Vaginal sarcoma: the Royal Marsden experience

Six patients with vaginal sarcoma are reported here. This clinicopathologic review confirms the poor prognosis of this disease. However, there were three 5-year survivors, all of whom had early stage disease and low to intermediate grade tumors. Apart from tumor grade, stage was of prognostic importance. Late recurrences at 5 and 21 years were noted in two of the three 5-year survivors. Neither chemotherapy nor radiotherapy were of use in the treatment of late stage or recurrent disease.

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The Prognostic Significance of Cytopenia in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL).

Blood ◽

10.1182/blood.v110.11.746.746 ◽

2007 ◽

Vol 110 (11) ◽

pp. 746-746

Author(s):

Clive S. Zent ◽

Wei Ding ◽

Karin F. Giordano ◽

Susan M. Schwager ◽

Tait D. Shanafelt ◽

...

Keyword(s):

Poor Prognosis ◽

Accurate Determination ◽

Prognostic Significance ◽

Lymphocytic Leukemia ◽

Clinical Staging ◽

Early Stage Disease ◽

Stage Disease ◽

Staging Systems ◽

Prognostic Importance ◽

Worse Prognosis

Abstract Background: Historically, CLL patients with cytopenia were thought to have a poor prognosis and cytopenia is a key feature of CLL clinical staging systems. The implications of cytopenia in CLL could have changed because of improved diagnostic accuracy, increased recognition of early stage disease, and better treatments. Newer data suggest that the etiology of cytopenia determines its prognostic importance in CLL. Patients with cytopenia caused by autoimmune disease (AID) are less likely to have the poor prognosis associated with patients with bone marrow (BM) failure. To determine the prognostic significance of cytopenia in patients with CLL, we performed an observational study at Mayo Clinic Rochester (MCR). Methods: We studied all patients with CLL seen in the Division of Hematology at MCR from 1 January 1995 to 31 December 2004 (n = 1,750). Cytopenia (hemoglobin < 10 g/dL or platelet count < 100 × 09/L) was considered due to BM failure in patients with extensive BM involvement by CLL (< 20% residual myeloid tissue on BM biopsy) or reticulocytopenia without other causes persisting > 3 months after CLL therapy. Cytopenia was attributed to AID in patients with autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red blood cell aplasia (PRCA), or autoimmune granulocytopenia (AIG). Results: Median age at diagnosis of CLL was 63.7 years (69% male). Cytopenia occured in 423 (24.2%) patients. In 303 patients, cytopenia was due to CLL (228 BM failure and 75 AID). In 120 patients cytopenia was due to CLL related factors (splenomegaly, n = 11; possible AID, n = 18; treatment of CLL, n = 16) or non CLL causes (other malignancy, n = 12; iron deficiency, n = 11; anemia of chronic disease, n = 10; renal failure, n = 6; drugs effect, n = 4; surgical blood loss n = 4). In 28 (6.6%) patients the cause of cytopenia was not definitively determined. Of the patients with BM failure, 97 (43%) had cytopenia at CLL diagnosis (70% male, median age 63.3 years [range 32–95]), The AID patients the median age of CLL diagnosis was 66.7 years (range 30–85) with 79% male. AID diagnoses were AIHA (n = 41), ITP (n= 35), PRCA (n=8), and AIG (n=3); 9 patients had > 1 AID. Survival from diagnosis of cytopenia was significantly better for patients with AID (median 9.1 years) than BM failure (median 4.4 years, p < 0.001). AID patients had a longer survival from diagnosis of CLL (median 12.4 years) versus the rest of the CLL population (median 9.5 years, p = 0.020) but patients with BM failure at diagnosis had a worse prognosis (median 6.2 years, p < 0.001). Conclusion: We show that the etiology of cytopenia in CLL patients determines its prognostic importance. Anemia and thrombocytopenia caused by BM failure, but not AID, are associated with a significantly worse prognosis. These data show the importance of accurate determination of the etiology of cytopenia in all patients with CLL. Cytopenia in patients with AID is not a marker of advanced stage disease; these patients often need different management compared to those with BM failure. Cytopenia due to AID versus BM failure can be difficult to distinguish and a BM study should be done in all patients considered for treatment. Patients with cytopenia due to AID cannot be meaningfully classified by current clinical staging systems. We believe that efforts to review the NCI-WG 96 criteria are timely and should consider the etiology of cytopenia in CLL patients.

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Frequency of late-stage breast cancer diagnoses despite high mammography screening rates in an HMO

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1526 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1526-1526

Author(s):

R. Haque ◽

J. E. Schottinger ◽

M. H. Kanter ◽

C. C. Avila ◽

R. Contreras ◽

...

