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  1. Article ; Online: Towards Data Driven RT Prescription: Integrating Genomics into RT Clinical Practice.

    Torres-Roca, Javier F / Grass, G Daniel / Scott, Jacob G / Eschrich, Steven A

    Seminars in radiation oncology

    2023  Volume 33, Issue 3, Page(s) 221–231

    Abstract: The genomic era has significantly changed the practice of clinical oncology. The use of genomic-based molecular diagnostics including prognostic genomic signatures and new-generation sequencing has become routine for clinical decisions regarding ... ...

    Abstract The genomic era has significantly changed the practice of clinical oncology. The use of genomic-based molecular diagnostics including prognostic genomic signatures and new-generation sequencing has become routine for clinical decisions regarding cytotoxic chemotherapy, targeted agents and immunotherapy. In contrast, clinical decisions regarding radiation therapy (RT) remain uninformed about the genomic heterogeneity of tumors. In this review, we discuss the clinical opportunity to utilize genomics to optimize RT dose. Although from the technical perspective, RT has been moving towards a data-driven approach, RT prescription dose is still based on a one-size-fits all approach, with most RT dose based on cancer diagnosis and stage. This approach is in direct conflict with the realization that tumors are biologically heterogeneous, and that cancer is not a single disease. Here, we discuss how genomics can be integrated into RT prescription dose, the clinical potential for this approach and how genomic-optimization of RT dose could lead to new understanding of the clinical benefit of RT.
    MeSH term(s) Humans ; Neoplasms/genetics ; Neoplasms/radiotherapy ; Neoplasms/pathology ; Medical Oncology ; Antineoplastic Agents ; Prognosis ; Genomics
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2023-06-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1146999-7
    ISSN 1532-9461 ; 1053-4296
    ISSN (online) 1532-9461
    ISSN 1053-4296
    DOI 10.1016/j.semradonc.2023.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Letter Response.

    Sedor, Geoffrey / Scott, Jacob G / Kattan, Michael W / Torres-Roca, Javier F

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2021  Volume 16, Issue 5, Page(s) e28–e29

    MeSH term(s) Genomics ; Humans ; Lung Neoplasms ; Prescriptions ; Radiation Tolerance
    Language English
    Publishing date 2021-03-31
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2021.02.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Radiotherapy with genomic-adjusted radiation dose - Authors' reply.

    Scott, Jacob G / Sedor, Geoffrey / Scarborough, Jessica A / Kattan, Michael W / Torres-Roca, Javier F

    The Lancet. Oncology

    2021  Volume 22, Issue 11, Page(s) e470–e471

    MeSH term(s) Dose Fractionation, Radiation ; Genomics ; Humans ; Radiation Dosage ; Radiation Oncology
    Language English
    Publishing date 2021-10-08
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(21)00601-X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Response to: Noncancer Cells in Tumor Samples May Bias the Predictive Genomically Adjusted Radiation Dose.

    Grass, G Daniel / Scott, Jacob G / Sedor, Geoffrey / Kattan, Michael W / Torres-Roca, Javier F

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2021  Volume 16, Issue 6, Page(s) e48–e49

    MeSH term(s) Dose-Response Relationship, Radiation ; Humans ; Lung Neoplasms
    Language English
    Publishing date 2021-05-25
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2021.03.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Changing Radiotherapy Paradigms in Penile Cancer.

    Johnstone, Peter A S / Spiess, Philippe E / Sedor, Geoff / Grass, G Daniel / Yamoah, Kosj / Scott, Jacob G / Torres-Roca, Javier F

    European urology open science

    2022  Volume 36, Page(s) 47–48

    Abstract: Radiation therapy (RT) has not been prominent in the treatment of penile cancer because of poorly reproducible results when used in the adjuvant setting. A genomic signature has recently been described that assays radiosensitivity of tumors and informs ... ...

