH 2014). Altogether, this study demonstrates that changes in clinical stage could be a useful and non-costly method to evaluate treatment response at different time points over the course of the disease, a concept with potential clinical implications that requires validation in prospective clinical trials. [Display omitted] DisclosuresDelgado:Janssen: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Suzuki:AbbVie: Equity Ownership; Pharmacyclics, LLC, an Abbie Company: Employment, Other: Leadership, travel, accommodations, expenses. Hsu:AbbVie: Equity Ownership; Pharmacyclics, LLC, an Abbie Company: Employment. James:Pharmacyclics, LLC, an AbbVie Company: Employment; AbbVie: Equity Ownership. Montserrat:Vivia Biotech: Equity Ownership; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses; Morphosys: Other: Expert Testimony; Gilead: Consultancy, Other: Expert Testimony.

MP09-09 HISTORICAL TRENDS IN HIGH-RISK PROSTATE CANCER PATIENTS CHARACTERISTICS: A 27 YEARS OLD OBSERVATIONAL STUDY FROM A MULTICENTER PROSTATE CANCER CLINICAL AND TRANSLATIONAL RESEARCH GROUP

MP09-09 HISTORICAL TRENDS IN HIGH-RISK PROSTATE CANCER PATIENTS CHARACTERISTICS: A 27 YEARS OLD OBSERVATIONAL STUDY FROM A MULTICENTER PROSTATE CANCER CLINICAL AND TRANSLATIONAL RESEARCH GROUP

Sonography and Sonographically Guided Needle Biopsy of Internal Mammary Nodes in Staging of Patients With Breast Cancer.

The purpose of this study was to identify the prevalence of occult nodal metastases on routine ultrasound examination of internal mammary (IM) nodal basins in patients with breast cancer. Patients with primary breast cancer (n = 595) underwent breast ultrasound evaluation between September 1, 2011, and April 1, 2012. For all patients, ultrasound examination included a survey of the axillary, infraclavicular, IM, and supraclavicular nodal basins. Patient demographics, breast cancer histopathologic type, and grade, size, location, and presence of metastatic nodes in regional nodal basins were recorded. Fisher exact test and Wilcoxon rank test were used for statistical analysis. Fifty-eight of 595 (10%) patients had positive IM ultrasound finding, with eight (1.3%) patients having isolated IM involvement. Patients with positive IM ultrasound findings were statistically significantly younger than those without such findings (median age, 42 vs 57 years; p < 0.0001). Of the 58 patients with positive IM ultrasound, 29 (50%) underwent ultrasound-guided needle biopsy, which confirmed malignancy in 26 of 29 (90%) patients. Nonlateral (p < 0.001) grade 3 (p < 0.001) tumors larger than 5 cm (p < 0.0006) with the estrogen receptor-negative HER2/neu-negative subtype (p < 0.001) associated with axillary, infraclavicular, or supraclavicular metastases (p < 0.001) were more likely to be associated with positive IM ultrasound findings. IM ultrasound resulted in an N status change for 46 of 595 (8%) patients and of the overall clinical stage for 38 (6.4%) patients. IM ultrasound and ultrasound-guided fine-needle aspiration biopsy are feasible, sensitive, and specific. Application of IM ultrasound and ultrasound-guided needle biopsy in a selected subpopulation of young patients with medial or central estrogen receptor-negative HER2/neu-negative breast cancer may result in a change in clinical stage and modify the treatment plan.

Active surveillance for prostate cancer: when to recommend delayed intervention.

There are no agreed upon guidelines for placing patients on active surveillance (AS). Therefore, there are no absolute criteria for taking patients off AS and when to recommend treatment. The criteria used to define progression are currently based on prostate specific antigen (PSA) kinetics, biopsy reclassification, and change in clinical stage. Multiple studies have evaluated predictors of progression such as PSA, PSA density (PSAD), prostate volume, core positivity, and visible lesion on multiparametric magnetic resonance imaging (mpMRI). Furthermore, published nomograms designed to predict indolent prostate cancer do not perform well when used to predict progression. Newer biomarkers have also not performed well to predict progression. These findings highlight that clinical and pathologic variables are not enough to identify patients that will progress while on AS. In the future, with the use of imaging, biomarkers, and gene expression assays, we should be better equipped to diagnose/stage prostate cancer and to distinguish between insignificant and significant disease.

