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  • American Society of Clinical Oncology (ASCO)  (17)
  • 1
    Online Resource
    Online Resource
    Overall response rate as a surrogate of progression-free survival with molecular targeted agents: A meta-analysis of phase III trials in advanced non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e19142-e19142
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e19142-e19142
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e19142
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Long-term outcomes of a pilot study on highly hypofractionated intensity-modulated radiation therapy over three weeks for localized prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 259-259
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 259-259
    Abstract: 259 Background: A number of reports have been published on both moderately hypofractionated intensity-modulated radiation therapy (IMRT) for localized prostate cancers using 2.4 – 3.4 Gy per fraction over 4 – 6 weeks, and ultrahypofractionation over 1 – 2 weeks using 6 Gy or more per fraction. However, long-term outcomes have sparsely been reported using doses between these two fractionations (3.4 – 6.0 Gy per fraction) over 2 – 3 weeks (high hypofractionation). Therefore, we performed a pilot study of highly hypofractionated IMRT in 15 fractions using 3.6 Gy per fraction over 3 weeks for localized prostate cancer. We now report the long-term outcomes of the study. Methods: Twenty-five patients with low- to intermediate-risk prostate cancer were enrolled in this prospective study from April 2014 to September 2015. Fifty-four Gy in 15 fractions (3.6 Gy per fraction) was delivered over three weeks using IMRT with CBCT-based image guidance without intraprostatic fiducial markers. Based on an estimated alpha/beta ratio for prostate cancer of 1.5 Gy, the EQD2 was 78.7 Gy for the present dose fractionation. Neoadjuvant hormonal therapy (HT) was administered to intermediate-risk patients for 4 – 8 months, but was not mandatory in patients with low-risk disease. Adjuvant HT was not provided for any patient. Biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), overall survival (OS), and the cumulative incidence rate of late toxicities were analyzed using the Kaplan Meier method. Results: Twenty-four patients were treated with highly hypofractionated IMRT, except one case switched to conventionally fractionated IMRT because we could not meet the dose constraint of the small bowel in treatment planning. Among the 24 patients, 17 % had low-risk, and 83% had intermediate-risk disease. Neoadjuvant HT was administered to 23 patients, and the median duration of HT was 5.3 months. The median follow-up period was 77 months (range, 57–87 months). BRFS, CRFS, and OS were 91.7%, 95.8% and 95.8% at 5 years, and 87.5%, 86.3% and 95.8% at 7 years, respectively. No patient died of prostate cancer, but one patient died due to the other cancer. Neither grade ≥2 late gastrointestinal toxicity nor ≥3 late genitourinary toxicity was observed. Grade 2 late genitourinary toxicity did not occur during the first 4 years, but was developed in 5 patients after more than 4-year follow-up. The cumulative incidence rate was 12.9% and 22.8% at 5 and 7 years, respectively. Conclusions: Highly hypofractionated IMRT delivering 54 Gy in 15 fractions over 3 weeks for prostate cancer without intraprostatic fiducial markers demonstrates favorable oncological outcomes with no severe complications. This treatment approach could be a possible alternative of moderate hypofractionation, although further studies will be mandatory.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.259
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 3
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    Online Resource
    Long-term outcomes of intensity-modulated radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with non-metastatic prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 6_suppl ( 2018-02-20), p. 49-49
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 49-49
    Abstract: 49 Background: This study aimed to evaluate long-term outcomes of intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) hormonal therapy (HT) in Japanese patients with non-metastatic prostate cancer (NMPC). Methods: We retrospectively analyzed the data of 485 patients with T1-T4N0M0 adenocarcinoma of the prostate treated with IMRT combined with NA-HT. Of these patients, 32, 113, 250, and 90 patients were categorized into the low-, intermediate-, high-, and very high-risk groups, respectively, according to the NCCN risk classification. NA-HT was administered over a median duration of 6 months. In principle, 74 or 78 Gy in 2 Gy per-fraction were delivered to the prostate and seminal vesicles according to the risk. We did not administer adjuvant HT (A-HT) for any patient following the completion of IMRT. Salvage HT (S-HT) commenced when prostate-specific antigen (PSA) values exceeded 4 ng/mL. Results: The median follow-up period was 103.4 