scholarly journals Genomic profiles and clinical outcomes of de novo blastoid/pleomorphic MCL are distinct from those of transformed MCL

2020 ◽  
Vol 4 (6) ◽  
pp. 1038-1050 ◽  
Author(s):  
Preetesh Jain ◽  
Shaojun Zhang ◽  
Rashmi Kanagal-Shamanna ◽  
Chi Young Ok ◽  
Krystle Nomie ◽  
...  
Keyword(s):  
De Novo ◽  
Performance Status ◽  
Regression Tree ◽  
Poor Performance ◽  
Patient Characteristics ◽  
Integrated Analysis ◽  
Poor Performance Status ◽  
Ki 67 ◽  
Regression Tree Analysis ◽  
Poor Outcomes

Abstract Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P = .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (<50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.

scholarly journals Case Report: Ectopic Adrenocortical Carcinoma in the Ovary

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen-Hsuan Tsai ◽  
Tze-Chien Chen ◽  
Shuen-Han Dai ◽  
Yi-Hong Zeng
Keyword(s):  
Adrenocortical Carcinoma ◽  
Performance Status ◽  
Poor Performance ◽  
Abdominal Circumference ◽  
Poor Performance Status ◽  
Test Results ◽  
Ki 67 ◽  
Complete Survey ◽  
Rare Malignancy ◽  
Captopril Test

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/million habitants/year. ACCs are rare and usually endocrinologically functional. We present the case of a 59-year-old woman who experienced abdominal fullness for 6 months and increased abdominal circumference. A large pelvic tumor was observed. She underwent cytoreductive surgery and the pathological test results revealed local tumor necrosis and prominent lympho-vascular invasion. Neuroendocrine carcinoma was the first impression, but positivity for synaptophysin, alpha-inhibin, transcription factor enhancer 3 (TFE-3), calretinin (focal), and CD56 (focal) and high Ki-67-labeling proliferating index (>80%) confirmed the diagnosis of ectopic ACC. Ectopic primary aldosteronism could not be excluded. However, we did not perform saline infusion test or captopril test due to poor performance status. When pathological test reports reveal neuroendocrine features not typically found in the organ being examined, IHC staining should be performed to rule out ectopic ACC. Whether the ectopic ACC is functional or not requires complete survey.

Current trend in incidence of severe interstitial lung disease (ILD) due to gefitinib in Japan

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19075-e19075
Author(s):  
K. Goto ◽  
H. Kenmotsu ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
H. Ohmatsu ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Performance Status ◽  
Current Trend ◽  
Poor Performance ◽  
Female Gender ◽  
Patient Characteristics ◽  
Japanese Patients ◽  
Cancer Center ◽  
Poor Performance Status ◽  
Almost All

e19075 Background: Although gefitinib is a promising agent for the treatment of advanced non-small cell lung cancer, ILD occurs in Japanese patients and sever ILD sometimes becomes fatal toxicity. ILD has been reported to be associated with preexisting ILD, smoking, and poor performance status. On the other hand, it has been reported that female gender, adenocarcinoma, non-smoker, and EGFR mutation are associated with sensitivity to gefitinib. Methods: To investigate the trend in incidence of severe ILD and patient characteristics receiving gefitinib, a total of 751 patients who were administered gefitinib in National Cancer Center Hospital East between 2002 and 2008 were retrospectively reviewed. To investigate how oncologists avoid administering gefitinib to patients with preexisting ILD, pretreatment chest CT films of all patients were also reviewed by two thoracic radiologists. Results: The patient number who received gefitinib in 2002/2003/2004/2005/2006/2007/2008 were 134/141/88/93/125/98/72, respectively. In these patients, percentages of female were 36/43/42/55/59/52/54%, adenocarcinoma 76/78/93/88/95/93/92%, non-smoker 35/30/40/53/49/48/46%, respectively. Almost all of the patient receiving gefitinib was recently restricted to adenocarcinoma. Grade 3–5 severe ILD was observed in 1.9% of all patients. However, the incidence rate of sever ILD were decreased as 3.0/2.8/2.3/1.1/0.8/1.0/1.4%, respectively. The rates of patients with preexisting ILD were also decreased as 22/14/15/5/2/3/6%, respectively. Conclusions: The correct information about efficacy and severe ILD about gefitinib influenced patient selection by oncologists, and it is reasonable to select more effective and safe patients in Japan. It is estimated that the incidence rate of severe ILD should be consequently controlled by the spread of these information. No significant financial relationships to disclose.

