scholarly journals Transcriptomic Profiles Differentiate Normal Rectal Epithelium and Adenocarcinoma

2015 ◽  
Vol 100 (5) ◽  
pp. 818-826 ◽  
Author(s):  
J. Hogan ◽  
K. Dejulius ◽  
X. Liu ◽  
J. C. Coffey ◽  
M. F. Kalady

Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation to retain only highly dysregulated genes. Genes differentially expressed between cancer and normal tissue on two-groups t test (P < 0.05, Bonferroni P value adjustment) were further analyzed. Genes were rank ordered in terms of descending fold change. For each comparison (tumor versus normal epithelium), those 5 genes with the greatest positive fold change were grouped in a classifier. Five separate tests were applied to evaluate the discriminatory capacity of each classifier. Genetic classifiers derived comparing normal epithelium with malignant rectal epithelium from pooled stages had a mean sensitivity and specificity of 99.6% and 98.2%, respectively. The classifiers derived from comparing normal and stage I cancer had comparable mean sensitivities and specificities (97% and 98%, respectively). Areas under the summary receiver-operator characteristic curves for each classifier were 0.981 and 0.972, respectively. One gene was common to both classifiers. Classifiers were tested in an independent Gene Expression Omnibus–derived dataset. Both classifiers retained their predictive properties. Transcriptomic profiles comprising as few as 5 genes are highly accurate in differentiating normal from adenocarcinomatous rectal epithelium, including early-stage disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 813-813 ◽  
Author(s):  
Christophe Ferme ◽  
Marine Diviné ◽  
Andrej Vranovsky ◽  
Frank Morschhauser ◽  
Réda Bouabdallah ◽  
...  

Abstract The aim of the trial was to compare three modalities of chemotherapy and involved-field radiotherapy (IF-RT) in adult patients with supradiaphragmatic CS I-II HL with risk factors. Patients were randomized if they presented with age ≥ 50, or CS II4–5, or A + ESR ≥ 50, or B + ESR ≥ 30, or MT ratio ≥ 0.35. The trial compared ABVD x 6 cycles and IF-RT (36–40 Gy) vs ABVD x 4 cycles and IF-RT vs BEACOPP baseline x 4 cycles and IF-RT. From October 1998 to September 2002, 808 patients were enrolled in 111 institutions from 10 European countries. The proportions of grade 3–4 chemotherapy-related hematological toxicity (mainly WBC) were 74%, 70% and 63%, respectively; That of grade 1–3 RT-related hematological toxicity were 10%, 12% and 17%, respectively. Ten (2+3+5, 1%) patients stopped chemotherapy because of toxicity and 8 (2+2+4, 1%) refused the treatment; Six (2+2+2, 1%) patients stopped radiotherapy because of toxicity and 9 (3+1+5, 1%) refused the treatment. The proportions of patients in CR/CRu were 74%, 71% and 59% after 6, 4 ABVD and 4 BEACOPP, respectively. After a median follow-up of 57 months (range 33–81), 78 events (26 progressions, 37 relapses, 15 deaths) were observed. At July 2005, the 4-year event-free survival (EFS) and overall survival (OS) rates are as follows: Treatment No. Pts CR-CRu /PR /NC-PD 4-yr EFS 4-yr OS 6 ABVD + IF-RT 276 87% /8% /5% 91% 95% 4 ABVD + IF-RT 277 86% /11% /3% 87% 94% 4 BEACOPP + IF-RT 255 84% /12% /4% 90% 93% P value 0.607 0.380 0.978 Overall, 42 patients have died of progressive disease (5, 7 and 7 patients), treatment-related complication (7, 5 and 2), intercurrent disease (1, 0 and 2), second malignancy (1 NHL, 0 and 1 AML) or cause unspecified (0, 3 and 1). These preliminary results indicate that a combination of 4 cycles of ABVD and IF-RT is sufficient to cure a large majority of HL patients with unfavorable early stage disease and that BEACOPP baseline has no advantage over ABVD in these patients.


ESMO Open ◽  
2019 ◽  
Vol 4 (6) ◽  
pp. e000559
Author(s):  
Jun Hao Lim ◽  
Santhanam Sundar

Background Small cell carcinoma of the urinary bladder (SCCB) is an extremely rare malignancy which is often associated with poor survival outcome. Literature reporting such disease is scarce. There is no standardised management. This retrospective audit examines a UK Cancer Centre’s SCCB management and survival outcomes.Methods Histopathology database at Nottingham University Hospitals, UK, was used to identify patients diagnosed with SCCB from January 2008 to January 2016.Results 27 patients had confirmed diagnosis of SCCB. Mean age at diagnosis was 68.7 (range 37–90). 30% of the cases had pure small cell histology, while the rest were mixed histological subtype. Of the 12 patients with early stage disease (stage I and II), three had radical cystectomy and chemotherapy, six had both radiotherapy and chemotherapy, two had either radiotherapy or chemotherapy alone, and one declined active treatment. Of the 12 patients with advanced disease (stage III and IV), four had chemotherapy alone, four had both radiotherapy and chemotherapy and four was for best supportive care. 13 out of 16 patients who had chemotherapy received combination of carboplatin and etoposide. Patients with advanced stage disease had medial survival of 9 months (95% CI 3.9 to 14.1 months). The median survival for patients with early disease was not reached. There is significant difference in survival between early and late stage disease (p value 0.008, Log rank test).Conclusions Our results demonstrated a reasonable survival outcome in early stage SCCB patients. Radical multimodality treatment options should not be precluded in patients with early stage SCCB.