months, and the median PSA value at the initiation of S-HT was 5.1 ng/mL. In the low-risk group, the 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival, and S-HT-free (SHTF) rates were 89.7%, 100.0%, 100.0%, and 96.7%, respectively. Those were 83.7%, 100.0%, 96.0%, and 94.3% for the intermediate-risk group, 64.5%, 97.8%, 87.0%, and 79.4% for the high-risk group, and 47.7%, 96.6%, 89.7%, and 53.3% for the very high-risk group, respectively. The estimated 8-year cumulative incidence rates of late gastrointestinal and genitourinary (grades 2–3) toxicity were 7.2% and 21.8%, respectively. We observed no grade 4 or higher toxicity. Conclusions: High-dose IMRT, combined with NA-HT and without A-HT under the early S-HT policy, achieved excellent survival outcomes with acceptable morbidities for a Japanese cohort with NMPC. Moreover, especially for high, and very high-risk patients, this approach could be a viable alternative to the uniform provision of long-term A-HT because more than the half of the patients maintained SHTF status over a period of 8-year after IMRT. Prospective trials are warranted to validate the findings of this study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.6_suppl.49
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Outcomes of high-dose whole pelvic simultaneous integrated boost IMRT in patients with pelvic lymph node-positive prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 192-192
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 192-192
    Abstract: 192 Background: Managements of prostate cancer patients with positive pelvic lymph node (N1M0) have been very challenging. We evaluated the outcomes of high-dose whole pelvic (WP) intensity-modulated radiation therapy (IMRT) by using the simultaneous integrated boost (SIB) technique, combined with long-term androgen deprivation therapy (ADT). Methods: Between May 2005 and November 2013, 52 patients with T2a-T4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Pelvic lymph node metastases were clinically diagnosed based on the following criteria; depicted swollen lymph nodes on diagnostic imaging associated with subsequent shrinkage in size on a follow-up imaging after neoadjuvant ADT (NA-ADT). The median age and initial PSA value were 66 years old (range: 52–79) and 29.7 ng/ml (4.8–251.9), respectively. NA-ADT (median: 8 months, range: 5–20) was given in all cases. SIB WP-IMRT was designed to simultaneously deliver 78 Gy, 66.3 Gy, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes, and the pelvic lymph node region, respectively. Adjuvant ADT (A-ADT) was given in all patients except for one case who developed severe adverse events during NA-ADT. In 9 patients, permanent A-ADT was given due to castration after IMRT (n = 2) and development to castration resistant status during A-ADT (n = 7). The median duration of A-ADT was 24 months (range: 7–71) in the remaining 42 patients. Results: The median follow-up period was 69 months (range: 12–136). Biochemical relapse-free survival rate based on the Phoenix definition and distant metastasis-free survival rates at 5 years were 69% (95% CI = 54%–80%) and 78% (95% CI = 64%–87%), respectively. Overall survival and prostate cancer-specific survival rates at 5 years were 88% (95% CI = 74–94%) and 92% (95% CI = 79–97%), respectively. Loco-regional recurrence was not observed. 5-year cumulative incidence rates of grade 2-3 late GU and GI toxicities were both 2%. No grade 4 acute or late toxicity was observed. Conclusions: High-dose WP SIB-IMRT to patients with N1M0 prostate cancer seems promising, and warrants future prospective studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.192
    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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  • 5
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    Online Resource
    Acute Lung Injury With Alveolar Hemorrhage As Adverse Drug Reaction Related to Crizotinib
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 26 ( 2013-09-10), p. e417-e419
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 26 ( 2013-09-10), p. e417-e419
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2012.47.1110
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 6
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    Pharmacogenetic study of Japanese patients with advanced nonsquamous non-small cell lung cancer treated with pemetrexed plus cisplatin.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19050-e19050
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19050-e19050
