The Clinical Usefulness of Novel Prognostic Factors in CLL: A Study of 477 Patients with Low-Risk (Non-11q, Non-17p) FISH and Known IGVH Mutation Status.

Abstract In order to develop integrated models utilizing commonly available prognostic factors, we studied the clinical signficance of IGVH mutation, CD38 and ZAP-70 in 477 CLL patients (pts) with low-risk (non-11q, non-17p) FISH findings. All pts were untreated at the time of FISH assessment, and were collected prospectively in the MD Anderson CLL database. Two hundred & fifteen pts (45%) had mono- (n=160) or bi-alleleic (n=55) deletion of 13q {DEL13Q}, 162 pts (34%) had a negative FISH panel {NEG}, and 100 pts (21%) had trisomy 12 as sole FISH abnormality (n=78) or in association with deletion 13q (n=22) {T12}. Compared to other FISH groups, DEL13Q pts had lower B2m (median 2.2 v 2.6mg/L, p=0.01) and were less likely to be IGVH unmutated (33% v 48%, p=0.001). In contrast, T12 pts were more likely to present with advanced stage disease (Rai≥2 36% v 23%, p=0.01), be CD38 positive (44% v 13%, p<0.001), and have karyotypic abnormalities (48% v 7%, p<0.001). One hundred and twenty-three pts had active disease requiring immediate therapy and 354 pts had stable disease, of whom 291 were evaluable for disease progression. At a median follow-up of 20 months, 73 pts had developed active disease with NCI-WG indication(s) for treatment. Actuarial 2 year time to treatment (TTT) was 26%, with no significant difference between 13q, NEG and T12 pts (p=0.27). TTT was associated with elevated B2m (≥1.5ULN), IGVH mutation status and ZAP-70 in DEL13Q and NEG pts, but not in T12 patients (Table). For DEL13Q/NEG pts, a simple model using IGVH mutation and B2m separated high risk pts (unmutated or high B2m, 2yr TTT 43%) from standard risk pts (mutated and low B2m, 2yr TTT 11%, p<0.0001). For T12 pts, a model based on CD38 positivity and karyotypic abnormalities separated high risk pts (2 factors, 2yr TTT 75%) from standard risk pts (0 or 1 factor, 2yr TTT 15%, p=0.008). These results show that the impact of prognostic factors on TTT is dependent on the underlying FISH karyotype, and underscores the need for future studies in CLL prognostic factors to take into account the complete risk profile of the pt. NEGATIVE FISH DELETION 13Q TRISOMY 12 p-value hazard ratio p-value hazard ratio p-value hazard ratio IGVH Mutation <0.001 8.0 0.003 2.9 0.97 0.98 B2m ≥1.5ULN <0.001 4.5 0.07 2.2 0.54 0.68 CD38 Positivity 0.05 2.5 0.05 2.4 0.06 7.4 Abn Cytogenetics <0.001 11.0 0.27 2.2 0.09 2.8 ZAP-70 0.02 2.9 0.007 3.1 0.70 1.3 Figure Figure Figure Figure

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P23 MALNUTRITION INDICES AS PROGNOSTIC FACTORS FOR POSTOPERATIVE COMPLICATIONS IN ESOPHAGEAL CANCER PATIENTS

Diseases of the Esophagus ◽

10.1093/dote/doz092.23 ◽

2019 ◽

Vol 32 (Supplement_2) ◽

Author(s):

Lidoriki Irene ◽

Schizas Dimitrios ◽

Mpaili Efstratia ◽

Mpoura Maria ◽

Hasemaki Natasha ◽

...

Keyword(s):

