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Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

ABSTRACT: Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.

SUBMITTER: Ho AY

PROVIDER: S-EPMC7646202 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Ho Alice Y AY Wright Jean L JL Blitzblau Rachel C RC Mutter Robert W RW Duda Dan G DG Norton Larry L Bardia Aditya A Spring Laura L Isakoff Steven J SJ Chen Jonathan H JH Grassberger Clemens C Bellon Jennifer R JR Beriwal Sushil S Khan Atif J AJ Speers Corey C Dunn Samantha A SA Thompson Alastair A Santa-Maria Cesar A CA Krop Ian E IE Mittendorf Elizabeth E King Tari A TA Gupta Gaorav P GP

International journal of radiation oncology, biology, physics 20200514 1

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further ...[more]

PMID: 32417409

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Project description:PurposeIn a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa. We hypothesized that (1) radiation oncologists would find accurately delineating PCa tumors on conventional MRI challenging and (2) using RSIrs maps would improve radiation oncologists' accuracy for PCa tumor delineation.Methods and materialsIn this multi-institutional, international, prospective study, 44 radiation oncologists (participants) and 2 expert radiologists (experts) contoured prostate tumors on 39 total patient cases using conventional MRI with or without RSIrs maps. Participant volumes were compared to the consensus expert volumes. Contouring accuracy metrics included percent overlap with expert volume, Dice coefficient, conformal number, and maximum distance beyond expert volume.Results1604 participant volumes were produced. 40 of 44 participants (91%) completely missed ≥1 expert-defined target lesion without RSIrs, compared to 13 of 44 (30%) with RSIrs maps. On conventional MRI alone, 134 of 762 contour attempts (18%) completely missed the target, compared to 18 of 842 (2%) with RSIrs maps. Use of RSIrs maps improved all contour accuracy metrics by approximately 50% or more. Mixed effects modeling confirmed that RSIrs maps were the main variable driving improvement in all metrics. System Usability Scores indicated RSIrs maps significantly improved the contouring experience (72 vs. 58, p < 0.001).ConclusionsRadiation oncologists struggle with accurately delineating visible PCa tumors on conventional MRI. RSIrs maps improve radiation oncologists' ability to target MRI-visible tumors for prostate tumor boost.

Project description:PurposeIn March 2020, a 1-week ultrahypofractionated adjuvant breast radiation therapy schedule, 26 Gy in 5 fractions, and telehealth were adopted to reduce the risk of COVID-19 for staff and patients. This study describes real-world 1-year late toxicity for ultrahypofractionation (including a sequential boost) and patient perspectives on this new schedule and telehealth workflows.Methods and materialsConsecutive patients were enrolled between March and August 2020. Patient-reported outcome measures, including the presence of breast pain, swelling, firmness, and others, were recorded using the European Organisation for research and treatment of cancer quality of life questionairre (EORTC QLQ) BR45 at baseline, 3 months, 6 months, and 1 year. Virtual teleconferencing without video was used. Patients were invited to use video at 1 year for a physician-based assessment, including breast inspection. Patient-reported experience measures were also collected at 1 year to capture how a shortened schedule and telehealth influenced patient experience.ResultsIn total, 121 of 135 patients completed at least 2 assessments, of which 33 (25%) received a sequential boost. The majority of patients reported no toxicity or mild toxicity at all 3 time points: 76% at 3 months, 76% at 6 months, and 82% at 1 year. When comparing 26 Gy in 5 fractions alone versus 26 Gy in 5 fractions followed by a sequential boost, there was no difference in toxicity reported at 1 year. A total of 94% felt supported by the medical team throughout their treatment course using telehealth-only consultations. Only 27% actually agreed to video consultation for the purpose of breast inspection when offered.ConclusionsUltrahypofractionated breast radiation therapy leads to acceptable late toxicity at 1 year, even when followed by a hypofractionated tumor bed boost. Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high. Further investigation concerning the patient's acceptance of video consultations for a physician-based assessment, including breast inspection, is warranted.

Project description:BackgroundIn a recent phase III randomized control trial, delivering a focal radiotherapy (RT) boost to tumors visible on MRI was shown to improve disease-free survival and regional/distant metastasis-free survival for patients with prostate cancer-without increasing toxicity. The aim of this study was to assess how widely this technique is being applied in current practice, as well as physicians' perceived barriers toward its implementation.MethodsWe invited radiation oncologists to complete an online questionnaire assessing their use of intraprostatic focal boost in December 2022 and February 2023. To include perspectives from a broad range of practice settings, the invitation was distributed to radiation oncologists worldwide via email list, group text platform, and social media.Results263 radiation oncologist participants responded. The highest-represented countries were the United States (42%), Mexico (13%), and the United Kingdom (8%). The majority of participants worked at an academic medical center (52%) and considered their practice to be at least partially genitourinary (GU)-subspecialized (74%). Overall, 43% of participants reported routinely using intraprostatic focal boost. Complete GU-subspecialists were more likely to implement focal boost, with 61% reporting routine use. In both high-income and low-to-middle-income countries, less than half of participants routinely use focal boost. The most cited barriers were concerns about registration accuracy between MRI and CT (37%), concerns about risk of additional toxicity (35%), and challenges to accessing high-quality MRI (29%).ConclusionsTwo years following publication of a randomized trial of patient benefit without increased toxicity, almost half of the radiation oncologists surveyed are now routinely offering focal RT boost. Further adoption of this technique might be aided by increased access to high-quality MRI, better registration algorithms of MRI to CT simulation images, physician education on benefit-to-harm ratio, and training on contouring prostate lesions on MRI.

Dataset Information

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Publications

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Similar Datasets

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