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  • American Society of Clinical Oncology (ASCO)  (5)
  • 1
    Online Resource
    Online Resource
    Conformal Radiation Therapy for Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma, and Observation for Completely Resected, Supratentorial Ependymoma
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 12 ( 2019-04-20), p. 974-983
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 12 ( 2019-04-20), p. 974-983
    Abstract: The Children’s Oncology Group trial ACNS0121 estimated event-free survival (EFS) and overall survival for children with intracranial ependymoma treated with surgery, radiation therapy, and—selectively—with chemotherapy. Treatment was administered according to tumor location, histologic grade, and extent of resection. The impacts of histologic grade, focal copy number gain on chromosome 1q, and DNA methylation profiles were studied for those undergoing surgery and immediate postoperative conformal radiation therapy (CRT). METHODS ACNS0121 included 356 newly diagnosed patients (ages 1 to 21 years). Patients with classic supratentorial ependymoma were observed after gross total resection (GTR). Those undergoing subtotal resection received chemotherapy, second surgery, and CRT. The remaining patients received immediate postoperative CRT after near-total resection or GTR. CRT was administered with a 1.0-cm clinical target volume margin. The cumulative total dose was 59.4 Gy, except for patients who underwent GTR and were younger than age 18 months (who received 54 Gy). Patients were enrolled between October 2003 and September 2007 and were observed for 5 years. Supratentorial tumors were evaluated for RELA fusion; infratentorial tumors, for chromosome 1q gain. Classification of posterior fossa groups A and B was made by methylation profiles. RESULTS The 5-year EFS rates were 61.4% (95% CI, 34.5% to 89.6%), 37.2% (95% CI, 24.8% to 49.6%), and 68.5% (95% CI, 62.8% to 74.2%) for observation, subtotal resection, and near-total resection/GTR groups given immediate postoperative CRT, respectively. The 5-year EFS rates differed significantly by tumor grade ( P = .0044) but not by age, location, RELA fusion status, or posterior fossa A/posterior fossa B grouping. EFS was higher for patients with infratentorial tumors without 1q gain than with 1q gain (82.8% [95% CI, 74.4% to 91.2%] v 47.4% [95% CI, 26.0% to 68.8%] ; P = .0013). CONCLUSION The EFS for patients with ependymoma younger than 3 years of age who received immediate postoperative CRT and for older patients is similar. Irradiation should remain the mainstay of care for most subtypes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.18.01765
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Circulating tumor DNA (ctDNA) and late recurrence in high-risk, hormone receptor–positive, HER2-negative breast cancer (CHiRP).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 103-103
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 103-103
    Abstract: 103 Background: Hormone receptor–positive breast cancer (HR+ BC) is the most common cause of BC-related death. Over half of metastatic recurrences occur ≥ 5 years (y) from diagnosis. Detection of minimal residual disease (MRD) via circulating tumor DNA (ctDNA) can identify cancer recurrence months to years in advance and may be an important tool to guide therapy. Little is known about ctDNA in the late adjuvant setting. We investigated ctDNA dynamics and clinical outcomes in pts ≥ 5 y from diagnosis of high-risk early-stage HR+ BC. Methods: Patients with high-risk HR+ BC (T3-4 or N2-3 or T1 with 3+ lymph nodes, or T2N1 [and Oncotype RS ≥ 26; grade 3; or Ki-67 ≥ 20%]) with no evidence of recurrence 5 y after diagnosis were prospectively identified and consented. Plasma samples were collected at time of consent and at routine visits every 6-12 mos. Whole-exome sequencing (WES) was performed on primary tumor tissue to identify somatic mutations and design for each patient a RaDaR assay, a tumor-informed liquid biopsy test to detect plasma ctDNA. Per current practice standards, pts did not undergo regular surveillance imaging. All pts were followed for development of local and/or distant metastatic recurrence, as determined by their clinical provider. Results: Of 103 pts enrolled, 85 had sufficient tumor tissue, and 83 pts had successful WES. Personalized RaDaR assays were designed targeting 12-51 variants (median, 36), and used to test 219 plasma samples from 83 pts. The number of plasma samples per patient ranged from 1-7 (median, 2). 57 pts (68.7%) had stage 3 disease, and most (75, 90.4%) received curative-intent chemotherapy. All pts received endocrine therapy (ET). 39 (47%) remained on adjuvant ET at time of last follow up. Of 44 pts who completed adjuvant ET, 41 (93.2%) received 〉 5 y of treatment. Time from diagnosis to first sample ranged from 4.9-20 y (median, 8.4 y). Median (range) follow up was 10.2 (6.7-22.3) y from diagnosis and 1.8 (0-3.6) y from first sample. 5 pts (6%) developed distant metastatic recurrence and 2 pts (2.4%) had locoregional recurrence. 4/83 (5%) pts were MRD+ at study entry and 8/83 (10%) pts were MRD+ at any time point. 5/5 (100%) pts with metastatic recurrence were MRD+, with ctDNA lead times up to 37.6 mos. ctDNA was detected at tumor fractions of 0.0027-26.84% (median, 0.396%). 2/8 (25%) MRD+ pts had not had clinical recurrence at latest follow up, one with no follow up since detection and one 15.4 mos from ctDNA detection (with ctDNA levels 0.045% and 26.84%). Conclusions: Here we report—to our knowledge—the first data on ctDNA detection in late adjuvant HR+ BC. 10% of pts had MRD at ≥ 5 y from diagnosis. ctDNA analysis identified MRD in all cases of distant recurrence. ctDNA was detected in 2 pts who have not yet experienced recurrence. Longer follow up is necessary for these pts at high risk. Additional studies will determine if ctDNA-guided intervention can alter clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.103