    Abstract Radiation therapy (RT) has not been prominent in the treatment of penile cancer because of poorly reproducible results when used in the adjuvant setting. A genomic signature has recently been described that assays radiosensitivity of tumors and informs radiotherapy doses in these cases. Clinical validation in more than 1600 patients demonstrated associations with both overall survival and time to first recurrence. In addition, the signature predicted and quantified the therapeutic benefit of RT for each individual patient. Since penile cancer patients were not part of this analysis, we applied the model to patients with primary and nodal penile cancer tissue and clinical outcomes.
    Language English
    Publishing date 2022-01-04
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-1683
    ISSN (online) 2666-1683
    DOI 10.1016/j.euros.2021.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: A molecular assay of tumor radiosensitivity: a roadmap towards biology-based personalized radiation therapy.

    Torres-Roca, Javier F

    Personalized medicine

    2012  Volume 9, Issue 5, Page(s) 547–557

    Abstract: The last two decades have seen technological developments that have led to more accurate delivery of radiation therapy (RT), which has resulted in clinical gains in many solid tumors. However, a fundamental question and perhaps the next major hurdle is ... ...

    Abstract The last two decades have seen technological developments that have led to more accurate delivery of radiation therapy (RT), which has resulted in clinical gains in many solid tumors. However, a fundamental question and perhaps the next major hurdle is whether biological strategies can be developed to further enhance the effectiveness and efficiency of RT. This article addresses the development of a novel genomics-based molecular assay to predict tumor radiosensitivity, and proposes that this assay may prove pivotal in the development of biologically guided RT.
    Language English
    Publishing date 2012-08-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2299146-3
    ISSN 1744-828X ; 1741-0541
    ISSN (online) 1744-828X
    ISSN 1741-0541
    DOI 10.2217/pme.12.55
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Genomic-adjusted radiation dose - Authors' reply.

    Scott, Jacob G / Harrison, Louis B / Torres-Roca, Javier F

    The Lancet. Oncology

    2017  Volume 18, Issue 3, Page(s) e129

    MeSH term(s) Genomics ; Radiation Dosage
    Language English
    Publishing date 2017-03-02
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(17)30119-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genomic biomarkers for precision radiation medicine - Authors' reply.

    Scott, Jacob G / Harrison, Louis B / Torres-Roca, Javier F

    The Lancet. Oncology

    2017  Volume 18, Issue 5, Page(s) e239

    MeSH term(s) Biomarkers ; Genomics ; Precision Medicine ; Research
    Chemical Substances Biomarkers
    Language English
    Publishing date 2017-05-04
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(17)30264-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease.

    Ahmed, Kamran A / Torres-Roca, Javier F

    Cancer control : journal of the Moffitt Cancer Center

    2016  Volume 23, Issue 1, Page(s) 21–29

    Abstract: Background: The treatment of oligometastatic disease has become common as imaging techniques have advanced and the management of systemic disease has improved. Use of highly targeted, hypofractionated regimens of stereotactic body radiotherapy (SBRT) is ...

    Abstract Background: The treatment of oligometastatic disease has become common as imaging techniques have advanced and the management of systemic disease has improved. Use of highly targeted, hypofractionated regimens of stereotactic body radiotherapy (SBRT) is now a primary management option for patients with oligometastatic disease.
    Methods: The properties of SBRT are summarized and the results of retrospective and prospective studies of SBRT use in the management of oligometastases are reviewed. Future directions of SBRT, including optimizing dose and fractionation schedules, are also discussed.
    Results: SBRT can deliver highly conformal, dosed radiation treatments for ablative tumors in a few treatment sessions. Phase 1/2 trials and retrospective institutional results support use of SBRT as a treatment option for oligometastatic disease metastasized to the lung, liver, and spine, and SBRT offers adequate toxicity profiles with good rates of local control. Future directions will involve optimizing dose and fractionation schedules for select histologies to improve rates of local control while limiting toxicity to normal structures.
    Conclusions: SBRT offers an excellent management option for patients with oligometastases. However, additional research is still needed to optimize dose and fractionation schedules.
    MeSH term(s) Disease Management ; Dose Fractionation ; Humans ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Lung Neoplasms/secondary ; Lung Neoplasms/surgery ; Prospective Studies ; Radiation Tolerance ; Radiosurgery ; Retrospective Studies ; Spinal Neoplasms/secondary ; Spinal Neoplasms/surgery ; Treatment Outcome
    Language English
    Publishing date 2016-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1328503-8
    ISSN 1526-2359 ; 1073-2748
    ISSN (online) 1526-2359
    ISSN 1073-2748
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: A clinicogenomic model including GARD predicts outcome for radiation treated patients with HPV+ oropharyngeal squamous cell carcinoma.

