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Biomedicines
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Advances in Immunotherapy and Radiation Therapy for Cancer
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Advances in Immunotherapy and Radiation Therapy for Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 13703

Special Issue Editors

Dr. Ivaylo B. Mihaylov

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Guest Editor
Department of Radiation Oncology, Miller School of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
Interests: radiotherapy; radiation therapy; cancer detection; radiation oncology
Dr. Benjamin Spieler

E-Mail Website
Guest Editor
Department of Radiation Oncology, Leonard M. Miller School of Medicine, University of Miami, 1475 NW 12th Ave., Suite 1500, Miami, FL 33136, USA
Interests: radiotherapy; radiation therapy; radiation oncology

Special Issue Information

Dear Colleagues,

The goal of this Special Issue is to publish innovative research related to immunotherapy combined with radiotherapy for cancer treatment. The inclusion of additional treatment modalities, such as chemotherapy, targeted therapy, hyperthermia, etc., is also of interest. The Special Issue is open to both clinical and preclinical studies, and to different disease sites and cancer types. The clinical studies should also encompass a preclinical component in order to be considered. The clinical component of interest is the impact of therapeutics on meaningful endpoints such as progression-free and overall survival. In the preclinical setting, improving the synergy of combination therapeutics through the optimization of sequencing, dosing, timing, and fractionation is of particular interest. Both mechanistic and phenomenological studies will be considered. Submissions may be related either to tumor control/response or to normal tissue side effects resulting from treatment. Predictive modeling intended to support clinical decision-making and pertinent to disease response or normal tissue complications is an additional area of interest.

Dr. Ivaylo B. Mihaylov
Dr. Benjamin Spieler
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • radiotherapy
  • immunotherapy
  • outcome
  • toxicity
  • normal tissue
  • abscopal
  • tumor
  • systemic
  • local
  • response

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Published Papers (7 papers)

