Personalized Radiotherapy in Cancer Care

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (15 October 2024) | Viewed by 8479

Special Issue Editors


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Guest Editor
Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
Interests: innovative radiation oncology technologies; stereotactic radiosurgery; gamma knife; stereotactic body radiation therapy; image-guided radiation therapy; combined immunotherapy and radiotherapy

E-Mail Website
Guest Editor
Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
Interests: brachytherapy; breast cancer; radiation oncology

Special Issue Information

Dear Colleagues,

In 2004, the 21-gene recurrence score (RS) was established as the first predictive gene test for patients with hormonal receptor positive and HER-2 negative breast cancer who would not benefit from chemotherapy. Since then, numerous predictive biomarkers have been discovered, which has allowed us to tailor treatments to patients to offer them the best chance of survival, while also minimizing treatment-related toxicity. While many of the new predictive biomarkers involve modified systemic therapy, to the focus is now on optimizing radiation treatments. Predictive genetic tests and the presence of biomarkers are being studied to optimize radiation doses and volumes. This Special Issue hopes to highlight the current status and future plans of personalized radiation therapy for patients with cancer at different disease sites.

Prof. Dr. Bin S. Teh
Dr. Waqar M. Haque
Guest Editors

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Keywords

  • predictive biomarkers
  • treatment-related toxicity
  • radiation treatments
  • radiation dose and volume
  • personalized radiation therapy

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Published Papers (8 papers)

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Research

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15 pages, 7455 KiB  
Article
Multiomics-Based Outcome Prediction in Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR)
by Haozhao Zhang, Michael Dohopolski, Strahinja Stojadinovic, Luiza Giuliani Schmitt, Soummitra Anand, Heejung Kim, Arnold Pompos, Andrew Godley, Steve Jiang, Tu Dan, Zabi Wardak, Robert Timmerman and Hao Peng
Cancers 2024, 16(19), 3425; https://doi.org/10.3390/cancers16193425 - 9 Oct 2024
Viewed by 632
Abstract
Objectives: This retrospective study aims to develop a multiomics approach that integrates radiomics, dosiomics, and delta features to predict treatment responses in brain metastasis (BM) patients undergoing PULSAR. Methods: A retrospective study encompassing 39 BM patients with 69 lesions treated with [...] Read more.
Objectives: This retrospective study aims to develop a multiomics approach that integrates radiomics, dosiomics, and delta features to predict treatment responses in brain metastasis (BM) patients undergoing PULSAR. Methods: A retrospective study encompassing 39 BM patients with 69 lesions treated with PULSAR was undertaken. Radiomics, dosiomics, and delta features were extracted from both pre-treatment and intra-treatment MRI scans alongside dose distributions. Six individual models, alongside an ensemble feature selection (EFS) model, were evaluated. The classification task focused on distinguishing between two lesion groups based on whether they exhibited a volume reduction of more than 20% at follow-up. Performance metrics, including sensitivity, specificity, accuracy, precision, F1 score, and the area under the receiver operating characteristic (ROC) curve (AUC), were assessed. Results: The EFS model integrated the features from pre-treatment radiomics, pre-treatment dosiomics, intra-treatment radiomics, and delta radiomics. It outperformed six individual models, achieving an AUC of 0.979, accuracy of 0.917, and F1 score of 0.821. Among the top nine features of the EFS model, six features came from post-wavelet transformation and three from original images. Conclusions: The study demonstrated the feasibility of employing a data-driven multiomics approach to predict treatment outcomes in BM patients receiving PULSAR treatment. Integrating multiomics with intra-treatment decision support in PULSAR shows promise for optimizing patient management and reducing the risks of under- or over-treatment. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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9 pages, 401 KiB  
Article
Localized Radiotherapy for Classic Kaposi’s Sarcoma: An Analysis of Lesion Characteristics and Treatment Response