Keyword(s):

Breast Cancer ◽

Late Stage ◽

Mammography Screening ◽

Early Stage ◽

Advanced Tumor Stage ◽

Early Stage Disease ◽

Advanced Tumor ◽

Stage Disease ◽

Late Stage Diagnosis ◽

The Impact

1526 Background: Kaiser Permanente Southern California (KPSC) led the nation in screening women for breast cancer (BCa) with a mammography rate of nearly 90% in 2007 according to 2008 Healthcare Effectiveness Data and Information Set (HEDIS) measures. Despite successes in improving screening rates in this health plan that serves 3+ million diverse members, the percentage of women diagnosed with late stage BCa (stage III, IV) remained stable, varying from 12.9% (N∼323) in 2003 to 10.8% (N∼270) in 2007. To identify patient and health care factors associated with late stage diagnosis and the impact of its enhanced screening implementation guidelines, KPSC undertook this study. Methods: This cross-sectional study included a cohort of 10,580 BCa patients from 2003–2007. We compared women diagnosed with late stage disease versus those with early stage disease (stages I, II). P values (2-sided) were based on the chi-square distribution. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. Results: Factors that were positively associated with late stage diagnosis in the univariate analyses included age, lack of recent mammography screening, worse tumor features, 80+ years of age, minority race, lower geocoded household income, increased healthcare visits, and use of Pap testing (P < 0.01 for all variables). Factors significantly associated with late stage diagnosis in the multivariate model included only lack of recent mammography screening (OR = 1.35, 95% CI: 1.14–1.58) and worse tumor features including high grade (grade 3, OR = 2.58, 95% CI: 1.96–3.40), positive lymph nodes (OR = 53.49, 95% CI: 39.90–71.72), and HER-2+ tumors (OR = 1.40, 95% CI: 1.13–1.72). Conclusions: Targeting older women, those with lower utilization, and women who did not have a recent mammogram may help further lower the prevalence of late stage diagnoses. However, given the extent of the health plan's previous efforts to enhance BCa screening rates, a ceiling effect may limit additional benefit. Additional efforts to decrease the rate of advanced tumor stage at diagnosis may include improving interpretation of mammograms or earlier detection of aggressive tumors by enhanced BRCA genetic testing. No significant financial relationships to disclose.

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Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽

10.1182/blood.v110.11.3056.3056 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3056-3056

Author(s):

B.E. Shaw ◽

N.P. Mayor ◽

A.-M. Little ◽

Nigel H. Russell ◽

A. Pagliuca ◽

...

Keyword(s):

Late Stage ◽

Early Stage ◽

Disease Stage ◽

Unrelated Donor ◽

Disease Relapse ◽

Early Stage Disease ◽

Hla Alleles ◽

Graft Versus Host ◽

Multiple Loci ◽

Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

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Molecular estimation of neurodegeneration pseudotime in older brains

Nature Communications ◽

10.1038/s41467-020-19622-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Sumit Mukherjee ◽

Laura Heath ◽

Christoph Preuss ◽

Suman Jayadev ◽

Gwenn A. Garden ◽

...

Keyword(s):

Late Stage ◽

Late Onset ◽

Early Stage ◽

Disease Onset ◽

Postmortem Brain ◽

Disease Stage ◽

Rna Seq ◽

Early Stage Disease ◽

Molecular Changes ◽

Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

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The Effect of Increasing Two-Week Wait Referrals for Head and Neck Cancer in East Kent

Bulletin of The Royal College of Surgeons of England ◽

10.1308/147363511x576164 ◽

2011 ◽

Vol 93 (6) ◽

pp. 217-220 ◽

Cited By ~ 4

Author(s):

S Haikel ◽

N Dawe ◽

G Lekakis ◽

M Black ◽

D Mitchell

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Late Stage ◽

Early Stage ◽

White Paper ◽

Early Stage Disease ◽

Stage Disease ◽

Late Stage Disease ◽

The Uk

In 1998 the UK government published its white paper The New NHS: Modern and Dependable, in which it first suggested that patients being referred with a suspicion of cancer should have a maximum wait of two weeks to see a specialist. The rationale for this was that outcomes for late-stage disease are significantly worse when compared with outcomes for early-stage disease (Table 1). It was assumed that reducing the wait to see a specialist would reduce the stage of disease at presentation.

