scholarly journals Stereotactic body radio therapy for inoperable large hepatocellular cancers: results from a clinical audit

2019 ◽  
Vol 92 (1101) ◽  
pp. 20181053 ◽  
Author(s):  
Supriya Chopra ◽  
Karishma George ◽  
Reena Engineer ◽  
Karthick Rajamanickam ◽  
Siji Nojin ◽  
...  
Keyword(s):  
Local Control ◽  
Clinical Audit ◽  
Progression Free Survival ◽  
Normal Liver ◽  
Tumour Volume ◽  
P Value ◽  
Free Survival ◽  
Hepatocellular Carcinomas ◽  
Radio Therapy ◽  
Good Local Control

Objectives: To evaluate the outcomes of stereotactic radiotherapy (SBRT) in the treatment of inoperable hepatocellular carcinomas (HCC) that are unsuitable for, or refractory to other liver-directed therapies. Methods: Between March 2015 and June 2018, patients with primary HCCs refractory to or unsuitable for treatment with other liver-directed therapies were treated with SBRT. Patients of Child status A5-B7 and with normal liver reserve ≥ 700 cc were preferred. Local control (LC), overall survival (OS), progression free survival (PFS) and effect of prognostic factors were analysed. Results: 21 patients with inoperable HCCs were treated. The median tumour diameter was 9.6 cm (5-21) and median tumour volume was 350 cc (32.9 – 2541). The median SBRT dose prescription was 42 Gy/6 fractions (25 – 54 Gy/6#). The 1- and 2-year LC rate was 88 and 43 % respectively. Overall rate of > grade III toxicity was 14 %. Patients with Child A5 liver function had a better median OS than A6 and B7 patients [21 vs 11 vs 8 months]. Also, tumours with GTV < 350 cc volumes had a better OS compared to GTV of greater than 350 cc [24 months vs 8 months, p value = 0.004]. Conclusions: This study showed that SBRT can be used safely and effectively to treat inoperable HCCs with or without prior loco-regional therapies, resulting in good local control and survival with acceptable toxicity. Advances in knowledge: Use of SBRT in inoperable HCC is safe and effective.

Comparative Survival Assessment of Two-Dimension (2D) versus Three-Dimension (3D) Brachytherapy Treatment in Locally Advanced Cervical Cancer: A Retrospective Case Control Study

2021 ◽  
Vol 104 (6) ◽  
pp. 934-942
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Progression Free Survival ◽  
P Value ◽  
Three Dimension ◽  
Retrospective Case ◽  
Ct Guided ◽  
Free Survival ◽  
Grade 3

Objective: To assess the efficacy as seen as overall survival, local control, progression free survival (PFS) and toxicities, between two-dimension (2D) and three-dimension (3D) computed tomography (CT) guided brachytherapy (BT) without using interstitial needles among patients with cervical cancer. Materials and Methods: A retrospective case control study was performed among patients with FIGO stage IB-IVA cervical cancer treated between March 1990 and August 2018. Concurrent chemoradiation using external beam radiotherapy followed by BT was the treatment method used in all patients. Patients were divided in two groups based on imaging type during BT to compare between 2D and 3D BT techniques. Clinical endpoints were overall survival, local control, progression free survival, acute toxicities, and late toxicities. Results: One hundred two patients with cervical cancer were included, which 52 patients had been treated with 2D and 50 patients with 3D using CT scan BT without interstitial needles. Baseline characteristics were similar between the groups. External beam was used among all patients during the concurrent chemoradiation period before BT. All patients completed the treatment. Similar 3-year overall survival and local control were reported between 2D and 3D techniques. Overall, the 3-year survival rate was 95.7% in 2D and 91.8% in 3D BT (p=0.188). Local control at the 3-year follow-up was 88.6% for 2D and 93.3% for 3D treatment (p-value=0.571). Progression free survival was better in the 2-D rather than the 3D group with 86.13% in 2D versus 27.4% in the 3D group (p-value=0.006). No grade 3 or 4 toxicity regarding the 3D technique was observed whereas 1.9% of grade 3 presented acute gastrointestinal toxicity (p-value=1), and grade 3 late gastrointestinal and genitourinary toxicities in the 2D technique group at 7.7 and 5.8%, respectively (p=1, both). The 3D BT significantly reduced acute grade 1 to 2 gastrointestinal side effect as 23% in the 2D versus 4% in 3D group (p-value=0.003), and grade 1 to 2 late genitourinary side effect as 50% in the 2D versus 16% in the 3D group (p-value=0.001). Conclusion: Using CT guided 3D BT to treat cervical cancer showed similar outcomes in survival and local control but reduced toxicity compared with the 2D technique. Disease progression including metastasis was better in the 2D BT technique group. CT guided BT helped reduce dose to organs at risk and long-term follow-up for survival outcome and toxicities was needed. Keywords: Cervical cancer; Brachytherapy technique; Brachytherapy; 3D brachytherapy; 2D brachytherapy