Esophageal Cancer ◽

Prognostic Factors ◽

High Risk ◽

Postoperative Complications ◽

Anastomotic Leakage ◽

Cancer Patients ◽

Preoperative Assessment ◽

Low Risk ◽

Major Complications ◽

The Impact

Abstract Aim To investigate the impact of malnutrition on postoperative complications in esophageal cancer patients. Background and Methods Malnutrition is common in esophageal cancer patients due to the debilitating nature of their disease. Several methods of nutritional assessment have emerged as significant prognostic factors for short-and long-term outcomes in patients operated for esophageal cancer. The study sample consisted of 85 patients with esophageal (n=11) and gastroesophageal junction (n=74) cancer who were admitted for surgery in the First Department of Surgery, Laikon General Hospital, Athens, Greece, between September 2015 and March 2019. Out of them, 65 patients underwent esophagectomy, while 20 patients underwent total gastrectomy. The assessment of nutritional status included the Geriatric Nutritional Risk Index (GNRI), the Patient Generated Subjective Global Assessment (PG-SGA) and sarcopenia. GNRI was based on preoperative values of patients’ serum albumin and body weight. The preoperative assessment of sarcopenia was based on Skeletal Muscle Index (SMI) derived from analysis of CT scans using SliceOmatic® Software version 4.3 (Tomovision, Montreal, Canada). Postoperative complications were graded according to Clavien-Dindo classification. Minor complications included categories I-II, whereas major complications included categories III-V. Results Thirty nine patients (47.6%) developed postoperative complications. More specifically, 21 patients (24.7%) developed minor complications and 18 patients (21.2%) developed major complications, while anastomotic leakage occurred in 10 patients (11.8%). Eighty patients (94.1%) had a high-risk GNRI (<92), while 5 patients (5.9%) had a low-risk GNRI (≥92). Forty four patients (51.8%) were diagnosed with sarcopenia. The mean PG-SGA score was 8.82 ± 5.57. Patients with a high-risk GNRI demonstrated significantly higher rate of overall complications compared to low-risk GNRI patients (100% vs 44.2%, p<0.05 respectively). Moreover, the rate of anastomotic leakage was significantly higher in the sarcopenia group than in the non-sarcopenia group (29% vs 3.4%, p<0.05). Nonetheless, PG-SGA was not significantly associated with postoperative outcomes. Conclusion Higher-risk scores on the GNRI are associated with an increased risk for developing postoperative complications, while sarcopenia is associated with higher risk for anastomotic leakage among esophageal cancer patients. Preoperative assessment of GNRI and sarcopenia should be performed in all patients in order to detect patients who are at greater risk of postoperative morbidity.

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High Expression of the Very Late Antigen (VLA)-4 (CD49d) Integrin Predicts for Reduced Risk of Relapse and Better Outcome in Pediatric Acute Myeloid Leukemia (AML): A Report From the Children's Oncology Group.

Blood ◽

10.1182/blood.v114.22.1592.1592 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1592-1592

Author(s):

Walter B. Walter ◽

Todd A. Alonzo ◽

Robert B. Gerbing ◽

Franklin O. Smith ◽

Susana C. Raimondi ◽

...

Keyword(s):

