Is the mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin (ddTC) than to conventional taxane and carboplatin chemotherapy (TC) in high grade serous ovarian carcinoma? A survey of Japanese Gynecology Oncology Group study (JGOG3016A1).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5510-5510 ◽  
Author(s):  
Ryusuke Murakami ◽  
Noriomi Matsumura ◽  
Hiroshi Tanabe ◽  
Hirofumi Michimae ◽  
Mayu Yunokawa ◽  
...  
Keyword(s):  
Median Survival ◽  
High Grade ◽  
Oncology Group ◽  
Mesenchymal Transition ◽  
Pathological Classification ◽  
Pathological Subtype ◽  
Significant Difference ◽  
Gynecology Oncology ◽  
Dose Dense ◽  
Taxane Chemotherapy

5510 Background: High-grade serous ovarian cancer (HSOC) was divided into four transcriptome subtypes (i.e. Mesenchymal, Immunoreactive, Proliferative, and Differentiated). We established a new pathological classification based on these transcriptome subtypes: Mesenchymal Transition (MT) type, Immune Reactive (IR) type, Solid and Proliferative (SP) type and Papillo-Glandular (PG) type (PMID: 26993207). The MT type has the worst prognosis. We discovered the Mesenchymal transcriptome subtype might be sensitive to taxane chemotherapy. Therefore, we hypothesized that the MT type, which represents the Mesenchymal transcriptome subtype, may respond better to dose dense taxane combined with carboplatin (ddTC) rather than to conventional taxane and carboplatin (TC). Methods: We collected 207 HSOC slides registered in the Japanese Gynecology Oncology Group 3016 (JGOG3016) study. Two of the authors, R.M. and I.K., classified the samples into the four pathological subtypes (n=201). We categorized the patients into two groups based on the treatment they received: ddTC (n=95) or TC (n=106). Progression free survival (PFS) was compared between the two groups for each pathological subtype. Results: Among the MT patients, the ddTC group had a significantly better PFS than the TC group (n= 30 vs 42, median survival: 1.8 vs 1.2 years, p=0.01). Among the SP patients, the ddTC group had better PFS than the TC group, even though the difference was not statistically significant (n=22 vs 27, median survival: 3.2 vs 1.4 years, p=0.08). In contrast, among the IR patients, the two groups showed no significant difference in PFS (n=16 vs 16, median survival: 5.2 vs 5.8 years, p=0.64). The PG patients also showed no significant difference in PFS between the two groups (n=27 vs 21, median survival: 1.5 and 1.7 years, p=0.64). Conclusions: The HSOC of MT type is more responsive to ddTC than to TC. This new pathological classification reflecting HSOC transcriptome subtypes leads to individualization of chemotherapy treatments.

scholarly journals Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2699-2706 ◽  
Author(s):  
P Liu ◽  
T Leong ◽  
L Quam ◽  
D Billadeau ◽  
NE Kay ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Median Survival ◽  
Eastern Cooperative Oncology Group ◽  
Tumor Burden ◽  
Phase Iii ◽  
Oncology Group ◽  
Ras Mutation ◽  
Ras Mutations ◽  
Significant Difference

Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ras mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta 2-microglobulin levels, labelling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P ‼ .02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P ‼ .02). To determine if the status of ras mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ras mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-alpha showed statistically significant survival differences between mutant and wildtype ras status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wild-type ras had a median survival of 4.0 years (P ‼ .01).

Do Steroids Matter? A Retrospective Review of Premedication for Taxane Chemotherapy and Hypersensitivity Reactions

2021 ◽  
pp. JCO.21.01200
Author(s):  
Olivia M. Lansinger ◽  
Savanna Biedermann ◽  
Zihuai He ◽  
A. Dimitrios Colevas
Keyword(s):  
High Dose ◽  
High Grade ◽  
Hypersensitivity Reactions ◽  
Prescribing Practices ◽  
Cancer Group ◽  
Increased Risk ◽  
Gynecology Oncology ◽  
Group Sex ◽  
Taxane Chemotherapy ◽  
Manual Review