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

scholarly journals NOVEL PLASMA GLYCOPROTEIN BIOMARKERS PREDICT PROGRESSION-FREE SURVIVAL IN SURGICALLY RESECTED CLEAR CELL RENAL CELL CARCINOMA

2022 ◽  
Author(s):  
Daniel Serie ◽  
Amanda A Myers ◽  
Daniela A Haehn ◽  
Alexander Parker ◽  
Essa Bajalia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differential Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Progression Free Survival ◽  
P Value ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Kaplan Meier

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

scholarly journals Early intra-treatment diffusion weighted magnetic resonance imaging in patients with recurrent nasopharyngeal carcinoma treated with nivolumab

2020 ◽  
Vol 6 (3) ◽  
pp. 568
Author(s):  
Tiffany Y. So ◽  
Qi-Yong Ai ◽  
Brigette B.Y. Ma ◽  
Ann D. King
Keyword(s):  
Magnetic Resonance Imaging ◽  
Overall Survival ◽  
Magnetic Resonance ◽  
Nasopharyngeal Carcinoma ◽  
Progression Free Survival ◽  
Tumour Volume ◽  
Resonance Imaging ◽  
Free Survival ◽  
Diffusion Weighted ◽  
Weighted Magnetic Resonance Imaging

<p class="abstract">Immune check point inhibitors have demonstrated promising efficacy in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) in phase I and phase II trials. Early identification of treatment response is important in these patients. This report aimed to document the early intratreatment diffusion weighted magnetic resonance imaging (DW-MRI) findings in NPC patients following treatment with the programmed cell death-1 inhibitor, nivolumab. Two consecutive patients with histologically confirmed recurrent undifferentiated NPC treated with nivolumab were prospectively recruited. Nivolumab was administered at a dosage of 3 mg/kg intravenously every 2 weeks. Patients underwent magnetic resonance imaging examinations at baseline, and at 3 and 5 weeks after commencement of treatment. Intratreatment changes in tumour volume and apparent diffusion coefficient (ADC<sub>mean</sub>)were calculated. The endpoints were objective response by response evaluation criteria in solid tumors and survival. In patient 1, an intratreatment ADC increase at 5 weeks corresponded with anatomical tumour volume reduction and a better long-term survival outcome (progression free survival 1.3 years, overall survival 2.9 years). In patient 2, an intratreatment ADC decrease at 5 weeks corresponded to progressive disease and worse outcome (progression free survival 0.0 years, overall survival 0.9 years). Intratreatment ADC changes at 3 weeks were not associated with response outcome. These cases suggest that intratreatment changes in ADC at 5 weeks may potentially predict tumour response in patients treated with nivolumab. Dedicated studies are needed to clarify these findings and fully characterise patterns of treatment related ADC change.</p>