High Risk ◽

Clinical Outcome ◽

Risk Classification ◽

Low Risk ◽

Significant Heterogeneity ◽

Oncology Group ◽

Monosomy 7 ◽

Entire Cohort ◽

The Impact ◽

Standard Risk

Abstract Abstract 1592 Poster Board I-618 Background Previous studies highlighted the importance of the cell adhesion molecule, VLA-4, for chemoresistance and minimal residual disease (MRD) in AML, suggesting promise as therapeutic target. By comparison, the prognostic role of VLA-4 in AML remains controversial with retrospective studies implying either adverse or favorable prognosis. Therefore, we prospectively evaluated VLA-4 expression in participants of a recent Children's Oncology Group (COG) AML pilot protocol. Methods COG-AAML03P1 enrolled 340 newly diagnosed children (aged 1 month - 21 years) with de novo non-acute promyelocytic AML, excluding those with Down syndrome, and tested the feasibility of combining gemtuzumab ozogamicin (GO) with intensive induction chemotherapy followed by GO-containing intensification therapy or matched related donor stem cell transplantation; 216 patients submitted diagnostic marrow specimens for flow cytometric determination of VLA-4 expression that was then correlated with patient demographics, laboratory characteristics, and clinical outcome. Cytogenetics and molecular prognostic markers were used for risk classification as follows: low risk (mutation in core-binding factor, NPM1, or CEBPa; n=73), high risk (-5/5q-, monosomy 7, or FLT3/ITD with high allelic ratio; n=25), or standard risk (all other patients with cytogenetic/molecular data; n=101); 17 patients had insufficient data for risk classification. Results Among the 216 diagnostic specimens, the mean fluorescence intensity (MFI) of VLA-4 expression varied over 35-fold from a baseline of 30 to 1110 (median, 219.5). Patients with high VLA-expression (>median MFI) were younger (p<0.001), had a lower prevalence of FLT3/ITD (p=0.002). Presence of extramedullary disease (EMD, chloroma or CNS involvement) was significantly higher in patients with high VLA-4 expression (16% vs. 5%, p=0.013), where 17/22 (77%) of patients with EMD had high VLA-4 expression. We initially inquired whether VLA-4 expression as a continuous variable correlated with disease outcome. We demonstrated that over the range of VLA-4 expression levels, every 10-unit increase in VLA-4 MFI corresponded to a 2% decrease in relapse risk (RR; p=0.023) and 2% increase in disease-free survival (DFS) from end of induction I (p=0.015). We subsequently divided the study patients into two cohorts based on median MFI and determined the clinical outcome per median VLA-4 MFI for the entire cohort as well as in specific risk groups (i.e., high risk, low risk, and standard risk). In the evaluation of the entire cohort, patients with high VLA-4 expression had a significantly superior DFS (67% vs 48%, p=0.023) and lower RR (24% vs 44%, p=0.011) compared to those with lower VLA-4 expression. In subgroup analyses, high VLA-4 expression was associated with significantly superior DFS (69% vs 34%, p=0.011) and lower RR (26% vs 61%, p=0.009) in patients with standard-risk AML but not in patients with high or low risk disease. In multivariate Cox regression analyses that included age, cytogenetics, and molecular prognostic factors, low VLA-4 expression remained significantly associated with elevated RR (hazard ratio for low VLA-4: 2.25, p=0.011). Finally, we determined the impact of MRD in the context of VLA-4 expression. The prevalence of MRD was similar for patients with low or high VLA-4 expression (29% vs. 25%, p=0.70). In patients with low VLA-4 expression, those with MRD had a RR of 75% compared to that of 35% for the MRD negative cohort (p=0.005). Corresponding DFS was 19% and 54% for those with and without MRD (p=0.018), a difference mainly attributable to increased RR. In patients with high VLA-4 expression, those with MRD had a RR of 31% vs. 23% for the MRD-negative patients (p=0.28) with a corresponding DFS of 46% and 75% for the MRD positive and negative patients (p=0.014), a difference mainly explained by higher treatment-related mortality in MRD positive patients. Conclusion This study demonstrates significant heterogeneity of VLA-4 expression in pediatric AML and its association with EMD and clinical outcome. This study further demonstrates that VLA-4 expression is an independent prognostic factor for clinical outcome and can identify the risk status in patients with no identifiable cytogenetic or molecular risk factors. Disclosures No relevant conflicts of interest to declare.

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Select High Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy with Fludarabine and Rituximab in Chronic Lymphocytic Leukemia (CLL): Preliminary Justification for Risk-Adapted Therapy.

Blood ◽

10.1182/blood.v104.11.476.476 ◽

2004 ◽

Vol 104 (11) ◽

pp. 476-476 ◽

Cited By ~ 1

Author(s):

John C. Byrd ◽

John G. Gribben ◽

Bercedis Peterson ◽

Michael R. Grever ◽

Gerard Lozanski ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Hierarchical Classification ◽