PURPOSE Despite the widespread use of the taxanes paclitaxel and docetaxel for a variety of cancers and their well-known association with hypersensitivity reactions (HSRs), there is still significant variation in the prescribing practices of steroids for premedication. Premedication almost always includes dexamethasone, which can be associated with multiple adverse effects if taken for extended periods of time. This study reviews the pattern of steroid premedication in patients who received paclitaxel or docetaxel at Stanford Cancer Institute between January 2010 and June 2020. METHODS We used an electronic query of the electronic medical record followed up with a manual review of patient charts to ask whether we could find a correlation between steroid premedication dosing and the incidence or severity of HSRs with the first taxane dose. Variables considered included steroid dose and route, dose and type of taxane, clinical cancer group, sex, and race. RESULTS Five thousand two hundred seventeen patients were identified as having received paclitaxel or docetaxel, and 3,181 met criteria for our analysis. There were 264 (8.3%) HSRs. In adjusted multivariate analysis, we found no correlation of HSR rate or severity among any of the variables evaluated except gynecology oncology clinic patients, who had an increased risk (hazard ratio [HR] 1.34) of HSRs overall and high-grade HSRs (HR 2.34), and female patients, who had a higher rate of HSRs overall (HR 1.26), but not high-grade HSRs. CONCLUSION Neither dexamethasone dose nor route correlated with subsequent HSRs. Given the potential for adverse events from repeated high-dose steroids, our findings suggest that routine use of lower doses, such as a single 10 mg dose of dexamethasone, as premedication for taxanes to prevent HSRs is preferable to the current prescribing guidelines.

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

scholarly journals How well do neurosurgeons predict survival in patients with high-grade glioma?

2021 ◽  
Author(s):  
Lisa Millgård Sagberg ◽  
Asgeir S. Jakola ◽  
Ingerid Reinertsen ◽  
Ole Solheim
Keyword(s):  
Median Survival ◽  
Survival Curve ◽  
Binary Logistic Regression ◽  
High Grade Glioma ◽  
Accurate Estimation ◽  
Binary Logistic Regression Analysis ◽  
High Grade ◽  
Clinical Prediction ◽  
Individual Level ◽  
Actual Survival

AbstractDue to the lack of reliable prognostic tools, prognostication and surgical decisions largely rely on the neurosurgeons’ clinical prediction skills. The aim of this study was to assess the accuracy of neurosurgeons’ prediction of survival in patients with high-grade glioma and explore factors possibly associated with accurate predictions. In a prospective single-center study, 199 patients who underwent surgery for high-grade glioma were included. After surgery, the operating surgeon predicted the patient’s survival using an ordinal prediction scale. A survival curve was used to visualize actual survival in groups based on this scale, and the accuracy of clinical prediction was assessed by comparing predicted and actual survival. To investigate factors possibly associated with accurate estimation, a binary logistic regression analysis was performed. The surgeons were able to differentiate between patients with different lengths of survival, and median survival fell within the predicted range in all groups with predicted survival < 24 months. In the group with predicted survival > 24 months, median survival was shorter than predicted. The overall accuracy of surgeons’ survival estimates was 41%, and over- and underestimations were done in 34% and 26%, respectively. Consultants were 3.4 times more likely to accurately predict survival compared to residents (p = 0.006). Our findings demonstrate that although especially experienced neurosurgeons have rather good predictive abilities when estimating survival in patients with high-grade glioma on the group level, they often miss on the individual level. Future prognostic tools should aim to beat the presented clinical prediction skills.

scholarly journals A descriptive analysis of end-of-life discussions for high-grade glioma patients

2021 ◽  
Author(s):  
Ai Chikada ◽  
Sayaka Takenouchi ◽  
Yoshiki Arakawa ◽  
Kazuko Nin
Keyword(s):  
End Of Life ◽  
Health Care Providers ◽  
Patient Participation ◽  
High Grade Glioma ◽  
Team Approach ◽  
High Grade ◽  
Care Providers ◽  
Patient Goals ◽  
Significant Difference ◽  
Eol Care