Patterns of Care and Treatment Pathways for Non-Surgically Managed Early and Locally Advanced Non-Small Cell Lung Cancer Patients at Ain Shams University Clinical Oncology Department: a Retrospective and Descriptive Analysis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Dr/Khaled Abdel Karim ◽  
Dr/Khaled Nagib ◽  
Dr/Ahmed Hassan Abd El Aziz ◽  
Christina Gamil Garas
Keyword(s):  
Overall Survival ◽  
Clinical Oncology ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Patterns Of Care ◽  
P Value ◽  
Treatment Pathways ◽  
Free Survival ◽  
Care And Treatment ◽  
Nsclc Patients

Abstract Background Lung cancer is the leading cause of cancer death worldwide, but little is known about how patients with this disease are managed. Aim of the Work We aim to study patterns of care and treatment pathways of non- surgically managed early and locally advanced NSCLC patients from January 2015 to December 2018 in Ain Shams University Clinical Oncology Department. Patients and Methods In this retrospective analysis we included patients the met the following criteria; age &gt;18, histologically confirmed NSCLC patients whom didn’t undergo surgical resection with at least 6 months of follow up data. We collected data from Clinical Oncology department archive in Ain Shams university hospital. Our primary objective is to identify the patterns of care and treatment pathway for non surgically managed NSCLC patients in ASUCOD from January 2015 to December 2018. Results 86 patients finally met our inclusion criteria. Median age at diagnosis of 61 years with a range of (38-85), 95.3% were male. Most of the patients were stage III; 40.7% were stage IIIA, 41.9% were stage IIIB, and 9.3% were stage IIIC. 41 were treated radically, 37 received palliative treatment and only 8 patients received supportive care. Overall median progression free survival in our patients was 9.23 (7.4-13.5) and overall survival duration was13.4 (9.5-18.0). In radically treated patients, 68.3% received sequential chemoradiotherapy (sCRT), 29.2% received concurrent chemoradiotherapy (cCRT) or 2.4% received definitive radiotherapy alone (RT). In palliative treated patients, 73% received chemotherapy alone (CTX), 8.1% received palliative RT and 18.9% received both chemotherapy and palliative dose of radiotherapy (CRT). All treatment modalities were similar regarding median progression free survival and overall survival durations, 17.5 (3.6–19.6) and 20.6 (3.6–31.6) in cCRT, 17.5 (3.6–19.6) and 23.3 (17.7–31.2) in sCRT, 12.9 and 13.4 RT group, P value=0.57 and 0.16 receptively. Similarly, progression free survival and overall survival durations were 8.8 (3.0–15.8) and 16.2 (3.6–18.7) in CRT, 5.3 (0.4–7.6) and 8.6 (6.2–10.2) in CTX, 8.5 (0.4–8.5) and 8.5 (0.4–8.5) in palliative RT group, P value=0.64 and 0.15 receptively. In our study, first-line chemotherapy were Gemcitabine plus Cisplatin (41.9%) or Carboplatin (35.1%).The Second -line chemotherapy were Docetaxel (63.1%) or Paclitaxel plus Carboplatin (26.3%). Paclitaxel plus Carboplatin were the most regimen given with RT. Most of the patients received radiation dose of 60Gy/30Fr (73.2%). Regarding the incidence of toxicity, there were significant high rates of esophagitis in cCRT in grade 3 or more compared to sCRT. Conclusion We have found that less than half of this study population were treated radically while the other half received palliative treatment. And only few patients received best supportive care. Radically treated patients had higher progression free survival and overall survival durations compared to palliative and supportive treatment.

Stereotactic radiotherapy in patients with oligometastatic or oligoprogressive gynecological malignancies: a multi-institutional analysis

2020 ◽  
Vol 30 (6) ◽  
pp. 865-872 ◽  
Author(s):  
Cem Onal ◽  
Melis Gultekin ◽  
Ezgi Oymak ◽  
Ozan Cem Guler ◽  
Melek Tugce Yilmaz ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Stereotactic Body Radiotherapy ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
Term Survival ◽  
Free Survival ◽  
Oligometastatic Disease

IntroductionData supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer.MethodsThe clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival.ResultsA total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9–95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0–16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities.ConclusionsPatients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival.

