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  • American Society of Clinical Oncology (ASCO)  (5)
  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e17508-e17508
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e17508-e17508
    Abstract: e17508 Background: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. We aimed to analyze pretreatment 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and clinicopathological characteristics in patients with locally advanced cervical squamous cell carcinoma (SCC) to establish a scoring system for prognostic stratification. Methods: Cohort 1 consisted of patients with cervical SCC with FIGO (2009) stage III-IVA or stage I-II with positive nodes on PET/CT recruited in AGOG09-001 trial. Cohort 2 consisted of institutional patients treated in 2016-2020 with similar inclusion criteria. Pretreatment clinical characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of cervical tumor and nodal SUVmax were assessed for outcomes using the stepwise multivariable Cox regression. Results: With two cohorts combined (Cohort 1, n= 55, Cohort 2, n= 120), the median follow-up for 175 patients was 55 months (range, 2-164). Age (≥66 years old), MTV (≥87.1 mL) of cervical tumor and PET/CT-defined para-aortic lymph node (PALN) metastasis were independent significant adverse predictors for cancer-specific survival (CSS) ( P 〈 0.001, P=0.002, and P=0.033, respectively). Counting each risk predictor as score one, patients with risk score sum 0, 1, 2, 3 had a 5-year CSS of 85.8%, 68.5%, 29.7%, and 0%, respectively ( P 〈 0.001). Conclusions: Age, cervical tumor MTV and PET/CT-defined PALN metastasis are independent risk predictors in locally advanced cervical SCC. Patients with risk score sum 0 may receive CCRT with single-agent cisplatin, while patients with risk score sum ≥1 may consider receiving novel combination therapies or entering clinical trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 24 ( 2007-08-20), p. 3628-3634
    Abstract: Our aim was to evaluate the prognostic significance of human papillomavirus (HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center. Patients and Methods Consecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction (PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types. Results A total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting (P 〈 .0001) and relapse-predicting (P 〈 .0001) models classifying three risk groups (low, intermediate, and high risk) were constructed and endorsed by internal validation. Conclusion The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21621-e21621
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21621-e21621
    Abstract: e21621 Background: EGFR mutations are heterogenous but all carry the same weight in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Methods: Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 256 patients were included with a median overall survival (OS) of 17.2months. Patients with Lung-molGPA scores of 1, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 5.9,11.5, 17.2, and 23.4months, respectively (p 〈 0.001). In multivariate analysis of OS, only age (³70 versus 〈 70 years, HR:1.71, 95% CI:1.25-2.35, p 〈 0.001), KPS ( 〈 70 versus ³70, HR:1.71, 95% CI:1.26-2.31, p 〈 0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p = 0.037) remained statistically significant. In patients with a Lung-molGPA score £2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.9vs 12.8vs 4.5months, p = 0.021) and prognostic implications (Leu858Arg versus exon 19 deletions, HR: 1.85, 95% CI: 1.20-2.84, p = 0.005; other versus exon 19 deletions, HR:2.18, 95% CI:1.11-4.26, p = 0.023). Conclusions: Different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13588-e13588
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13588-e13588
    Abstract: e13588 Background: BM represent a common problem in EGFR-mutated lung adenocarcinoma. The updated Lung-molGPA elucidates the survival in patients with non-small-cell lung cancer and BM by incorporating the effect of EGFR gene alterations. However, the nature history and differences of prognostic implication between common and uncommon EGFR mutations remain unsolved. Methods: By retrospective analysis of Chang-Gung Research Database (CGRD), patients with EGFR-mutated lung adenocarcinoma and BM were included into analysis of PFS and OS. EGFR mutations were categorized into exon 19 deletions (Del19), exon 21 Leu858Arg substitution (L858R) and uncommon mutations. Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models was performed to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI). The p-value was set to be statistically significant at 0.05 or less. Results: From April 1, 2014 to June 30, 2015, 269 out of 818 patients with EGFR-mutated lung adenocarcinoma and BM were included, of which 115 patients with Del19, 131 patients with L858R, and 23 patients with uncommon EGFR mutations. The baseline characteristics were balanced in age, gender, KPS, ECM, number of BM, and timing of BM. In comparison with those with L858R, uncommon mutations is a poor prognostic factor for PFS (HR 2.24, 95% CI: 1.34-3.75, p = 0.002). The median PFS of Del 19, L858R, and uncommon EGFR mutations were 10.4, 10.0, and 3.2 months, respectively (log-rank p = 0.03). Besides, the median OS of Del 19, L858R, and uncommon EGFR mutations were 18.1, 17.4, and 12.5 months, respectively (log-rank p = 0.05). In comparison with those treated with gefitinib, afatinib treatment is a good prognostic factor for PFS and OS (PFS, HR 0.57, 95% CI: 0.35-0.94, p = 0.03; OS, HR 0.48, 95% CI: 0.26-0.91, p = 0.03). The median PFS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 11.0, 8.5, and 10.3, respectively (log-rank p = 0.63). In addition, the median OS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 18.7, 15.2, and 18.2 months, respectively (log-rank p = 0.50). Conclusions: Among patients with EGFR-mutated adenocarcinoma, common and uncommon EGFR mutations have distinct natural history and prognostic implications in patients with BM.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e15137-e15137
    Abstract: e15137 Background: ABT-301 (previously known as MPT0E028) is a novel, oral pan-histone deacetylases (HDAC) inhibitor with potent inhibitory activity for HDAC 1, 2, 3 (class I), HDAC 6, 10 (class IIb), modest activity for HDAC 8 (class I) and HDAC 11 (class IV), but no activity for HDAC 4, 5, 7, 9 (class IIa). Preclinical studies showed that ABT-301 had a stronger apoptotic activity and inhibited HDAC activity more potently than vorinostat. ABT-301 exerts antitumor activity as a monotherapy in human colorectal cancer and B-cell lymphoma xenografts and synergistic antitumor activity with immune checkpoint inhibitor in CT26 syngeneic tumor model. Methods: This was a 3+3 Phase 1 dose escalation study to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetic (PK) /pharmacodynamic (PD) profiles for the ABT-301 in patients with locally advanced or metastatic solid cancers. 5 cohorts of 3 or 6 patients received ABT-301 once daily at gradually escalating doses starting from 50 mg. Results: 23 subjects (6 sarcomas and 17 carcinomas) were treated at 5 dose levels (3 at 50, 100, and 250 mg respectively, 6 at 150 mg, and 8 at 200 mg). Cycle 1 DLTs occurred in 5 subjects: 1 at 50 mg (G3 mucositis); 2 at 200 mg (G3 abdominal pain and G4 thrombocytopenia); 2 at 250 mg (G3 vomiting and G4 thrombocytopenia). The MTD was 150 mg. The most common treatment-related adverse events were thrombocytopenia (44%), anemia (18%), nausea (61%), vomiting (44%), anorexia (22%), hyperglycemia (22%), fatigue (18%), and mucositis (18%), which were generally G1 to G2 in severity. No cardiac abnormalities were observed. 1 had a partial response (PR), and 8 achieved SD, resulting in a disease control rate (DCR) of 39%. The PR (a patient with eccrine ductal carcinoma) lasted 24 weeks whereas 5/8 SD patients achieved a sustained condition of 16 to 53 weeks (hepatocellular carcinoma, 53 w; thymic cancer, 49 w; salivary gland carcinoma, 27 w; endometrial stromal carcinoma, 25 w; renal cell carcinoma, 16 w). DCR for 9 patients at MTD was 78% (7/9; 1 PR and 6 SD). Plasma PK showed a dose-dependent increase in ABT-301 exposure. Cmax is 5.5 µM and AUC 0-inf is 11.5 µM*h at 150 mg. Increased acetylated histone 3 was observed across all cohorts. Conclusions: ABT-301 was well-tolerated at a daily dose of up to 150 mg and demonstrated objective responses and long-term SD across multiple tumor types at MTD. The safety profile of ABT-301 was superior to known HDAC inhibitors with only predictable HDAC inhibitor-related toxicities observed but no cardiac toxicity, neutropenia, nor lymphopenia elicited. Non-clinical and clinical results suggested the potential clinical development of ABT-301 in combination with myelosuppressive agents and immunotherapies. Phase 2 studies combining PD-1/PD-L1 blockade are being designed. Clinical trial information: NCT02350868 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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