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Genome-wide copy number analysis of cell-free DNA from patients with chemotherapy-resistant metastatic triple-negative breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 1092-1092
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1092-1092
    Abstract: 1092 Background: Triple-negative breast cancer (TNBC) is a poor prognosis breast cancer subset characterized by relatively few mutations but extensive copy number alterations (CNAs). Cell-free DNA (cfDNA) offers the potential to overcome infrequent tumor biopsies in metastatic TNBC (mTNBC) and interrogate the genomics of chemotherapy resistance. Methods: 506 archival or fresh plasma samples were identified from 164 patients with mTNBC who had previously received chemotherapy. We performed low coverage sequencing to determine genome-wide copy number and estimate ‘tumor fraction’ of cfDNA (TFx). In patient samples with TFx 〉 10%, we identified regions that were significantly gained or lost using GISTIC2.0. We compared CNAs of mTNBCs with primary TNBCs from a publicly-available dataset, METABRIC (TNBC n=277). Results: We successfully obtained high quality, low coverage whole genome sequencing data for 478 (94.5%) plasma samples from 158 patients, with 1 to 14 samples per patient. Archival samples had significantly higher average cfDNA per mL plasma and TFx than fresh samples, potentially due to later average line of therapy. Average TFx of first blood draw was significantly higher in patients with liver metastases (TFx 28.3% vs. 14.4%, p=1.1e-7). 101/158 patients (63.9%) had at least one sample with TFx 〉 10%, our threshold for high confidence CNA calls. Most alterations significantly enriched in chemotherapy-resistant mTNBCs were chromosomal gains, including NOTCH2 and ERCC1. Median overall survival from time of first blood draw was 9 months, and TFx was highly correlated independent of metastatic line of therapy, age at metastatic diagnosis, BRCA status, and primary stage: adjusted hazard ratio between 4 th and 1 st quartiles = 4.29 (95% CI 1.66-11.1; p=0.0008). Conclusions: It is feasible to perform genome-level copy number analysis from cfDNA in both archival and fresh samples from patients with mTNBC. Copy number alterations enriched in mTNBC may have implications in the understanding of metastasis, therapeutic resistance, and novel therapeutic targets. ‘Tumor fraction’ of cfDNA is correlated with overall survival and may be an independent prognostic marker in mTNBC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.1092
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Patterns of distant metastases in HPV-positive head and neck squamous cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. 6071-6071
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 6071-6071
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.6071
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 5
    Online Resource
    Online Resource
    Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 10 ( 2011-04-01), p. 1239-1246
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 10 ( 2011-04-01), p. 1239-1246
    Abstract: To assess the frequency and type of oncogenic BRAF mutations in metastatic melanoma and correlate BRAF status with clinicopathologic features and outcome. Patients and Methods Consecutive BRAF-tested Australian patients with metastatic melanoma (n = 197) were observed prospectively. A comprehensive range of clinicopathologic variables were correlated with BRAF mutation status, and a survival analysis was conducted. Results Forty-eight percent of patients had a BRAF mutation; 70 patients (74%) had V600E, 19 (20%) had V600K, and six (6%) had other genotypes. Other than age at diagnosis of distant metastasis (median age, 56 v 63 years for BRAF-mutant v BRAF wild-type patients, respectively; P 〈 .001), there was no significant difference in clinical features of patients with metastatic melanoma by mutation status. Features of the antecedent primary melanoma significantly associated with a BRAF mutation (P 〈 .05) were histopathologic subtype, presence of mitoses, single or occult primary melanoma, truncal location, and age at diagnosis of primary tumor ≤ 50 years. The interval from diagnosis of first-ever melanoma to distant metastasis was not significantly different between BRAF-mutant and BRAF wild-type patients; however, the median survival of patients with newly diagnosed metastatic melanoma was 5.7 months for BRAF-mutant patients not treated with a BRAF inhibitor, 8.5 months for BRAF wild-type patients, and not reached for BRAF-mutant patients treated with a BRAF inhibitor. Conclusion V600K mutations comprised 20% of BRAF mutations. Characteristics of the antecedent primary melanoma and age at diagnosis differed in BRAF-mutant and BRAF wild-type patients. The presence of mutant BRAF had no impact on the disease-free interval from diagnosis of first-ever melanoma to first distant metastasis; however, it may have impacted survival thereafter.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2010.32.4327
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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