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Treatment and Outcome of Patients with Uterine Carcinosarcoma in a Comprehensive Cancer Network

Indian Journal of Gynecologic Oncology ◽

10.1007/s40944-019-0362-6 ◽

2019 ◽

Vol 18 (1) ◽

Author(s):

K. Hapsari ◽

C. Bhugwandass ◽

G. W. J. van Rijn ◽

A. A. M. van der Wurff ◽

M. van ‘t Veer ◽

...

Keyword(s):

Surgical Treatment ◽

Adjuvant Chemotherapy ◽

Late Stage ◽

Adjuvant Radiotherapy ◽

Early Stage ◽

Uterine Carcinosarcoma ◽

Early Stage Disease ◽

Stage Disease ◽

Late Stage Disease ◽

Cancer Network

Abstract Aim To determine clinical characteristics, treatment modalities and survival of uterine carcinosarcoma (UCS). Methods Data on treatment of UCS patients in the Comprehensive Cancer Network south region in the Netherlands between 2004 and 2014 were retrospectively evaluated. Results Data of 62 patients with UCS were retrieved. Mean age at diagnosis was 69.2 years (45–95 years). Data of six patients were excluded because they did not receive any treatment. Of the 56 patients included in this study, 57.1% presented with early-stage (FIGO I–II) disease and 42.9% with late-stage (FIGO III–IV) disease. 46.9% of the patients with FIGO early-stage disease received only surgical treatment, whereas 9.4% received adjuvant chemotherapy and 43.8% received adjuvant radiotherapy. Median DFS in patients with early-stage disease was 47.0 months (17.5–72.0). Adjuvant therapy did not seem to alter prognosis (p = 0.261). 16.7% of the patients with late-stage disease received only surgical treatment, 12.5% received only chemotherapy, whereas 50% received adjuvant chemotherapy and 20.8% adjuvant radiotherapy after surgery. Median DFS in late-stage disease was 8.5 months (2.5–23.5). Adjuvant therapy did not seem to alter prognosis (p = 0.30). Conclusion UCS with both FIGO stages I–II and III–IV has a dismal prognosis. The addition of adjuvant treatment did not seem to increase survival.

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Specific TCR gene rearrangements in mycosis fungoides: does advanced clinical stage show a preference?

Journal of Clinical Pathology ◽

10.1136/jclinpath-2018-205324 ◽

2018 ◽

Vol 71 (12) ◽

pp. 1072-1077

Author(s):

Etan Marks ◽

Yanhua Wang ◽

Yang Shi ◽

Joseph Susa ◽

Mark Jacobson ◽

...

Keyword(s):

Mycosis Fungoides ◽

Late Stage ◽

Gene Rearrangement ◽

Early Stage ◽

Clinical Stage ◽

Disease Stage ◽

Gene Rearrangements ◽

Early Stage Disease ◽

Stage Disease ◽

Late Stage Disease

AimsThe relationship between the presence of specific T-cell receptor (TCR) gene rearrangements and clinical stage in mycosis fungoides (MF) has not been studied. We analysed a cohort of patients with a diagnosis of MF to determine the different types of specific TCR gene rearrangements present and their relationship to disease stage.MethodsA retrospective chart review was used to select patients with a diagnosis of MF who had a skin biopsy and a positive TCR gene rearrangement study in either blood or tissue and at least 2 years of clinical follow-up.Results43 patients were identified and divided into two groups. The first group consisted of 23 patients with early stage disease (IA-IIA) that was either stable or went into partial or complete remission with minimal intervention. None of these patients advanced to late stage disease. The second group consisted of 20 patients who had either late stage disease at diagnosis or progressed to late stage disease at some point in time. In the first group, only 4/23 (17%) patients had a single TCR gene rearrangement in the Vɣ1–8 region. In contrast, the second group had 13/20 (65%) patients with a single TCR gene rearrangement in the Vɣ1–8 region (p=0.002).ConclusionThe presence of a single TCR gene rearrangement in the Vɣ1–8 region could possibly be related to a more advanced stage of MF. However, more comprehensive studies, such as next generation sequencing, with a larger cohort is necessary for a more definitive conclusion.

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Antiangiogenic therapy for granulosa cell tumors of the ovary

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5574 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5574-5574

Author(s):

X. Tao ◽

A. K. Sood ◽

M. T. Deavers ◽

K. M. Schmeler ◽

A. M. Nick ◽

...