    Abstract: e19050 Background: Pemetrexed (PEM) inhibits multiple enzymes in the folate (F) pathway. Several studies show that genetic polymorphisms in these enzymes influence the efficacy and toxicity of PEM. We aimed to investigate the relationship between genetic polymorphisms associated with the F pathway and clinical outcomes of Japanese patients with advanced non-squamous non-small cell lung cancer (NSQ-NSCLC) treated with PEM plus cisplatin (CIS). Methods: We analyzed 38 polymorphisms in 15 genes associated with the F pathway in NSQ-NSCLC patients treated with PEM plus CIS: ABCC11, ADA, ATIC, CBS, DHFR, ERCC1, FPGS, GGH, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS. These polymorphisms were compared with clinical outcomes such as response, toxicity, and progression-free survival (PFS) using Pearson’s χ 2 test and the log-rank test. Results: All 56 patients were Japanese, with a median age of 62 years; 57.1% were male, 96.4% had an Eastern Cooperative Oncology Group Performance Status of 0–1, 96.4% had stage IV disease, and 94.6% had adenocarcinoma. The response rate, disease control rate, and median PFS were 32.2%, 78.6%, and 4.7 months, respectively. Of the 38 polymorphisms tested, none were associated with response or toxicity, but 2 single nucleotide polymorphisms (SNPs) (in the gamma-glutamyl hydrolase [GGH 452C 〉 T] and methionine synthase [MTR 2756A 〉 G] genes) were significantly associated with PFS. Patients harboring the GGH-C452C variant had significantly longer PFS (5.6 vs 2.8 months; p 〈 0.0001) than those with the C452T or T452T variants. Further, patients harboring the MTR-A2756A variant had significantly longer PFS (5.3 vs 3.7 months; p = 0.036) than those with the A2756G variant. In addition, among patients with the GGH-C452C variant, those harboring the MTR-A2756A variant had significantly longer PFS (5.9 vs 4.3 months; p = 0.044) than those with the A2756G variant. Conclusions: SNPs in GGH and MTR seem to predict differences in PFS in NSQ-NSCLC patients treated with PEM plus CIS, and a combination of these 2 SNPs may predict differences in PFS more accurately. These results should be validated in larger, adequately designed prospective studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e19050
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 7
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    Assessment of preoperative liver function in patients with hepatocellular carcinoma: The albumin-indocyanine green evaluation (ALICE) grade.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 4066-4066
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 4066-4066
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.4066
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Multiplexed genetic analysis of malignant pleural mesothelioma and the relationship to clinical outcome.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 7582-7582
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 7582-7582
    Abstract: 7582 Background: Genotype-based stratification is essential to improve cancer treatment. We have developed a multiplexed tumor genotyping panel for detecting gene alterations relevant to molecular targeted therapies. We applied this genotyping panel to malignant pleural mesothelioma (MPM) and evaluate the relationship between clinical outcome and gene alterations. Methods: Surgical specimens and tumor biopsies from 40 patients with MPM were collected from 2003 to 2012. Pathological diagnoses were confirmed by immunohistochemistry in addition to HE stain. 37 patients were genotyped with multiplexed tumor genotyping panel developed to assess 9 gene mutations (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2) and 5 genes amplifications (EGFR, MET, PIK3CA, FGFR1 and FGFR2) using pyrosequencing plus capillary electrophoresis, and qRT-PCR, respectively. Other 3 patients were analyzed by ultra-deep targeted sequencing with next generation sequencer. 5 fusion genes (EML4-ALK, CD74-ROS1, SLC34A2-ROS1, KIF5B-RET and CCDC6-RET) were tested in 2 patients with fresh frozen specimens. Results: Gene alterations were detected in 6 patients (Table shown below). These patients harboring gene alterations showed poorer survival than the patients in whom gene alterations were not detected (median survival time (MST): 583 vs 164 days, log-lank: p=0.009). Moreover, the patients with PIK3CA amplification/mutation showed poorer survival than the patients without PIK3CA amplification/mutation (MST: 583 vs 103 days, log-lank: p=0.031). Conclusions: Gene alterations which could be a target for molecular targeted therapy were detected in MPM. Especially, PIK3CA pathway is a potential target. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.7582
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Online Resource
    Pathological images machine learning and prediction of long-term efficacy for immunotherapy in small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 8578-8578
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 8578-8578
