Moving from late to early stage disease: lessons learned from erlotinib in pancreatic cancer

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.

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Circulating Cell-Free Tumour DNA for Early Detection of Pancreatic Cancer

Cancers ◽

10.3390/cancers12123704 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3704

Author(s):

Jedrzej J. Jaworski ◽

Robert D. Morgan ◽

Shivan Sivakumar

Keyword(s):

Pancreatic Cancer ◽

Early Detection ◽

Early Stage ◽

Lower Sensitivity ◽

Detection Rates ◽

Early Stage Disease ◽

Genetic Sequencing ◽

Number Of Factors ◽

Stage Disease ◽

Invasive Method

Pancreatic cancer is a lethal disease, with mortality rates negatively associated with the stage at which the disease is detected. Early detection is therefore critical to improving survival outcomes. A recent focus of research for early detection is the use of circulating cell-free tumour DNA (ctDNA). The detection of ctDNA offers potential as a relatively non-invasive method of diagnosing pancreatic cancer by using genetic sequencing technology to detect tumour-specific mutational signatures in blood samples before symptoms manifest. These technologies are limited by a number of factors that lower sensitivity and specificity, including low levels of detectable ctDNA in early stage disease and contamination with non-cancer circulating cell-free DNA. However, genetic and epigenetic analysis of ctDNA in combination with other standard diagnostic tests may improve early detection rates. In this review, we evaluate the genetic and epigenetic methods under investigation in diagnosing pancreatic cancer and provide a perspective for future developments.

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Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.349 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 349-349

Author(s):

Heather Stuart ◽

Caroline Ripat ◽

Basem Azab ◽

Danny Yakoub ◽

Dido Franceschi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Stage ◽

Clinical Stage ◽

Stage I ◽

Clinical Staging ◽

Early Stage Disease ◽

Risk Of Mortality ◽

Stage Disease ◽

Pathologic Staging ◽

Group 2

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p < 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p < 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p < 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

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COLLISION TUMORS OF THE CERVIX IN AN EARLY STAGE DISEASE. A CASE REPORT

10.26226/morressier.5770e29ad462b80290b4b9f3 ◽

2016 ◽

Author(s):

Jimmy Billod

Keyword(s):

Case Report ◽

Early Stage ◽

Early Stage Disease ◽

Collision Tumors ◽

Stage Disease

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Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

BJU International ◽

10.1111/j.1464-410x.2011.10870.x ◽

2012 ◽

Vol 109 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Michael Marberger ◽

Jelle Barentsz ◽

Mark Emberton ◽

Jonas Hugosson ◽

Stacy Loeb ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

Early Stage Disease ◽

Prostate Cancer Diagnosis ◽

Diagnosis And Management ◽

Stage Disease ◽

Novel Approaches ◽

Improve Prostate Cancer

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Surgery in Small-Cell Lung Cancer

Cancers ◽

10.3390/cancers13030390 ◽

2021 ◽

Vol 13 (3) ◽

pp. 390

Author(s):

Nicola Martucci ◽

Alessandro Morabito ◽

Antonello La Rocca ◽

Giuseppe De Luca ◽

Rossella De Cecio ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Stage I ◽

Phase Iii ◽

Small Cell Lung ◽

Early Stage Disease ◽

Stage Disease

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.

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Female Breast Cancer in Suriname: Pathways to Treatment—A Patient’s Perception

JCO Global Oncology ◽

10.1200/go.20.45000 ◽

2020 ◽

Vol 6 (Supplement_1) ◽

pp. 49-49

Author(s):

Euridice R. Irving ◽

Dennis R. A. Mans ◽

Els Th. M. Dams ◽

Maureen Y. Lichtveld

Keyword(s):

Breast Cancer ◽

Health Care ◽

Access To Health Care ◽

Early Stage ◽

Diagnosis And Treatment ◽

Related Factors ◽

Entire Interval ◽

Early Stage Disease ◽

Resource Setting ◽

Stage Disease

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.

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SP-0156 Early stage disease, adjuvant treatment including molecular risk classification

Radiotherapy and Oncology ◽

10.1016/s0167-8140(21)08516-9 ◽

2021 ◽

Vol 161 ◽

pp. S96

Author(s):

C. Creutzberg

Keyword(s):

Adjuvant Treatment ◽

Early Stage ◽

Risk Classification ◽

Early Stage Disease ◽

Stage Disease

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Elevated Breast Cancer Mortality in Women Younger than Age 40 Years Compared with Older Women Is Attributed to Poorer Survival in Early-Stage Disease

Breast Diseases A Year Book Quarterly ◽

10.1016/s1043-321x(09)79403-2 ◽

2009 ◽

Vol 20 (4) ◽

pp. 371-372

Author(s):

M.A. Chung

Keyword(s):

Breast Cancer ◽

Older Women ◽

Cancer Mortality ◽

Early Stage ◽

Breast Cancer Mortality ◽

Early Stage Disease ◽

Stage Disease

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Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?

Hematology ◽

10.1182/asheducation-2013.1.406 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 406-413 ◽

Cited By ~ 9

Author(s):

Michelle Fanale

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Radiation Treatment ◽

Early Stage ◽

B Cell Lymphoma ◽

B Cell Lymphomas ◽

Early Stage Disease ◽

Stage Disease ◽

Relapsed Disease

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.

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