Predicting survival in resected pancreatic cancer: A Canadian provincial experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 361-361
Author(s):  
Gillian Gresham ◽  
Sylvia Ng ◽  
Anderson Chang ◽  
Shannon Valdez ◽  
Sharlene Gill
Keyword(s):  
Pancreatic Cancer ◽  
Histological Grade ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Significant Difference ◽  
Cancer Agency ◽  
Trial Outcomes ◽  
Grade 3 ◽  
Poor Outcomes

361 Background: Surgical resection offers the only hope for long-term disease control in patients (pts) with pancreatic adenocarcinoma. Randomized trials (ESPAC 1, ESPAC3) further support a role for adjuvant chemotherapy (AC) in the management of pancreatic cancer (PC). Trial outcomes may not reflect clinical reality due to pt selection bias, and it is often difficult to predict which pts are most likely to benefit from adjuvant intervention. Methods: Consecutive pts between 2003 and 2008 referred to the BC Cancer Agency (BCCA) with operative intent at diagnosis (dx) were retrospectively reviewed. Results: 145 pts were identified; median age 65 years (y) (range 38-84), male/female (45.5%, 54.5%). EUS/PET staging was performed in 21% of pts. Median CA19-9 value at dx was 210 ku/L. Pancreaticoduodenectomy was performed in 65% of pts. Complete resection (RO) of tumours occurred in 87 pts (60%) overall. 66% of pts were node positive. 43% of pts were subsequently treated with adjuvant therapy (AT) where 5% of these pts received chemoradiotherapy and 95% received AC (65% gemcitabine). There was no statistically significant difference in either OS (p=0.39) or DFS (p=0.28) amongst resected pts who were treated by sx alone versus pts who received AC. In subgroup analysis, AC was associated with significantly improved OS in pts (n=58) with positive margins (R1) (median 17.3 mos vs 8.9 mos, p=0.0045) but benefit was not seen in R0 pts (n=87) (22.9 mos vs 22.4 mos, p=0.20). In multivariate analysis, poor performance status (ECOG 3-4), weight loss of more than 10% of initial body weight, baseline CA19-9 value greater than 210 ku/L, positive nodes, R1 status and histological grade 3-4 were significant adverse prognostic factors. Conclusions: PC continues to have poor outcomes with a 5yOS of 5% in pts treated with sx alone. Among pts with resectable PC treated at the BCCA, AC tended towards increased DFS and OS. Although R1 status was associated with inferior OS, the benefit of AT was greater in this subgroup. [Table: see text]

Atezolizumab (atezo) therapy for locally advanced/metastatic urinary tract carcinoma (mUTC) in patients (pts) with poor performance status (PS): Analysis of the prospective global SAUL study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5035-5035
Author(s):  
Daniel Castellano ◽  
Craig Gedye ◽  
Giuseppe Fornarini ◽  
Andre P. Fay ◽  
Jens Voortman ◽  
...  
Keyword(s):  
Performance Status ◽  
Locally Advanced ◽  
Poor Performance ◽  
Poor Performance Status ◽  
World Population ◽  
Dismal Prognosis ◽  
Visceral Metastases ◽  
Baseline Factors ◽  
Poor Outcomes ◽  
Ecog Ps

5035 Background: Pts with PS > 1 have a poor prognosis and are often excluded from clinical trials. The single-arm SAUL study (NCT02928406) evaluated atezo in a ‘real-world’ population. Overall, safety and efficacy were consistent with prior trials. However, ECOG PS 2 pts had worse overall survival (OS) but fewer adverse events (AEs) than ECOG PS 0/1 pts [Sternberg, 2019], likely reflecting shorter treatment duration and warranting exploration. Methods: Pts with mUTC received atezo 1200 mg q3w until loss of clinical benefit or unacceptable toxicity. The primary endpoint was safety. Post hoc analyses compared baseline factors, AEs and efficacy in pts with ECOG PS 2 vs 0/1. In this analysis, AE incidences were restricted to the first 45 days of atezo to adjust for differing treatment exposure. Results: None of the baseline factors explored was significantly associated with worse OS or disease control rate (DCR) in ECOG PS 2 pts. However, pts with visceral metastases and ECOG PS 2 had particularly poor outcomes. Safety appeared similar between subgroups. Conclusions: ECOG PS 2 pts have a dismal prognosis. The higher proportion with poor prognostic factors despite similar age in ECOG PS 2 vs 0/1 pts may suggest that poor PS was related to disease rather than comorbidities. Risk/benefit should be considered especially carefully when treating pts with ECOG PS 2 due to high-burden/visceral disease. Clinical trial information: NCT02928406 . [Table: see text]

scholarly journals No Prognostic Impact of p53 and P-Glycoprotein Expression in Patients with Diffuse Large B-Cell Lymphoma