    Abstract: 8578 Background: In development of effective treatment such as immune checkpoint inhibitors (ICIs) among patients with small-cell lung cancer (SCLC), the absence of biomarkers is critical. Tumor-infiltrating lymphocytes are the main activator of antitumor immunity and could be a promising biomarker if TIL can be objectively assessed throughout the whole tumor immune microenvironment (TIME). To evaluate TIME, pathological assessment is one of the easiest ways. Recently, several studies showed that machine learning analysis can assess type of lymphocytes and their localization in pathological images. Here, we aimed to develop a novel biomarker to predict efficacy of ICI in SCLC using machine learning of pathological images. Methods: This study was a biomarker analysis of the APOLLO study which was 32-centered, prospective cohort study of patients with extensive-stage SCLC who received chemo-immunotherapy as the first-line treatment between September 2019 and September 2020. The patient who can provide sufficient tumor tissue sample from the primary tumor were enrolled. We trained a classifier which predicts 365-day progression-free survival (PFS) by all three types of pathological images (hematoxylin and eosin, programmed death-ligand 1, and CD8_FoxP3) and patient information, and developed the patient information model, pathological image model, and combination model. We used the area under the curves (AUC) to evaluate the machine learning models. Results: Of 78 patients, the median age was 78 (interquartile range, 48-87), 65 patients (83%) were male, 67 patients (86%) had a performance status of 0 or 1, and three patients (3.8%) treated with steroid therapy. Among all patients, the median PFS and the 365-day PFS rates were 145 days and 10.3%. The mean AUC of these models was 0.789 (range, 0.571-0.982) in the patient information model, 0.782 (range, 0.750-0.911) in the pathological image model, and 0.868 (range, 0.786-0.929) in the combination model, respectively. According to the median precision model, the median PFS was longer for the high efficacy group than the low efficacy group (the patient information model; hazard ratio (HR) 0.468, 95% confidence intervals (CI) 0.287-0.762. the pathological image model; HR 0.334, 95%CI 0.117-0.628. the combination model; HR 0.353, 95%CI 0.195-0.637). Conclusions: Using machine learning by pathological images, we could predict the efficacy of immunotherapy in SCLC. This study demonstrated the potential of machine learning to help the biomarker development in SCLC by assessing TIME. Clinical trial information: UMIN000038064 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.8578
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Dual inhibition of PARP and ATR induces homologous recombination repair deficiency and leads to synthetic lethality in prostate cancer with CDK12 alteration.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e17042-e17042
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e17042-e17042
    Abstract: e17042 Background: CDK12 is considered as a gene involved in homologous recombination repair (HRR); however, recent clinical trials have shown poor benefit of poly(ADP-ribose) polymerase(PARP) inhibitors in prostate cancer (PCa) patients with CDK12 alterations. Since CDK12 is the third most commonly altered gene in the HRR pathway in PCa, development of a new treatment strategy is urgently needed. Methods: To understand the biological consequence of CDK12 alteration, CDK12 was knocked out in LNCaP using CRISPR-Cas9 system to generate CDK12KO cells. Cell growth and cell cycle were evaluated as well as HRR efficiency. Downstream genes were evaluated by RT-PCR and western blots. Combination therapy by a PARP inhibitor and ATR inhibitors were tested using two lines of patient derived xenografts (PDX) established from tissues of patients with deleterious CDK12 variants. Three different ATR inhibitors were tested to confirm reproducibility. Results: In LNCaP, CDK12 knockout enhanced cell cycle progression until the M phase, however, cell cycle was stalled at the M phase with accumulation chromosomal aberration, suggesting that rapidly progressive CDK12 altered tumors clinically encountered harbor a mechanism of escaping the M phase checkpoint without DNA repair. γH2AX was accumulated in CDK12KO after treatment with CPT11, consistent with impaired HRR in CDK12 KO cells. Analysis of HRR associated genes showed that in PCa, CDK12 knockout leads to transcriptional downregulation of ATM but not the other HRR associated genes. Expression patterns of downstream genes after double strand break (DSB) induction in CDK12 and ATM knockout cells suggested that in PCa, CDK12 regulates HRR through regulation of ATM. Since synthetic lethality of PARP and ATR inhibition has been reported in ATM deficient PCa, 2 PDX lines with CDK12 alterations were administered the combination therapy. Tumor growth suppression and accumulation of γH2AX in tumor tissue was observed when treated by the combination therapy, but not with either drug alone. Either drug alone or in combination did not affect the growth of a PDX established from a tissue of a patient with wild-type CDK12. Conclusions: In PCa, CDK12 acts through transcriptional regulation of ATM, and combination treatment with PARP inhibitor and ATR inhibitor could be a potential treatment strategy in PCa with CDK12 alteration.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e17042
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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