Abstract Background End-of-life discussions (EOLDs) in patients with high-grade glioma (HGG) have not been well described. Therefore, this study examined the appropriateness of timing and the extent of patient involvement in EOLDs and their impact on HGG patients. Methods A cross-sectional survey was conducted among 105 bereaved families of HGG patients at a university hospital in Japan between July and August 2019. Fisher’s exact test and the Wilcoxon rank-sum test were used to assess the association between patient participation in EOLDs and their outcomes. Results In total, 77 questionnaires were returned (response rate 73%), of which 20 respondents replied with refusal documents. Overall, 31/57 (54%) participated in EOLDs at least once in acute hospital settings, and a significant difference was observed between participating and nonparticipating groups in communicating the patient’s wishes for EOL care to the family (48% vs 8%, P = .001). Moreover, &gt;80% of respondents indicated that the initiation of EOLDs during the early diagnosis period with patients and families was appropriate. Most EOLDs were provided by neurosurgeons (96%), and other health care providers rarely participated. Additionally, patient goals and priorities were discussed in only 28% of the EOLDs. Patient participation in EOLDs was not associated with the quality of EOL care and a good death. Conclusions Although participation in EOLDs is relatively challenging for HGG patients, this study showed that participation in EOLDs may enable patients to express their wishes regarding EOL care. It is important to initiate EOLDs early on through an interdisciplinary team approach while respecting patient goals and priorities.

scholarly journals Impact of Extrahepatic Metastases on Overall Survival in Patients with Advanced Liver Dominant Hepatocellular Carcinoma: A Subanalysis of the SORAMIC Trial

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 771-786
Author(s):  
Kerstin Schütte ◽  
Regina Schinner ◽  
Mathias P. Fabritius ◽  
Melina Möller ◽  
Christiane Kuhl ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Median Survival ◽  
Pulmonary Metastases ◽  
Study Entry ◽  
Extrahepatic Disease ◽  
Advanced Hepatocellular Carcinoma ◽  
Significant Difference ◽  
Distant Organ ◽  
Extrahepatic Metastases ◽  
The Impact

<b><i>Introduction:</i></b> Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival. <b><i>Objective:</i></b> To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT). <b><i>Methods:</i></b> SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival. <b><i>Results:</i></b> In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, <i>n</i> = 11; adrenal glands, <i>n</i> = 5; peritoneum, <i>n</i> = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively (<i>p</i> = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; <i>p</i> = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, <i>p</i> = 0.0060). <b><i>Conclusions:</i></b> This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.

scholarly journals Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Disease Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

scholarly journals O39: THE HISTOPATHOLOGICAL AND MOLECULAR FEATURES OF BREAST CARCINOMA WITH HIGH-GRADE TUMOUR BUDDING

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
A Lloyd ◽  
E Ryan ◽  
M Boland ◽  
S Medani ◽  
Abd Elwahab ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Lymph Node Involvement ◽  
Low Grade ◽  
High Grade ◽  
Prognostic Variables ◽  
Mesenchymal Transition ◽  
Molecular Features ◽  
Newcastle Ottawa Scale ◽  
Tumour Budding

Abstract Background Tumour budding (TB) is an adverse histological feature in many cancers. It is thought to represent epithelial-to-mesenchymal transition, a key step in the metastatic process. The role of TB in breast carcinoma (BC) remains unclear. Aim To investigate the relationship between TB and other histological and molecular features of BC. Method A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Cochran–Mantel–Haenszel method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). Result Seven studies with a total of 1040 patients (high grade TB n=519, 49.9%; low grade TB n=521, 50.1%) were included. A moderate- to high-risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node involvement (OR 2.28, 95% c.i. 1.74 to 2.98, P&lt;0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P&lt;0.001). Regarding molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen- (OR 1.66, 95% c.i. 1.21 to 2.29, P=0.002) and progesterone-receptor positive (OR 1.68, 95% c.i. 1.10 to 2.59, P=0.02) tumours. In contrast triple negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P=0.0006). Conclusion High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC. Take-home message High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC.

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