by Junhee Park and Jeong Eun Lee
Cancers 2024, 16(18), 3194; https://doi.org/10.3390/cancers16183194 - 19 Sep 2024
Viewed by 480
Abstract
Objectives: Classic Kaposi’s sarcoma (CKS) is a rare malignancy with diverse clinical presentations, lacking a standard treatment. While localized therapies are commonly used for symptomatic lesions, radiotherapy (RT) has demonstrated effectiveness. This study aims to evaluate the efficacy of RT for treating skin [...] Read more.
Objectives: Classic Kaposi’s sarcoma (CKS) is a rare malignancy with diverse clinical presentations, lacking a standard treatment. While localized therapies are commonly used for symptomatic lesions, radiotherapy (RT) has demonstrated effectiveness. This study aims to evaluate the efficacy of RT for treating skin lesions in CKS. Methods: A retrospective analysis was conducted on patients with KS treated between April 2012 and January 2024. In total, 69 lesions in 16 patients were included. Treatment response was defined as follows: complete response (CR) indicated the absence of clinically detectable skin lesions and symptoms; partial response (PR) was a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was the appearance of new lesions within a previously irradiated field. Logistic regression analysis was used to investigate factors influencing response and in-field recurrence. Results: The median follow-up period was 52 months (range, 3–138 months). The overall response rate was 100%, with 92.8% of the patients achieving CR and 7.2% receiving PR. PR was observed in three patients with five lesions, all of which remained stable. In-field recurrence occurred in two patients with initially advanced disease, and all recurrent lesions responded to RT. No variables were significantly associated with response or in-field recurrence. Conclusions: RT for CKS showed a 100% response rate, with complete symptom relief in all cases. The effectiveness of RT was evident, even in cases involving disseminated lesions. Further research is needed to determine the optimal RT dose and fractionation. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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14 pages, 18600 KiB  
Article
Validation of In Vitro Trained Transcriptomic Radiosensitivity Signatures in Clinical Cohorts
by John D. O’Connor, Ian M. Overton and Stephen J. McMahon
Cancers 2023, 15(13), 3504; https://doi.org/10.3390/cancers15133504 - 5 Jul 2023
Cited by 1 | Viewed by 1237
Abstract
Transcriptomic personalisation of radiation therapy has gained considerable interest in recent years. However, independent model testing on in vitro data has shown poor performance. In this work, we assess the reproducibility in clinical applications of radiosensitivity signatures. Agreement between radiosensitivity predictions from published [...] Read more.
Transcriptomic personalisation of radiation therapy has gained considerable interest in recent years. However, independent model testing on in vitro data has shown poor performance. In this work, we assess the reproducibility in clinical applications of radiosensitivity signatures. Agreement between radiosensitivity predictions from published signatures using different microarray normalization methods was assessed. Control signatures developed from resampled in vitro data were benchmarked in clinical cohorts. Survival analysis was performed using each gene in the clinical transcriptomic data, and gene set enrichment analysis was used to determine pathways related to model performance in predicting survival and recurrence. The normalisation approach impacted calculated radiosensitivity index (RSI) values. Indeed, the limits of agreement exceeded 20% with different normalisation approaches. No published signature significantly improved on the resampled controls for prediction of clinical outcomes. Functional annotation of gene models suggested that many overlapping biological processes are associated with cancer outcomes in RT treated and non-RT treated patients, including proliferation and immune responses. In summary, different normalisation methods should not be used interchangeably. The utility of published signatures remains unclear given the large proportion of genes relating to cancer outcome. Biological processes influencing outcome overlapped for patients treated with or without radiation suggest that existing signatures may lack specificity. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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Review