Concurrent 5-Fluorouracil, Mitomycin C and Radiation, with or without Brachytherapy, in Recurrent Endometrial Cancer: A Scoring System to Predict Clinical Response and Outcome

2005 ◽  
Vol 91 (3) ◽  
pp. 215-220 ◽  
Author(s):  
Daniela Smaniotto ◽  
Giuseppe D'Agostino ◽  
Stefano Luzi ◽  
Vincenzo Valentini ◽  
Gabriella Macchia ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mitomycin C ◽  
Local Control ◽  
Progression Free Survival ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
Free Survival ◽  
Recurrent Endometrial Cancer ◽  
Grade 3

Aims and background This prospective, phase II study aimed to test the efficacy of concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, on the clinical outcome of a series of recurrent endometrial cancer patients and to determine the prognostic impact of a subset of factors. Methods Thirty patients with locally recurrent, nonmetastatic endometrial cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continous infusion, days 1-4; 1 g/m2/day; mitomycin C, 10 mg/m2, bolus iv, day 1). Nineteen patients (63.3%) underwent endocavitary, low-dose brachytherapy boost (20-25 Gy); eight patients (26.7%) received external beam radiation boost (14-20 Gy). Results Eleven complete responses (36.7%), 11 partial responses (36.7%), 6 disease stabilizations (20.0%) and 2 progressions (6.6%) were observed. After a median follow-up of 27 months (range, 1-108), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 46.8%, 35.2% and 41.2%, respectively. Two patients (6.7%) experienced hematological grade 3 toxicity. Two patients (6.7%) had grade 3 intestinal toxicity. Severe late toxicity was infrequent, only 3 patients showing severe vaginal stenosis (10.0%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin <11 g/dL. With this device, it was clear that patients with a low score had a significantly better outcome (clinical remission: 77.2% of patients with a score <2 vs 25.0% of patients with a score ≥2, P = 0.009), better local control of the disease (50.2% vs. 0 at 3 years, P = 0.014,) and better overall survival (65.8% vs 0 at 3 years, P = 0.003). Conclusions Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful in identifying patients with the best chance of benefiting from the treatment.

High-Dose Imatinib Mesylate Treatment in Patients (Pts) with Previously Untreated Early Chronic Phase (CP) Chronic Myeloid Leukemia (CML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 999-999 ◽  
Author(s):  
Jorge Cortes ◽  
Moshe Talpaz ◽  
Susan O’Brien ◽  
Francis Giles ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Standard Dose ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
P Value ◽  
High Dose ◽  
Free Survival ◽  
Clinical Observations ◽  
Pre Treatment ◽  
Grade 3

Abstract Imatinib has become the treatment of choice for most with CML. The standard dose (SD) for CP CML is 400 mg daily, but pre-clinical and clinical observations suggest that higher doses (HD) may be more effective. We have treated 222 with previously untreated CML in early CP with imatinib in 3 consecutive trials: one using SD imatinib (400 mg/day) (n=50; all entered in April 2001) and 2 subsequent trials using 400 mg twice daily (total dose 800 mg/day) (n= 172; from June 2001 until present). The 2 HD trials had identical inclusion criteria and will be considered together for this analysis. Pts followed for at least 3 months (mo) are evaluable (n=210) for this report (n=49 at 400mg, 161 at 800 mg). The median age was 48 years (range, 15 to 84); platelets were >450 x109/L in 71 pts (34%), 78 (37%) had peripheral blood (PB) blasts, and 11 (5%) had clonal evolution. Sokal risk group classification was good in 128 (61%) pts, intermediate in 61 (29%) pts, and poor in 21 (10%) pts. There was no difference in pre-treatment characteristics between the standard SD and HD groups. The results at 18 months are as follows: Response % Response p value* 400 mg/day 800 mg/day CR=Complete remission, Molecular Major=BCR-ABL/ABL <0.05%, Molecular CR=BCR-ABL undetectable (confirmed by nested PCR), *p value by log-rank Median follow-up (months) 36 19 Cytogenetic CR 81 96 0.0002 Cytogenetic Major 99 93 0.15 Molecular Major 47 67 0.0007 Molecular CR 8 24 0.02 Four pts treated with SD have transformed (3 to BP, 1 to AP) and 3 (2 to BP, 1 to AP) in the HD groups (p=0.05) (median time to transformation 11 mo, range 3 to 27). Estimated progression-free survival at 12 mo is 92% in the SD group and 99% in the HD group (p=0.42) (p=0.12 for the estimated transformation-free-survival, 94% and 99% for SD and HD at 12 mo). 4 have died (1 in SD and 3 in HD). Extramedullary toxicity was similar in the 2 groups, but myelosuppression was more common with HD, with grade ≥3 anemia, neutropenia and thrombocytopenia occurring in 7%, 39%, and 27% of pts receiving HD, respectively, and 4%, 20% and 12% of pts receiving SD. At 12 mo, the median actual dose for the HD group is still 800mg, with 40/112 (36%) evaluable having required dose reduction. This compares with 7/43 (14%) of those treated with SD. We conclude that high-dose imatinib results in higher rates of complete cytogenetic and molecular remissions, with some increase in myelosuppression.