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Pairaya Rujirojindakul ◽  
Kumpol Aiempanakit ◽  
Kanita Kayasut ◽  
Arnuparp Lekhakula ◽  
Hutcha Sriplung
Keyword(s):  
De Novo ◽  
Performance Status ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
Prognostic Impact ◽  
P Glycoprotein ◽  
Formalin Fixed Paraffin Embedded

The aim of this study was to determine the clinical significances of p53 and p-glycoprotein (P-gp) expression on outcome predictors for patients with DLBC. We assessed the immunohistochemical expression of p53 and P-gp using formalin-fixed, paraffin-embedded specimens in 108 patients diagnosed with de novo DLBC. A high expression of p53 was found in 53.7% of the patients. No expression of P-gp was demonstrated in any of the specimens. There were no significant differences in the complete remission (CR) rate (P=0.79), overall survival (OS) (P=0.73), or disease-free survival (DFS) (P=31) between the p53-positive and p53-negative groups. The final model from multivariate analysis that revealed poor performance status was significantly associated with CR (P<0.001) and OS (P<0.001). Moreover, the advanced stage was a significant predictor of DFS (P=0.03). This study demonstrated no impact of the expression of p53 on either response or survival rates.

scholarly journals A real-world registry to evaluate HER2-directed therapy in Australian patients with metastatic breast cancer (MBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12515-e12515
Author(s):  
Margaret Lee ◽  
Sheau Wen Lok ◽  
Natalie Heather Turner ◽  
Daphne Day ◽  
Sally Greenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
De Novo ◽  
Performance Status ◽  
Metastatic Breast ◽  
Poor Performance ◽  
Poor Performance Status ◽  
First Line ◽  
Her2 Positive ◽  
Substantial Impact

e12515 Background: The management and outcomes of HER2 positive MBC have dramatically evolved with the introduction of HER2-targeted therapies. However, limited data regarding the uptake, impact and safety of these treatments in the real-world context, prompted us to initiate a comprehensive registry across multiple settings in Australia. Methods: We examined the multisite electronic registry TABITHA (Treatment of Advanced Breast Cancer in the HER2 positive Australian Patient) to capture clinical data of consecutive patients diagnosed with HER2 positive MBC between Jan 2016-Jan 2017. Patient demographics, use and outcomes of treatment were explored. Results: An initial cohort of 74 patients was identified, 28 (38%) with de novo metastatic and 46 (62%) with relapsed disease. The median age at presentation with MBC was 57 years (range 27-83), with main metastatic sites being bone (n = 41, 55%), major organs (n = 40, 54%), locoregional (N = 26, 35%) and central nervous system (n = 13, 18%). In total, 64 (86%) patients had received first-line HER2 therapy, including trastuzumab plus pertuzumab (n = 48, 75%), trastuzumab alone (n = 10, 16%) and trastuzumab-emtansine (n = 6, 9%). Ten patients had not received any HER2 therapy, of which 8 received best supportive care alone, 1 received endocrine therapy, and 1 received anti-resorptive therapy. The median age of non-HER2 treated patients was 61 (range 44-81) and 40% were ECOG 2+ compared to 25% of patients receiving HER2 therapy (p = NS). First-line HER2 therapy had been discontinued in 20/63 (32%) patients, due to progressive disease (n = 18, 90%) or toxicity (n = 2, 10%). Median time to progression was 12.7+ months (range 2.0-81.9+). Conclusions: Whilst trials of HER2 directed therapies have demonstrated a substantial impact on survival outcomes for MBC with modest toxicity, a proportion of HER2 positive patients in routine care may not receive these agents. Poor performance status contributes to non-HER2 therapy use, however data collection is ongoing and other potential drivers will be further examined. Where HER2 directed therapies are used, the preliminary data indicates good activity with the majority of patients still currently on treatment.

scholarly journals A Review of Recent Advances in the Treatment of Elderly and Poor Performance NSCLC

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 236 ◽  
Author(s):  
Juliet Carmichael ◽  
Daisy Wing-san Mak ◽  
Mary O’Brien
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Recent Advances ◽  
Targeted Treatments ◽  
Potential Activity ◽  
Poor Outcomes

Until recently, chemotherapy has remained the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC). Excellent responses have been observed with immune-checkpoint inhibitors, and targeted treatments for those tumours with actionable mutations, resulting in a paradigm shift in the treatment approach for these patients. Elderly patients and those with poor performance status (PS), such as Eastern Cooperative Oncology Group (ECOG) 2, have historically been excluded from clinical trials due to poor outcomes. There is therefore a lack of data to define the optimal treatment strategy for these patients. Due to improved tolerability of novel therapies, inclusion of these patients in clinical trials has increased, and sub-group analyses have identified many treatments demonstrating potential activity. Here, we summarise key recent advances in the treatment of NSCLC, specifically evaluating their efficacy and tolerability in these patient cohorts.

