Toxicity evaluation of ConvitVax breast cancer immunotherapy.
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ABSTRACT:
SUBMITTER: Duarte C MA
PROVIDER: S-EPMC8209199 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.
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Project description:Although unlikely to replace current standard of care therapies, immunotherapy is emerging as a critical component of breast cancer treatment. Despite initial setbacks, clinical benefit is now evident through immunomodulation and cancer vaccines. Over the past decade, passive immunotherapeutic strategies such as anti-HER2 monoclonal antibody (mAb) therapy have significantly improved the prognosis in HER2 overexpressing breast cancers. Novel active immunotherapeutic strategies include checkpoint blockade modifiers, also a mAb therapy. Although non-specific, checkpoint blockade modifiers show great promise in clinical trials. A form of active and specific immunotherapy, cancer vaccines may be used alone or in conjunction with these aforementioned mAb therapies. While there is significant initial promise, the complexities of the host immune system-tumor interaction and the vast array of potential immune targets require the field of cancer immunotherapy to be further developed. Here, we briefly discuss the field of breast immunotherapy to date and its implications for the future of breast cancer care.
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Project description:The idea of using the immune system to fight cancer is over 100 years old. A new molecular approach led to a better understanding of the immune system. Checkpoint regulation, understanding the roles of Tregs, Th1, and Th2, development of Chimeric antigen receptor (CAR)-T cells, as well as regulation of dendritic cells and macrophages, are just a few examples of our understating that has also led to the discovery of immune checkpoint inhibitors (ICIs) and modulators. This led the Nobel Prize committee in 2018, to award Dr. James P. Allison the Nobel Prize in medicine for the discovery of Cytotoxic T-lymphocyte-associated antigen-4, and Dr. Tasuku Honjo for the discovery of programmed cell death-1 (PD-1)/PD-1-ligand (PDL-1). Several ICIs are already approved by the regulatory authorities, and many more are currently used in studies of several solid tumors and hematologic malignancies. Positive studies have led to the US Food and Drug Administration (FDA) and European Medicines Agency approval of a number of these compounds, but none to date are approved in breast cancer (BC). Moreover, PD-1/PDL-1, MSI high (and dMMR), and tumor mutational burden are the currently "best" predictive markers for benefit from immunotherapy. BCs have some of these markers positive only in subsets but less frequently expressed than most other solid tumors, for example, malignant melanoma or non-small cell lung cancer. To improve the potential efficacy of ICI in BC, the addition of chemotherapy was one of the strategies. Many early and large clinical trials in all phases are underway in BC. We will discuss the role of immune system in BC editing, and the potential impact of immunotherapy in BC outcomes.
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Project description:PurposeTo investigate the use of advanced ultrasonic imaging to quantitatively evaluate normal-tissue toxicity in breast-cancer radiation treatment.Methods and materialsEighteen breast cancer patients who received radiation treatment were enrolled in an institutional review board-approved clinical study. Radiotherapy involved a radiation dose of 50.0 to 50.4 Gy delivered to the entire breast, followed by an electron boost of 10.0 to 16.0 Gy delivered to the tumor bed. Patients underwent scanning with ultrasound during follow-up, which ranged from 6 to 94 months (median, 22 months) postradiotherapy. Conventional ultrasound images and radio-frequency (RF) echo signals were acquired from treated and untreated breasts. Three ultrasound parameters, namely, skin thickness, Pearson coefficient, and spectral midband fit, were computed from RF signals to measure radiation-induced changes in dermis, hypodermis, and subcutaneous tissue, respectively. Ultrasound parameter values of the treated breast were compared with those of the untreated breast. Ultrasound findings were compared with clinical assessment using Radiation Therapy Oncology Group (RTOG) late-toxicity scores.ResultsSignificant changes were observed in ultrasonic parameter values of the treated vs. untreated breasts. Average skin thickness increased by 27.3%, from 2.05 ± 0.22 mm to 2.61 ± 0.52 mm; Pearson coefficient decreased by 31.7%, from 0.41 ± 0.07 to 0.28 ± 0.05; and midband fit increased by 94.6%, from -0.92 ± 7.35 dB to 0.87 ± 6.70 dB. Ultrasound evaluations were consistent with RTOG scores.ConclusionsQuantitative ultrasound provides a noninvasive, objective means of assessing radiation-induced changes to the skin and subcutaneous tissue. This imaging tool will become increasingly valuable as we continue to improve radiation therapy technique.
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