Effector T-cell cytolytic activity modules derived from CD3+ single cells from human primary triple-negative breast cancer (TNBC) in multiple solid tumors to predict response to immune checkpoint blockade therapy (ICB).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1073-1073
Author(s):  
Chaitanya Ramanuj Acharya ◽  
Herbert K Lyerly
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Single Cell ◽  
Single Cells ◽  
Progression Free Survival ◽  
Cytolytic Activity ◽  
Enrichment Score ◽  
P Value ◽  
Free Survival ◽  
Tumor Types

1073 Background: The prognostic and predictive value of tumor infiltrating lymphocytes for ICB has been recognized in a variety of tumor types, including TNBC. Nonetheless, our understanding of the mechanistic aspects of T cell activation remains incomplete. We hypothesize that a specific effector phenotype of T cell cytolytic activity (ECA) is a consistent feature of epithelial tumors, possibly varying by tumor types with a range of inflammatory features. Methods: We evaluated 6,311 purified CD3+ single cells from human primary TNBC and computed sample set enrichment scores of a set of previously published immune metagenes. Following unsupervised clustering of the enrichment scores of the entire single cell population, two subgroups of cells with highest and lowest average enrichment score of T cell cytolytic activity formed a basis for detecting functional gene expression modules. Spectral decomposition and Jackstraw analysis estimated eight modules with overlapping sets of genes. Each gene expression module was then used to train a Random Forest classifier of ECA phenotype. Results: We discovered that our module-derived classifiers were prognostic not only in TNBC samples obtained from both TCGA (N = 150) and METABRIC (N = 320) datasets but also in 14 other tumor types encompassing 6,000 samples. For example, patient samples from TCGA dataset predicted to be in group ECA ‘High’ have better progression-free survival (p-value: 0.0098l; HR: 0.30) and better overall survival (p-value: 0.0066; HR: 0.17). In both breast datasets, gene within the classifier are relatively under-expressed in ER+ tumors as opposed to HER2+ and TNBC (p-value < 2.2e-16). In a dataset of normal, pure DCIS and mixed DCIS (GSE26304;N = 114), the same genes were relatively under-expressed in DCIS samples relative to invasive tumors (p-value < 2.2e-16). Additionally, in a pre-therapy tumor dataset of fifty-one advanced melanoma patients treated with Nivolumab, who previously either progressed on ipilimumab or were ipilimumab-naïve, our module-derived classifier was able to classify responders and non-responders with 77% accuracy (p-value = 0.02) and was associated with progression-free survival (p-value = 0.03; HR: 0.28). Conclusions: Our study highlights one important application of single-cell genomics in our understanding of immune microenvironment and potentially identify new immunotherapy targets.

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