Erlotinib and bevacizumab in chemotherapy-naive performance status 2 patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19082-e19082
Author(s):  
T. Al Baghdadi ◽  
N. Hanna ◽  
S. Bhatia ◽  
J. McClean ◽  
C. Johnson ◽  
...  
Keyword(s):  
Alternative Hypothesis ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Patient Characteristics ◽  
Poor Performance Status ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Patient Reported

e19082 Background: Poor performance status is a negative prognostic variable for survival and a risk for increased toxicities with standard chemotherapy. A phase 2 study combining erlotinib (E) and bevacizumab (B) demonstrated encouraging efficacy in the treatment of recurrent NSCLC with acceptable toxicity. We, therefore, tested this regimen in untreated PS 2 patients with advanced NSCLC. Methods: Single-arm phase 2 trial in treatment-naïve patients with advanced non-squamous NSCLC and either a PS of 2 or age >75. Only patients eligible for bevacizumab per label were allowed onto study. Patients received E 150 mg orally daily and B 15 mg/kg IV on day 1 every 21 days for up to 6 cycles. The primary end-point was the rate of non progressive disease at 4 months (alternative hypothesis P>60%). Other end-points included overall survival, progression free survival (PFS), toxicity evaluations and patient-reported PS (PRPS) measures. Results: 25 patients were enrolled. Patient characteristics: 56% female, median age 77 years (range: 52–90); 88% stage IV; 92% were PS 2; 20% were never or remote smokers (> 30 years) The PRPS was 1, 2, 3 in 32%, 52%, 8% respectively with data on 2 patients missing. The rate of non-progression at 4 months was 40%; overall best response: 5% PR, 40% SD, 50% PD and 5% unevaluable; median PFS 2.6 months, 95% CI (1.3–5.1); MST 5.8 months, 95% CI (3.8- 8.7). 2 patients had G3 rash. G3 diarrhea, G3 hemorrhage, G3 proteinuria, G3 duodenal ulcer and G3 pneumonitis each developed in one patient. Conclusions: E + B is an active regimen with an acceptable toxicity profile; however, this study did not meet its’ primary endpoint. Further study of this combination will not be pursued in the Hoosier Oncology Group for this patient population. [Table: see text]

Toxicity following palliative radiation therapy for painful metastatic bone lesions.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
Mikayla Jenkins ◽  
Mark Raymond Waddle ◽  
Tasneem Kaleem ◽  
William C Stross ◽  
Timothy D Malouff ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Radiation Treatment ◽  
Performance Status ◽  
Poor Performance ◽  
Patient Characteristics ◽  
Bone Lesions ◽  
Poor Performance Status ◽  
Financial Toxicity ◽  
Palliative Radiation ◽  
Ed Visits

126 Background: Palliative radiation treatment (pRT) is a common and effective treatment for patients with symptomatic bone metastases. However, patients receiving RT for bone metastases often may have a poor performance status and are more likely to experience toxicity during or after treatment. This study aims to investigate the number and type of toxicity event occurring during or after pRT for bone metastases. Methods: Patients treated with RT for bone metastases at Mayo Clinic from 2007 to 2016 were included in this study. Demographic, disease, treatment, and toxicity information were collected. Specifically, toxicity events were identified as emergency department (ED) visits and inpatient hospitalization (IH) within 90 days, breaks in treatment >4 days, and excessive 30 day financial toxicity defined as standardized Medicare costs >1 standard deviation above the mean. RT treatment was compared by dose and fractionation via descriptive statistics. Results: A total of 538 patients treated with pRT were identified, 124 receiving 8Gy x1, 204 receiving 4Gy x5, and 210 receiving 3Gy x10. Patients with breast and prostate cancer were most likely to be treated with 3Gy x10 and patients with GI and Lung cancer were most likely to be treated with 8Gy x1. A description of the patient characteristics and toxicities are shown in Table 1. For 8Gy x1, 4Gy x5, and 3Gy x10 breaks in treatment were rare (0%, 2%, and 3.3%), ED visits (15%, 24%, & 28%), IH (12%, 23%, & 19%), and financial toxicity (13%, 18%, & 21%) were common. A total of 22.6%, 27.5%, and 38.6% of patients were alive two years following pRT from each group. Conclusions: Toxicity during or shortly after pRT of bone metastases is common. This study confirms that additional steps should be taken to monitor and mitigate toxicity in this vulnerable patient group. [Table: see text]

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