P53 Mutation ◽

Low Risk ◽

P Value ◽

P53 Mutations ◽

Cytogenetic Abnormalities ◽

Mutational Status ◽

Risk Patients

Abstract Several prognostic factors in CLL including un-mutated VH mutational status, select interphase cytogenetic abnormalities [del(11q22.3), del(17p13.1)], and p53 mutations have been associated with decreased time from diagnosis to symptomatic disease requiring treatment as well as shortened progression-free survival (PFS) and overall survival (OS). To date, the impacts of these prognostic factors on treatment outcome with fludarabine and rituximab combination treatments have not been explored. The Cancer and Leukemia Group B recently reported results of a randomized phase II study (CALGB 9712) that added rituximab concurrently or sequentially to fludarabine as initial therapy for symptomatic, untreated CLL (Blood2003; 101:6). After a recently updated median follow-up of 43 months, PFS and OS are still similar in both arms. Of the 104 patients enrolled, we studied 88 patients for whom pre-treatment samples were available to examine the impact of VH mutational status (≥97% defined as un-mutated), common cytogenetic abnormalities, and p53 mutational status on outcome relative to CR (complete remission) and PFS. OS was not examined because only 13 deaths have occurred to date. A total of 46 out of 75 (61%) patients were VH un-mutated CLL. Fifteen (52%) of 29 mutated and 20 (43%) of 46 un-mutated patients achieved a CR (p= 0.49). The median PFS among the VH mutated patients was 46 months [95% CI (40, 54)] whereas for un-mutated it was 32 months [95% CI (22, 42)] (p= 0.05). Controlling for differences in age, sex, WBC, LDH, and stage resulted in an adjusted p-value of p=0.03. Only four patients had p53 mutations, preventing analysis of this biologic feature independently. Using the Dohner hierarchical classification, the frequency CR rate and PFS for each group are summarized below. Cytogenetic Abnormality: del(17p) del(11q) del(6q) tris 12 del(13q) Normal No. (%) pts 3 (3%) 15 (17%) 1 (1%) 23 (26%) 24 (27%) 22 (25%) CR (%) 0 53 100 25 38 64 PFS (months) 18 25 42 42 45 49 Using the hierarchical classification of Dohner, there was not a difference in CR rate (p=0.25) and PFS (p=0.10). Controlling for differences in age, sex, WBC, LDH, and stage resulted in an adjusted p-value of p=0.04. The PFS for the del(17p13.1) and del(11q22.3) patients was significantly shorter than that observed for the remaining cytogenetic groups (p=0.03). We next sought to define a high-risk group of CLL patients, as having any of the following: VH un-mutated (≥97%), del(17p), del (11q), or non-silent p53 mutation. Using this classification, 35 patients were assigned to the low-risk and 53 to the high-risk groups. The CR rate in each group was 43%. However, the median PFS among the low risk patients was 45 months with 95% CI (45, NA) whereas the median PFS among the high-risk patients was 32 months with 95% CI (22, 42) (p=0.004). These data demonstrate that high risk CLL patients characterized by VH un-mutated (≥97%), del(17p), del (11q), or non-silent p53 mutation appear to have a shorter PFS with chemoimmunotherapy and define a subset of patients for whom additional novel treatment approaches should be targeted.

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ZAP-70 Protein Retains Its Prognostic Significance within Interphase Cytogenetic Groups in B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Blood ◽

10.1182/blood.v104.11.2806.2806 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2806-2806

Author(s):