    Ho, Emily / De Cecco, Loris / Cavalieri, Stefano / Sedor, Geoffrey / Hoebers, Frank / Brakenhoff, Ruud H / Scheckenbach, Kathrin / Poli, Tito / Yang, Kailin / Scarborough, Jessica A / Campbell, Shauna / Koyfman, Shlomo / Eschrich, Steven A / Caudell, Jimmy J / Kattan, Michael W / Licitra, Lisa / Torres-Roca, Javier F / Scott, Jacob G

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Background: Treatment decision-making in oropharyngeal squamous cell carcinoma (OPSCC) includes clinical stage, HPV status, and smoking history. Despite improvements in staging with separation of HPV-positive and -negative OPSCC in AJCC 8th edition ( ... ...

    Abstract Background: Treatment decision-making in oropharyngeal squamous cell carcinoma (OPSCC) includes clinical stage, HPV status, and smoking history. Despite improvements in staging with separation of HPV-positive and -negative OPSCC in AJCC 8th edition (AJCC8), patients are largely treated with a uniform approach, with recent efforts focused on de-intensification in low-risk patients. We have previously shown, in a pooled analysis, that the genomic adjusted radiation dose (GARD) is predictive of radiation treatment benefit and can be used to guide RT dose selection. We hypothesize that GARD can be used to predict overall survival (OS) in HPV-positive OPSCC patients treated with radiotherapy (RT).
    Methods: Gene expression profiles (Affymetrix Clariom D) were analyzed for 234 formalin-fixed paraffin-embedded samples from HPV-positive OPSCC patients within an international, multi-institutional, prospective/retrospective observational study including patients with AJCC 7th edition stage III-IVb. GARD, a measure of the treatment effect of RT, was calculated for each patient as previously described. In total, 191 patients received primary RT definitive treatment (chemoradiation or RT alone, and 43 patients received post-operative RT. Two RT dose fractionations were utilized for primary RT cases (70 Gy in 35 fractions or 69.96 Gy in 33 fractions). Median RT dose was 70 Gy (range 50.88-74) for primary RT definitive cases and 66 Gy (range 44-70) for post-operative RT cases. The median follow up was 46.2 months (95% CI, 33.5-63.1). Cox proportional hazards analyses were performed with GARD as both a continuous and dichotomous variable and time-dependent ROC analyses compared the performance of GARD with the NRG clinical nomogram for overall survival.
    Results: Despite uniform radiation dose utilization, GARD showed significant heterogeneity (range 30-110), reflecting the underlying genomic differences in the cohort. On multivariable analysis, each unit increase in GARD was associated with an improvement in OS (HR = 0.951 (0.911, 0.993), p = 0.023) compared to AJCC8 (HR = 1.999 (0.791, 5.047)), p = 0.143). ROC analysis for GARD at 36 months yielded an AUC of 80.6 (69.4, 91.9) compared with an AUC of 73.6 (55.4, 91.7) for the NRG clinical nomogram. GARD≥64.2 was associated with improved OS (HR = 0.280 (0.100, 0.781), p = 0.015). In a virtual trial, GARD predicts that uniform RT dose de-escalation results in overall inferior OS but proposes two separate genomic strategies where selective RT dose de-escalation in GARD-selected populations results in clinical equipoise.
    Conclusions: In this multi-institutional cohort of patients with HPV-positive OPSCC, GARD predicts OS as a continuous variable, outperforms the NRG nomogram and provides a novel genomic strategy to modern clinical trial design. We propose that GARD, which provides the first opportunity for genomic guided personalization of radiation dose, should be incorporated in the diagnostic workup of HPV-positive OPSCC patients.
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.14.23295538
    Database MEDical Literature Analysis and Retrieval System OnLINE

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