FDG-Positron Emission Tomography in T-Cell Lymphoma

Abstract 1614 Background:Few data are available on the role of fluoro-deoxy-glucose positron emission tomography (FDG-PET) in T-cell non Hodgkin Lymphoma (NHL). We compared standard contrast-enhanced computerized tomography (CECT) and FDG-PET for initial staging and restaging after treatment in T-cell NHL. Methods:We reviewed 58 FDG-PET scans performed in 29 patients (pts) affected by T-cell NHL and we focused on the 42 cases for which a simultaneous standard CECT was available for comparison. The specific T-cell histology was Peripheral T-Cell Lymphoma Not Otherwise Specified in 12 pts, Angioimmunoblastic T-Cell Lymphoma in 4 pts, Anaplastic Large Cell Lymphoma in 10 pts, other T-NHL hystologies in 3 pts. Twelve pts were males and median age at diagnosis was 57 years (range: 25–77). Baseline FDG-PET scans were 20, while FDG-PET performed for disease reassessment were 22. Results:FDG-PET performed at baseline was positive in all cases. In 6 cases (30%) FDG-PET identified fewer disease sites than CECT, while in 14 cases (70%) FDG-PET identified additional disease sites. New sites identified by FDG-PET were: other nodal sites (11 pts), spleen (2 pts), nasopharynx (1 pt) and testicles (1 pt). Different disease extent evaluation according to FDG-PET modified clinical stage in 10 pts (50%): one pt was downstaged and 9 pts were upstaged. FDG-PET-based stage was not considered for therapeutic decision. FDG-PET scans performed at restaging were negative in 16 cases (72%) and positive in the remaining 6 cases (28%). In 13/16 (81%) negative cases CECT was concordant and showed a complete remission, while in the remaining 3 cases CECT showed a residual nodal disease. In the 6 FDG-PET positive cases, CECT was as follows: abnormal in the same site of FDG-PET in 1 case, abnormal in fewer sites than FDG-PET in 3 cases and abnormal in more sites than FDG-PET in 2 cases. With a median follow-up of 32 months, the median overall survival (OS) of the 6 positive FDG-PET cases at restaging was 26 months. With a median follow-up of 23 months, the median OS of the 16 negative FDG-PET cases at restaging was not reached. Conclusion:FDG-PET can be useful in the initial staging of T-cell NHL, since it can allow a more accurate disease extension evaluation: in our experience it could identify additional sites, both nodal and extra-nodal, in 70% of pts. A change in clinical stage according to FDG-PET was observed in 50% of cases, with an upstaging in the majority of pts. We could confirm the high sensitivity of baseline FDG-PET in T-cell NHL. A high level of concordance was observed between PET and CECT at restaging. However, independently on CECT result, the worse OS of FDG-PET positive cases confirms the role of FDG-PET as prognostic factor for survival. Larger prospective trials are needed to confirm the utility of FDG-PET in baseline staging, reassessment after chemotherapy and treatment planning. Disclosures:No relevant conflicts of interest to declare.

Comparison analysis of Chinese 2008, 1992 and 2002 UICC staging system for nasopharyngeal carcinoma