Maria Ilaria Del Principe ◽

Giovanni Del Poeta ◽

Maria Christina Cox ◽

Paola Panetta ◽

Luca Maurillo ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

B Cell ◽

Prognostic Significance ◽

Normal Karyotype ◽

Hazard Ratio ◽

Poor Risk ◽

Therapeutic Decisions ◽

Trisomy 12 ◽

The Impact

Abstract Heterogeneous clinical behavior of B-CLL makes difficult for physicians to identify which pts experience a slowly progressive clinical course and which ones may benefit from an early and/or more aggressive treatment. The development of interphase FISH techniques allowed to detect selected chromosome abnormalities in non-dividing cells. In 325 CLL pts, multivariate analysis identified 17p- and 11q- abnormalities as variables associated with shorter overall survival (OS) (Dohner, 2000). Moreover, the lack of IgVH gene mutation has been shown to predict a rapid disease progression (DP) and an inferior OS (Damle, Hamblin, 1999). B-CLL cells that use non-mutated IgVH genes express ZAP-70 protein, associated with an enhanced B cell receptor signaling and with an early DP risk. The aims of our study were: 1) to determine progression-free survival (PFS) and OS upon cytogenetic groups and ZAP-70 expression; 2) whether ZAP-70 could predict varied outcome within interphase cytogenetic groups; and 3) whether ZAP-70 and interphase cytogenetic groups were independent prognostic factors. We investigated 216 pts, median age 64 years, 69 pts belonging to low Rai stage, 140 to intermediate stage and 7 to high stage. To date, we have completed analysis of interphase cytogenetics in 137 pts, and ZAP-70 was quantified in 216 pts by a multicolor flow cytometric method using a cut-off value of 20%. With regard to cytogenetic groups, 73 (53.3%) pts had a normal karyotype and 35 (25.5%) pts had 13q-. Twenty-nine (21.2%) pts with trisomy 12, 17p- and 11q- were pooled together and defined as “poor-risk” cytogenetic subset. ZAP-70+ pts were 81/216 (37.5%) and there was a significant correlation between high or low ZAP-70 expression and Ig V gene mutational status (P<0.00001) in 125 examined CLL pts. Furthermore, we found significant associations either between higher ZAP-70 and trisomy 12, 17p-, 11q- or lower ZAP-70 and normal karyotype (P=0.0002). With regard to clinical outcome, a shorter PFS was observed in ZAP-70+ pts (13% vs 57% at 12 years; P<0.00001) and in “poor risk” cytogenetic pts vs normal karyotype pts (9% vs 49% at 12 years; P=0.008). The 13q- pts showed an intermediate outcome (23% at 12 years). ZAP-70+ pts showed also a shorter OS (24% vs 92% at 14 years; P=0.0002). To further explore the impact of ZAP-70 among cytogenetic groups, we investigated its expression within the normal karyotype and “poor risk” CLL subsets. As a matter of fact, ZAP-70 positivity was associated both with a shorter DFS and OS in normal karyotype (16% vs 62% at 10 years, P=0.002 and 69% vs 91% at 10 years, P=0.02, respectively) and in “poor risk” pts pooled together with 13q- pts (0% vs 35% at 13 years, P=0.0017 and 24% vs 100% at 14 years, P=0.03, respectively). In multivariate analysis of PFS, only ZAP-70 (hazard ratio=6.1, P=0.01) and soluble CD23 (hazard ratio=3.9, P=0.04) resulted to be independent prognostic factors. In conclusion, ZAP-70 expression predicts significantly both DFS and OS, and varies by interphase cytogenetic group. Within normal karyotype and poor risk cytogenetic subsets, where progression is heterogeneous, ZAP-70 positivity is able to distinguish pts who have early PFS or short OS. Therefore, ZAP-70 adds prognostic information to cytogenetic data and will assist in planning therapeutic decisions for CLL pts.

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Modified STOP-Bang for predicting perioperative adverse events in the Thai population

BMC Anesthesiology ◽

10.1186/s12871-021-01347-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lisa Sangkum ◽

Chama Wathanavaha ◽

Visasiri Tantrakul ◽

Munthana Pothong ◽

Cherdkiat Karnjanarachata

Keyword(s):

High Risk ◽

Adverse Events ◽

Oxygen Therapy ◽

Elective Surgery ◽

Low Risk ◽

Perioperative Outcomes ◽

P Value ◽

Icu Admission ◽

Obstructive Sleep ◽

Postanesthetic Care Unit

Abstract Background Undiagnosed obstructive sleep apnea (OSA) is associated with adverse perioperative outcomes. The STOP-Bang questionnaire is a validated screening tool for OSA. However, its precision may vary among different populations. This study determined the association between high-risk OSA based on the modified STOP-Bang questionnaire and perioperative adverse events. Methods This cross-sectional study included patients undergoing elective surgery from December 2018 to February 2019. The modified STOP-Bang questionnaire includes a history of Snoring, daytime Tiredness, Observed apnea, high blood Pressure, Body mass index > 30 kg/m2, Age > 50, Neck circumference > 40 cm, and male Gender. High risk for OSA was considered as a score ≥ 3. Results Overall, 400 patients were included, and 18.3% of patients experienced perioperative adverse events. On the basis of modified STOP-Bang, the incidence of perioperative adverse events was 23.2 and 13.8% in patients with high risk and low risk (P-value 0.016) (Original STOP-Bang: high risk 22.5% vs. low risk 14.7%, P-value 0.043). Neither modified nor original STOP-Bang was associated with perioperative adverse events (adjusted OR 1.91 (95% CI 0.99–3.66), P-value 0.055) vs. 1.69 (95%CI, 0.89–3.21), P-value 0.106). Modified STOP-Bang ≥3 could predict the incidence of difficult ventilation, laryngoscopic view ≥3, need for oxygen therapy during discharge from postanesthetic care unit and ICU admission. Conclusions Neither modified nor original STOP-Bang was significantly associated with perioperative adverse events. However, a modified STOP-Bang ≥3 can help identify patients at risk of difficult airway, need for oxygen therapy, and ICU admission. Trial registrations This study was registered on Thai Clinical Trials Registry, identifier TCTR20181129001, registered 23 November 2018 (Prospectively registered).