2012 ◽  
Vol 109 ◽  
pp. 1-7 ◽  
Author(s):  
Michael Marberger ◽  
Jelle Barentsz ◽  
Mark Emberton ◽  
Jonas Hugosson ◽  
Stacy Loeb ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.


2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 49-49
Author(s):  
Euridice R. Irving ◽  
Dennis R. A. Mans ◽  
Els Th. M. Dams ◽  
Maureen Y. Lichtveld

PURPOSE Delays across the entire cancer care continuum are not uncommon. This cross-sectional study explored the health care trajectories of Surinamese women with breast cancer and identified predictors of timely diagnosis and treatment initiation. METHODS One hundred women age 30 years or older who were newly diagnosed with breast cancer in 2017 to 2018 were recruited from all 4 hospitals in Paramaribo. Data on their demographics, lifestyle, reproductive and medical history, health status, and family history of breast cancer and other malignancies were collected using a validated semistructured questionnaire. Using Anderson’s Model of Pathways to Treatment, we defined a patient interval (from detection to first consultation), diagnostic interval (from consultation to histopathologic diagnosis), and treatment interval (from diagnosis to first treatment). Log-transformed data were analyzed using linear regression, and variables with P ≤ .05 were considered statistically significant predictors of intervals. RESULTS All participants had health insurance and access to health care. Eighty-five percent of patients presented with early-stage disease. Ninety percent of patients had self-detected their disease, with 70% finding a lump. Average age was 55.6 years (± 11.8 years). Median durations of patient, diagnostic, and treatment intervals were 13 days (interquartile, range, 4-63 days), 40 days (IQR, 21-57 days), and 18 days (IQR, 8-38 days), respectively. Median duration of the entire interval was 95 days (IQR, 59-272 days). Patient-related factors associated with the intervals were religion (β = −530; P = .003), being employed (β = 149.4; P = .007), and age 50 years and older (β = −195.8; P = .037). Disease-related factors were lump as first symptom (β = −175.6; P = .038) and late-stage disease at diagnosis (β = 213.5; P = .004). CONCLUSION Given the limited-resource setting, delays in Suriname’s health care can be minimized by programs aimed at increasing breast cancer awareness and education; however, delays may have been underestimated as a result of the over-representation of early-stage disease and recall bias regarding the first symptom detected.


Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 406-413 ◽  
Author(s):  
Michelle Fanale

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic entity, with only ∼ 500 new cases in the United States per year with a similar infrequent incidence worldwide. NLPHL also has distinctive pathobiology and clinical characteristics compared with the more common classical Hodgkin lymphoma (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic cells and an overall more indolent course with a higher likelihood of delayed relapses. Given the limited numbers of prospective NLPHL-focused trials, management algorithms historically have typically been centered on retrospective data with guidelines often adopted from cHL and indolent B-cell lymphoma treatment approaches. Key recent publications have delineated that NLPHL has a higher level of pathological overlap with cHL and the aggressive B-cell lymphomas than with indolent B-cell lymphomas. Over the past decade, there has been a series of NLPHL publications that evaluated the role of rituximab in the frontline and relapsed setting, described the relative incidence of transformation to aggressive B-cell lymphomas, weighed the benefit of addition of chemotherapy to radiation treatment for patients with early-stage disease, considered what should be the preferred chemotherapy regimen for advanced-stage disease, and even assessed the potential role of autologous stem cell transplantation for the management of relapsed disease. General themes within the consensus guidelines include the role for radiation treatment as a monotherapy for early-stage disease, the value of large B-cell lymphoma–directed regimens for transformed disease, the utility of rituximab for treatment of relapsed disease, and, in the pediatric setting, the role of surgical management alone for patients with early-stage disease.


2014 ◽  
Vol 14 (1) ◽  
pp. 70-79 ◽  
Author(s):  
A. Hutchinson ◽  
P. Bridge

AbstractPurposeTo establish whether the use of a passive or active technique of planning target volume (PTV) definition and treatment methods for non-small cell lung cancer (NSCLC) deliver the most effective results. This literature review assesses the advantages and disadvantages in recent studies of each, while assessing the validity of the two approaches for planning and treatment.MethodsA systematic review of literature focusing on the planning and treatment of radiation therapy to NSCLC tumours. Different approaches which have been published in recent articles are subjected to critical appraisal in order to determine their relative efficacy.ResultsFree-breathing (FB) is the optimal method to perform planning scans for patients and departments, as it involves no significant increase in cost, workload or education. Maximum intensity projection (MIP) is the fastest form of delineation, however it is noted to be less accurate than the ten-phase overlap approach for computed tomography (CT). Although gating has proven to reduce margins and facilitate sparing of organs at risk, treatment times can be longer and planning time can be as much as 15 times higher for intensity modulated radiation therapy (IMRT). This raises issues with patient comfort and stabilisation, impacting on the chance of geometric miss. Stereotactic treatments can take up to 3 hours to treat, along with increases in planning and treatment, as well as the additional hardware, software and training required.ConclusionFour-dimensional computed tomography (4DCT) is superior to 3DCT, with the passive FB approach for PTV delineation and treatment optimal. Departments should use a combination of MIP with visual confirmation ensuring coverage for stage 1 disease. Stages 2–3 should be delineated using ten-phases overlaid. Stereotactic and gated treatments for early stage disease should be used accordingly; FB-IMRT is optimal for latter stage disease.


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