Objective To compare the Chinese 2008, 1992 and 2002 UICC (International Union Against Cancer) staging System for nasopharyngeal carcinoma and find out the reasons for the changes in the new Chinese 2008 staging system. Methods From Apr. 2007 to Dec. 2008, 285 naive patients with pathologically proved NPC, but without metastasis, received standard enhanced MRI scans of the nasopharynx and neck. Based on MRI imaging data and clinical information, clinical stage was classified according to the Chinese 2008, Chinese 1992 staging system and 2002 6th UICC staging system,respectively. Comparisons were made between Chinese 2008 and 1992 staging system, and between Chinese 2008 and 2002 UICC staging system by χ2 test. Results As a result of deleting some details of the old staging system, Chinese 2008 staging system is easier to grasp. With Chinese 2008 staging system, the number of cases in stage T1 to T4 are 66, 84, 72,63, respectively; those in stage N0 to N3 are 12,48,169,56; the number of cases in clinical stage Ⅰ -Ⅳ are 5,30,141 and 109. With 2002 6th UICC staging system, the number of cases in stage T1 to T4 are 66, 83, 55,81; those in stage N0 to N3 are 26,50,201,8;the number of cases in clinical stage Ⅰ -Ⅳ are 6,40,153 and 86. With Chinese 1992 staging system, the number of cases in stage T1 to T4 are 62,91,71,61; those in stage No to N3 are 26,189,61,9; the number of cases in clinical stage Ⅰ -Ⅳ are 6, 110, 98 and 71. Comparing with the staging results of Chinese 1992 staging system, many cases showed different stage based on Chinese 2008 system including 12 cases (4.21%) inT stage (3 up-staging and 9 down-staging), 217 cases (76.14%) in N stage (216 up-staging, most rise I stage, and 1 down-staging), 123 cases (43. 16% ) in clinical stage ( 121 up-staging and 2 down-staging). Comparing with the staging results of 2002 UICC staging system, 35 cases ( 12. 28% )changes in T stage (8 up-staging and 27 down-staging), 77 cases (27. 02% ) changes in N stage (all upstaging, most rise 1 stage), 74 cases (25. 95% ) changes in clinical stage (54 up-staging and 20 downstaging) based on Chinese 2008. Comparing the constituent ratio of T, N and clinical staging results separately, statistical differences were found between Chinese 2008 and Chinese 1992 staging system in N0,N1, N2, N3, clinical stage Ⅱ , Ⅲ, Ⅳ. Statistical difference was also found in N0, N2, N3, clinical stage Ⅳ between Chinese 2008 and 2002 UICC staging system. χ2 test results show that there is N0 significant difference of T stage constituent ratio among the 3 staging system ( χ2 = 6. 916, P = 0. 329 ), but the difference of N stage and clinical stage constituent ratio are significant( χ2 = 275. 169 and 84. 515, P ＜0. 0125). Conclusion Chinese 2008 Staging System for nasopharyngeal carcinoma is based on MRI, with clear definition to some anatomical location, after deleting some details in the old stage system, it's easier to use. The most obvious change for Chinese 2008 Staging System is the up-staging in N staging,which leads to the changes in clinical stage and constituent ratio of stage result. Key words: Nasopharyngeal neoplasms; Neoplasm staging; Magnetic resonance imaging

Molecular and Biological Characterization of Equine Infectious Anemia Virus Rev

Equine infectious anemia virus (EIAV) is one of the most divergent members of the lentivirus subfamily of retroviruses and is considered a useful comparative model for molecular studies of lentivirus replication. The Rev protein of EIAV is functionally homologous with other lentiviral Revs and facilitates export of incompletely spliced viral mRNAs through a Crm1-dependent pathway. The trans- and cis-acting elements that mediate EIAV Rev function are similar to, but distinct from, the well-characterized elements in human immunodeficiency virus (HIV-1), the prototypical Rev protein. In addition, the EIAV rev sequence is highly variable in vivo, and changes in Rev phenotype correlate with changes in clinical stages of EIAV infection. This review summarizes the molecular biology of EIAV Rev-RRE interactions and the consequences of Rev variation in vivo. A comparative perspective of Rev activity may enhance understanding of an essential lentiviral protein and stimulate new strategies for treatment and prevention of lentivirus infections in vivo.

PET for staging of Hodgkin's disease and non-Hodgkin's lymphoma.