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18 pages, 477 KiB  
Review
Risk-Stratified Radiotherapy in Pediatric Cancer
by Rituraj Upadhyay and Arnold C. Paulino
Cancers 2024, 16(20), 3530; https://doi.org/10.3390/cancers16203530 - 18 Oct 2024
Viewed by 534
Abstract
While the cure rate of cancer in children has markedly improved in the last few decades, late effects continue to be a problem in survivors. Radiotherapy, which is a major component of treatment in many cancers, is one of the major agents responsible [...] Read more.
While the cure rate of cancer in children has markedly improved in the last few decades, late effects continue to be a problem in survivors. Radiotherapy, which is a major component of treatment in many cancers, is one of the major agents responsible for late toxicity. In the past decade, radiotherapy has been omitted in patients achieving excellent response to chemotherapy, such as in Hodgkin lymphoma and some Wilms tumors with lung metastases. Likewise, response to chemotherapy has been used to determine whether lower doses of radiation can be delivered in intracranial germinoma and pediatric nasopharyngeal carcinoma. Molecular subtyping in medulloblastoma is currently being employed, and in WNT-pathway M0 tumors, the reduction in radiotherapy dose to the craniospinal axis and tumor bed is currently being investigated. Finally, dose escalation was recently evaluated in patients with rhabdomyosarcoma > 5 cm who do not achieve a complete response to initial 9 weeks of chemotherapy as well as for unresectable Ewing sarcoma patients to improve local control. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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14 pages, 1749 KiB  
Review
Personalized Brachytherapy: Applications and Future Directions
by Piyush Pathak, Justin J. Thomas, Arjit Baghwala, Chengfeng Li, Bin S. Teh, Edward B. Butler and Andrew M. Farach
Cancers 2024, 16(19), 3424; https://doi.org/10.3390/cancers16193424 - 9 Oct 2024
Viewed by 1028
Abstract
Brachytherapy offers a highly conformal and adaptive approach to radiation therapy for various oncologic conditions. This review explores the rationale, applications, technological advances, and future directions of personalized brachytherapy. Integration of advanced imaging techniques, 3D-printed applicators, and artificial intelligence are rapidly enhancing brachytherapy [...] Read more.
Brachytherapy offers a highly conformal and adaptive approach to radiation therapy for various oncologic conditions. This review explores the rationale, applications, technological advances, and future directions of personalized brachytherapy. Integration of advanced imaging techniques, 3D-printed applicators, and artificial intelligence are rapidly enhancing brachytherapy delivery and efficiency, while genomic tests and molecular biomarkers are refining patient and dose selection. Emerging research on combining brachytherapy with immunotherapy offers unique synergistic potential, and technologies such as intensity-modulated and shielded brachytherapy applicators present novel opportunities to further optimize dose distributions. Despite these promising advances, the field faces challenges including a need to train more practitioners and develop new approaches to treating a broader range of malignancies. As personalized medicine evolves, brachytherapy’s ability to deliver highly targeted, individualized treatments positions it as a critical component in future cancer care. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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23 pages, 1736 KiB  
Review
The Potential for Targeting G2/M Cell Cycle Checkpoint Kinases in Enhancing the Efficacy of Radiotherapy
by Emma Melia and Jason L. Parsons
Cancers 2024, 16(17), 3016; https://doi.org/10.3390/cancers16173016 - 29 Aug 2024
Viewed by 690
Abstract
Radiotherapy is one of the main cancer treatments being used for ~50% of all cancer patients. Conventional radiotherapy typically utilises X-rays (photons); however, there is increasing use of particle beam therapy (PBT), such as protons and carbon ions. This is because PBT elicits [...] Read more.
Radiotherapy is one of the main cancer treatments being used for ~50% of all cancer patients. Conventional radiotherapy typically utilises X-rays (photons); however, there is increasing use of particle beam therapy (PBT), such as protons and carbon ions. This is because PBT elicits significant benefits through more precise dose delivery to the cancer than X-rays, but also due to the increases in linear energy transfer (LET) that lead to more enhanced biological effectiveness. Despite the radiotherapy type, the introduction of DNA damage ultimately drives the therapeutic response through stimulating cancer cell death. To combat this, cells harbour cell cycle checkpoints that enables time for efficient DNA damage repair. Interestingly, cancer cells frequently have mutations in key genes such as TP53 and ATM that drive the G1/S checkpoint, whereas the G2/M checkpoint driven through ATR, Chk1 and Wee1 remains intact. Therefore, targeting the G2/M checkpoint through specific inhibitors is considered an important strategy for enhancing the efficacy of radiotherapy. In this review, we focus on inhibitors of Chk1 and Wee1 kinases and present the current biological evidence supporting their utility as radiosensitisers with different radiotherapy modalities, as well as clinical trials that have and are investigating their potential for cancer patient benefit. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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19 pages, 344 KiB  
Review
Embracing Personalized Strategies in Radiotherapy for Nasopharyngeal Carcinoma: Beyond the Conventional Bounds of Fields and Borders
by Pui Lam Yip, Rui You, Ming-Yuan Chen and Melvin L. K. Chua
Cancers 2024, 16(2), 383; https://doi.org/10.3390/cancers16020383 - 16 Jan 2024
Cited by 1 | Viewed by 2222
Abstract
Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TN-stages. Locoregional control rates have been impressive even from the 2D radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- [...] Read more.
Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TN-stages. Locoregional control rates have been impressive even from the 2D radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there has been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and the delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)

Other

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16 pages, 573 KiB  
Systematic Review
A Systematic Review of Phase II/III Trials of Hypofractionated versus Conventionally Fractionated Radiation Therapy in Stage III Non-Small Cell Lung Cancer Patients
by May N. Tsao, Yee Ung, Patrick Cheung, Ian Poon and Alexander V. Louie
Cancers 2024, 16(19), 3384; https://doi.org/10.3390/cancers16193384 - 3 Oct 2024
Viewed by 590
Abstract
Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic [...] Read more.
Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months–42.5 months) and toxicities such as grade 3 or higher esophagitis (0–42%) and grade 3 or higher pneumonitis (0–18%) were reported. Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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