Keyword(s):

Overall Survival ◽

Granulosa Cell ◽

Recurrent Disease ◽

Early Stage ◽

Antiangiogenic Therapy ◽

Single Agent ◽

Prospective Trial ◽

Early Stage Disease ◽

Granulosa Cell Tumors ◽

Stage Disease

5574 Background: Sex-cord stromal ovarian tumors (SCSTs) tend to respond poorly to chemotherapy agents. Therefore, we examined the clinical efficacy of bevacizumab with or without concurrent chemotherapy and evaluated the angiogenic characteristics of these patients’ tumors. Methods: We conducted an IRB-approved retrospective review of all patients with SCSTs seen at our institution from February 2004 to October 2008. Eligible patients underwent pathologic confirmation and clinical evaluation, and received bevacizumab. VEGF and CD31 immunohistochemical staining (IHC) was performed when tissue was available; microvessel density (MVD) was measured based on CD31 counts. Results: We identified 8 eligible patients treated with bevacizumab. Of these, 7 had adult granulosa cell tumors (GCT) and one had a juvenile GCT. Of the 8 patients, 4 had early stage disease (I or II), 2 had advanced stage disease (III), and 2 were unstaged. All patients were treated for recurrent disease and had been previously treated with cytotoxic chemotherapy, with a median of 3.5 prior regimens (range, 1–6). Of the 8 patients, one patient had a complete clinical response, 2 patients had a partial response, 2 patients had stable disease, and 3 patients progressed, yielding a response rate of 38% and a clinical benefit rate of 63%. The median progression-free survival (PFS) was 7.2 months and the overall survival (OS) was not reached at a median follow-up after starting bevacizumab of 23.6 months. Of the 8 patients, 5 had tissue available for IHC. VEGF expression was noted at some level in all samples; overexpression was present in 1 of the 5 patients (upper tertile of score), and moderate expression was observed in 3 of the 5 patients (middle tertile). VEGF overexpression correlated with shorter PFS (p = 0.006) and shorter overall survival (p = 0.02). High MVD (>12.3 per previous data based on ROC analysis) was present in 3 of the 5 patients, and correlated with VEGF overexpression (p = 0.007) and shorter overall survival (p = 0.004). Conclusions: Anti-VEGF therapy is highly effective in patients with ovarian granulosa cell tumors. On the basis of these observations, a prospective trial has now been initiated using single agent bevacizumab in patients with recurrent disease. No significant financial relationships to disclose.

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Postoperative surveillance recommendations for early-stage colon cancer based on results from the clinical outcomes of surgical therapy trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4013 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4013-4013

Author(s):

V. L. Tsikitis ◽

K. Malireddy ◽

E. A. Green ◽

B. Christensen ◽

R. Whelan ◽

...

Keyword(s):

Colon Cancer ◽

Clinical Outcomes ◽

Surgical Therapy ◽

Late Stage ◽

Early Stage ◽

Early Stage Disease ◽

Postoperative Surveillance ◽

Stage Disease ◽

Therapy Trial ◽

Early Stage Colon Cancer

4013 Background: Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB & III) colon cancer. We hypothesized that stage I & IIA colon cancer patients would experience similar benefits. Methods: Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I & IIA; 537 patients) and late (stage IIB & III; 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. Results: Salvage rates for early and late stage disease patients with recurrence were the same (35.9% versus 37%, p=0.9 respectively). Median survival following second surgery after recurrence was 35.8 months late stage and 51.2 months for early stage patients respectively. Sites of first recurrence did not significantly differ between late and early stage disease: liver (37.4% vs. 27.2%); lung (29.7% vs.23.6%); intraabdominal (24.2% vs.10.9%); and locoregional (12.1% vs.10.9%). Methods of first detection of recurrence were also not significantly different: CEA (37.4% vs. 29.1%); CT scan (26.4% vs. 23.6%); chest X-ray (12.1% vs. 7.3%); and colonoscopy (8.8% vs. 12.7%), for late versus early stage disease, respectively. Conclusions: Patients with early stage colon cancer have similar sites of recurrence, and receive similar benefit from post-recurrence therapy as later stage patients; implementation of existing surveillance guidelines for early stage patients is appropriate. No significant financial relationships to disclose.

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Molecular estimation of neurodegeneration pseudotime in older brains

10.1101/686824 ◽

2019 ◽

Author(s):

Sumit Mukherjee ◽

Laura Heath ◽

Christoph Preuss ◽

Suman Jayadev ◽

Gwenn A. Garden ◽

...

Keyword(s):

Late Stage ◽

Protein Trafficking ◽

Early Stage ◽

Disease Onset ◽

Postmortem Brain ◽

Disease Stage ◽

Rna Seq ◽

Early Stage Disease ◽

Molecular Changes ◽

Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage – or disease pseudotime - for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0×10−5), Aβ (CERAD score, P = 1.8×10−5), and cognitive diagnosis (P = 3.5×10−7) of LOAD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

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