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TissueCypher Barrett’s esophagus assay impacts clinical decisions in the management of patients with Barrett’s esophagus

Endoscopy International Open ◽

10.1055/a-1326-1533 ◽

2021 ◽

Vol 09 (03) ◽

pp. E348-E355

Author(s):

David L. Diehl ◽

Harshit S. Khara ◽

Nasir Akhtar ◽

Rebecca J. Critchley-Thorne

Keyword(s):

High Risk ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Clinical Decision Making ◽

Eradication Therapy ◽

Low Risk ◽

Management Approach ◽

Low Grade ◽

Management Decisions ◽

The Impact

Abstract Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE. Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed. Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result (P < 0.0001). Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

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Prognostic factors and survival after whole-brain radiotherapy for initial brain metastases arising from non-small cell lung cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000030 ◽

2021 ◽

pp. 1-6

Author(s):

Yukinori Okada ◽

Mariko Kobayashi ◽

Mio Shinozaki ◽

Tatsuyuki Abe ◽

Naoki Nakamura

Keyword(s):

Prognostic Factors ◽

Brain Metastasis ◽

Brain Metastases ◽

Gene Mutation ◽

Stage Iv ◽

Whole Brain Radiotherapy ◽

Hazard Ratio ◽

Small Cell Lung ◽

Mutation Status ◽

Brain Radiotherapy

Abstract Aim: To identify prognostic factors and investigate patient survival after whole-brain radiotherapy (WBRT) for initial brain metastases arising from non-small cell lung cancer (NSCLC). Methods: Patients diagnosed with NSCLC between 1 January 2010 and 30 September 2019, and who received WBRT upon first developing a brain metastasis, were investigated. Overall survival was determined as related to age, sex, duration between initial examination and brain metastasis detection, stage at the first examination, presence of metastases outside the brain, blood analysis findings, brain metastasis symptoms, radiotherapy dose and completion, imaging findings, therapeutic course of chemotherapy and/or radiation therapy, histological type, and gene mutation status. Results: Thirty-one consecutive patients (20 men and 11 women) with a mean age of 63·8 years and median survival of 129 days were included. Multivariate analysis with stepwise testing was performed to investigate differences in survival according to gene mutation status, lactate dehydrogenase (LDH) level, irradiation dose, WBRT completion and Stage status. Of these, a statistically significant difference in survival was observed in patients with gene mutation status (hazard ratio: 0·31, 95% CI: 0·11–0·86, p = 0·025), LDH levels <230 vs. ≥230 IU/L (hazard ratio: 4·08, 95% CI: 1·45–11·5, p < 0·01) received 30 Gy, 30 Gy/10 fractions to 35 Gy/14 fractions, and 37·5 Gy/15 fractions (hazard ratio: 0·26, 95% CI: 0·09–0·71, p < 0·01), and stage IV versus non-stage IV (hazard ratio: 0·13, 95 CI:0·02–0·64, p < 0·01) Findings: Gene mutation, LDH, radiation dose and Stage are prognostic factors for patients with initial brain metastases who are treated with WBRT.

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CanAssist Breast Impacting Clinical Treatment Decisions in Early-Stage HR+ Breast Cancer Patients: Indian Scenario

Indian Journal of Surgical Oncology ◽

10.1007/s13193-019-01014-4 ◽

2019 ◽

Cited By ~ 2

Author(s):

Satish Sankaran ◽

Jyoti Bajpai Dikshit ◽

Chandra Prakash SV ◽

SE Mallikarjuna ◽

SP Somashekhar ◽

...

Keyword(s):