Metabolic or molecular imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has emerged as a powerful imaging modality for diagnosis, staging, and therapy monitoring of a variety of cancers. The accuracy of FDG-PET as an imaging tool for the primary staging of lymphoma suffers from the absence of a reference criterion to which all imaging modalities can be compared. For ethical reasons, pathological diagnosis is usually not possible for all of the lesions and abnormalities found. In this article, the current state of the art for staging of primary lymphoma is reviewed and the implications for staging and the impact on patient management discussed. Whole-body PET using FDG is superior to conventional staging, i.e., physical examination, laboratory tests, plain radiography, and CT, by 10-20%. The sensitivity of FDG-PET varies for different regions of the body and appears lowest for infradiaphragmatic disease involvement. Staging with metabolic imaging leads in 10-40% of patients to a change in clinical stage. Highly variable results have been reported on whether up- or downstaging of lymphoma with PET leads to changes in the therapeutic approach for primary lymphoma.

Prognostic value of the lymphocyte doubling time in chronic lymphocytic leukemia.

The prognostic value of lymphocyte doubling time (LDT), expressed in months and obtained by means of a linear regression, has been studied in 99 previously untreated chronic lymphocytic leukemia (CLL) patients. LDT is defined as the period of time needed for lymphocytes to double in number the amount found at diagnosis. When the analysis was extended to the whole population, it showed clear differences in the life expectancy of patients with LDT of less than or equal to 12 months (median survival, 36 months; relative death rate [O/E]1.57) compared with those with LDT of more than 12 months (median survival not yet reached; O/E, 0.37) (P less than 0.001). The significance of LDT remained even after adjustments were made for age, sex, lymphocyte count, anemia, and thrombocytopenia. The lack of statistical significance after adjustment for Binet's clinical stage corresponds to the fact that clinical stages are not distributed homogeneously, high LDT being more frequently associated with earlier stages and low LDT with more advanced forms of the disease (P less than 0.001). In this study LDT was a useful parameter in predicting disease progression. Patients in Stages A and B and with rapidly increasing lymphocytes counts became worse more frequently (33.3% and 29.1%, respectively, at 12 months after diagnosis) than those with a slow increase (no change in clinical stage at 12 months). It is concluded that since LDT appears to predict the progression of the disease, it is useful in the clinical management of CLL.

Evaluation of carcinoembryonic antigen, tissue polypeptide antigen, placental alkaline phosphatase, and modified nucleosides as biological markers in malignant lymphomas.

We have evaluated CEA, TPA, PLAP in sera from patients with three different kinds of malignant lymphomas. Six modified nucleosides, psi, m1A, m1G, m1I, m2G, and m2(2)G were analyzed in the urine from the same group of patients. The histological diagnoses were histiocytic lymphoma (21 patients), lymphocytic lymphoma (19 patients) and Hodgkin's disease (23 patients). The patients were classified into four different clinical stages. Consecutive samples were analyzed before and during ongoing radiotherapy and chemotherapy and during the post-treatment period. Our results showed that TPA and PLAP had limited value as biological markers for patients with malignant lymphomas. For CEA a possible correlation with clinical stage was observed only in patients with Hodgkin's disease. The modified nucleosides, especially psi, showed a correlation with clinical stage for patients with all three diagnoses. Elevated levels of psi in urine were in healthy adults 4%, in patients in clinical stage 1 14%, and in patients with advanced disease 62%. Six cases showed a good correlation between the change in clinical stage upon treatment and the parallel change in the level of psi in the urine. Our results suggest that modified nucleosides, especially psi, are valuable as biological markers for patients with malignant lymphomas.

Value of preoperative evaluation in patients with lymphoma.

The records of 136 patients with Hodgkin's lymphoma and of 32 patients with non-Hodgkin's lymphoma who underwent staging laparotomy were reviewed. There were changes in the clinical stage of 25% of the patients after laparotomy. Forty-one percent of the lymphangiograms and 55% of the liver-spleen scintiscans were inaccurate or nondiagnostic. There were few stage alterations by laparotomy in patients in clinical stages I and II. There was a higher frequency of stage changes in clinical stage III1 and III2 patients. Staging laparotomy is not recommended for clinical stages I and II but is mandatory for stages III1 and III2.