High Risk ◽

Early Stage ◽

Risk Groups ◽

Treatment Decisions ◽

Low Risk ◽

Not Given ◽

Breast Cancer Patients ◽

Number Of Patients ◽

Risk Of Cancer ◽

The Impact

AbstractCanAssist Breast (CAB) has thus far been validated on a retrospective cohort of 1123 patients who are mostly Indians. Distant metastasis–free survival (DMFS) of more than 95% was observed with significant separation (P < 0.0001) between low-risk and high-risk groups. In this study, we demonstrate the usefulness of CAB in guiding physicians to assess risk of cancer recurrence and to make informed treatment decisions for patients. Of more than 500 patients who have undergone CAB test, detailed analysis of 455 patients who were treated based on CAB-based risk predictions by more than 140 doctors across India is presented here. Majority of patients tested had node negative, T2, and grade 2 disease. Age and luminal subtypes did not affect the performance of CAB. On comparison with Adjuvant! Online (AOL), CAB categorized twice the number of patients into low risk indicating potential of overtreatment by AOL-based risk categorization. We assessed the impact of CAB testing on treatment decisions for 254 patients and observed that 92% low-risk patients were not given chemotherapy. Overall, we observed that 88% patients were either given or not given chemotherapy based on whether they were stratified as high risk or low risk for distant recurrence respectively. Based on these results, we conclude that CAB has been accepted by physicians to make treatment planning and provides a cost-effective alternative to other similar multigene prognostic tests currently available.

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Twenty-one-gene recurrence score (RS) in germline (g)CHEK2 mutation-associated versus sporadic breast cancers (BC): A multi-site case-control study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10531 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10531-10531

Author(s):

Anosheh Afghahi ◽

Sydney Marsh ◽

Alyse Winchester ◽

Dexiang Gao ◽

Hannah Parris ◽

...

Keyword(s):

Lymph Node ◽

Genetic Testing ◽

High Risk ◽

Case Control Study ◽

Case Control ◽

Low Risk ◽

Mutation Status ◽

T Stage ◽

Chek2 Mutation ◽

Control Study

10531 Background: Genomic assays, such as RS, are used to determine chemotherapy benefit in early-stage, estrogen receptor (ER)- and/or progesterone receptor (PR)-positive, HER2 negative BC patients (pts). Currently, guidelines to use pts’ germline genetic testing results to guide adjuvant therapy are lacking. Several reports have indicated worse outcomes for BC pts with g CHEK2 pathogenic variants (PV). We investigated whether PV in CHEK2 were associated with increased RS. Methods: Patient-level clinical data and RS were derived from electronic medical records of seven medical centers between years 2013-17. Confirmation of RS using the Genomic Health provider portal was performed. 38 pts with germline PV in CHEK2 (15 pts/39.5% with c.1100delC mutation) and RS score (cases) were matched with BC pts whose genetic testing did not identify PV (controls) using a 1:2 matching schema. Pts were matched based on age at diagnosis and lymph node (LN) status. LN negative pts were further matched based on T-stage. A multivariate random intercept linear mixed model of CHEK2 mutation status on RS was performed, adjusting for PR. A secondary ordinal univariate analysis was conducted that categorized RS into low, intermediate and high risk ( < 18, 18-30, and > 30, respectively). P-values were reported based on a null hypothesis of no effect against a two-sided alternative. Results: The median RS for cases was 19.5 (interquartile range [IQR]: 15 to 25) and the median RS for controls was 18 (IQR: 12 to 22). A greater proportion of cases were categorized as high risk (10.5%) compared to controls (5.6%), and a smaller proportion of cases were categorized as low risk (36.8%) compared to controls (49.3%). Cases had higher grade and increased proportion of PR-negative BC as compared with controls (grade 1: 12.1% of cases versus 32.4% of controls; PR-negative: 7.9% of cases versus 5.6% of controls). The variables used to match cases and controls (age, lymph node status, and T-stage) had similar summary statistics. The RS was 1.97-point higher in pts with g CHEK2 PV compared to controls, after adjusting for PR (95% confidence interval [CI]: 1.02-point lower to 4.96-point higher; p = 0.194). The secondary analysis of CHEK2 mutation status on an ordinal RS risk group yielded comparable results; on average, the odds of being high risk compared to the combined intermediate/low risk groups was 1.72 times higher in cases compared to controls (95% CI: 0.77 to 3.80; p = 0.181), but these differences were not significant. Conclusions: Our case-control study did not show a statistically higher RS for BC that develops in pts with g CHEK2 PV. Further studies are warranted to evaluate the association between type of CHEK2 PV (frameshift versus missense) and other modifying genetic variables and RS.

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The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5061 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5061-5061

Author(s):

Matthew R. Cooperberg ◽

Paul Brendel ◽

Daniel J. Lee ◽

Rahul Doraiswami ◽

Hariesh Rajasekar ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Language Processing ◽

Care Delivery ◽

Specific Antigen ◽

Risk Groups ◽

Low Risk ◽

T Stage ◽

Risk Stratum ◽

The Impact

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]

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