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Research

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11 pages, 4145 KiB  
Article
The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study
by Georgios Evangelou, Ioannis P. Trontzas, Ioannis Gkiozos, Ioannis Vamvakaris, Christina Paraskeva, Maria Grammoustianou, Georgia Gomatou, Ioannis Tsamis, Ioannis Vathiotis, Maximillian Anagnostakis, Vasiliki Koliaraki and Kostas Syrigos
Biomedicines 2024, 12(6), 1161; https://doi.org/10.3390/biomedicines12061161 - 23 May 2024
Cited by 1 | Viewed by 1390
Abstract
Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with [...] Read more.
Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results: Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6–100%) and 14.3% (95% CI: 2.33–87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively). Conclusions: This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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12 pages, 1244 KiB  
Article
Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma—Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation
by Gregor Duwe, Lukas Müller, Christian Ruckes, Nikita Dhruva Fischer, Lisa Johanna Frey, Jan Hendrik Börner, Niklas Rölz, Maximilian Haack, Peter Sparwasser, Tobias Jorg, Christopher C. M. Neumann, Igor Tsaur, Thomas Höfner, Axel Haferkamp, Felix Hahn, Rene Mager and Maximilian Peter Brandt
Biomedicines 2023, 11(9), 2482; https://doi.org/10.3390/biomedicines11092482 - 7 Sep 2023
Viewed by 1582
Abstract
Background: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described [...] Read more.
Background: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. Methods: All patients with aUC (05/2017–10/2021) and aRCC (01/2012–05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. Results: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. Conclusions: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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16 pages, 2804 KiB  
Article
ADCY7 mRNA Is a Novel Biomarker in HPV Infection and Cervical High-Grade Squamous Lesions or Higher
by Lihua Chen, Lixiang Huang, Binhua Dong, Yu Gu, Wei Cang, Chen Li, Pengming Sun and Yang Xiang
Biomedicines 2023, 11(3), 868; https://doi.org/10.3390/biomedicines11030868 - 13 Mar 2023
Cited by 1 | Viewed by 2251
Abstract
The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this [...] Read more.
The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan–Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281–22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156–10.518), (0.370–8.137), and (0.171–4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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12 pages, 1112 KiB  
Article
Impact of Bone Metastases on Patients with Renal Cell Carcinoma or Melanoma Treated with Combotherapy Ipilimumab Plus Nivolumab
by Félix Pham, Samy Belkaid, Denis Maillet, Cyrille B. Confavreux, Stéphane Dalle and Julien Péron
Biomedicines 2022, 10(11), 2758; https://doi.org/10.3390/biomedicines10112758 - 31 Oct 2022
Cited by 6 | Viewed by 1701
Abstract
(1) Background: Ipilimumab plus nivolumab (combo-ICI) improves overall survival (OS) in patients with advanced renal cell carcinoma (RCC) or melanoma. The impact of bone metastases (BM) on survival outcomes of combo-ICI-treated patients is unknown. (2) Methods: This single-center retrospective observational study involved 36 [...] Read more.
(1) Background: Ipilimumab plus nivolumab (combo-ICI) improves overall survival (OS) in patients with advanced renal cell carcinoma (RCC) or melanoma. The impact of bone metastases (BM) on survival outcomes of combo-ICI-treated patients is unknown. (2) Methods: This single-center retrospective observational study involved 36 combo-ICI-treated patients with advanced RCC and 35 with melanoma. Clinical and laboratory data preceding the initiation of combo-ICI were collected. Univariate and multivariate Cox proportional hazard models were used to assess the effect of BM on overall survival (OS) and progression-free survival (PFS). (3) Results: zNine RCC and 11 melanoma patients had baseline BM. In unadjusted analysis, baseline BM was associated with a poorer OS in the RCC cohort. Baseline BM did not have any impact on survival outcomes in melanoma patients. After adjustment on baseline performance status and on neutrophil-to-lymphocyte ratio (NLR), the impact of BM was no longer significant, but a NLR ≥ 3 was significantly associated with a poorer OS in the RCC cohort. (4) Conclusions: The presence of baseline BM seems to be associated with worse outcomes in RCC combo-ICI-treated patients, while its effect might not be independent from the inflammatory state (approximated by the NLR). BM seems to have no impact on the outcomes of melanoma combo-ICI-treated patients. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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16 pages, 1409 KiB  
Article
Efficacy and Safety of Combined Brain Stereotactic Radiotherapy and Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with Brain Metastases
by Judith Porte, Caroline Saint-Martin, Thomas Frederic-Moreau, Marie-Ange Massiani, Laurence Bozec, Kim Cao, Pierre Verrelle, Joelle Otz, Eric Jadaud, Mathieu Minsat, Adriana Langer, Nicolas Girard, Gilles Créhange and Arnaud Beddok
Biomedicines 2022, 10(9), 2249; https://doi.org/10.3390/biomedicines10092249 - 10 Sep 2022
Cited by 6 | Viewed by 1982
Abstract
Background: To analyze the outcomes of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with immunotherapy (IT) and stereotactic radiotherapy (SRT) and to study the impact of the sequence between the two modalities. Methods: The authors reviewed the records [...] Read more.
Background: To analyze the outcomes of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with immunotherapy (IT) and stereotactic radiotherapy (SRT) and to study the impact of the sequence between the two modalities. Methods: The authors reviewed the records of 51 patients with 84 BM from NSCLC treated at Institut Curie with IT and SRT. BM were categorized into three groups: ‘SRT before IT’, ‘concurrent SRT and IT’, and ‘SRT after IT.’ Regional progression-free interval (R-PFI) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: After a median follow-up from SRT of 22.5 months (2.7–47.3), the 1-year and 2-year OS were 69.7% (95%CI [58.0–83.8]) and 44.0% [30.6–63.2], respectively. Concerning distant intracranial control, the 1-year and 2-year R-PFI were 40.1% [30.1–53.3] and 35.2% [25.1–49.4], respectively. Moreover, one-year R-PFI in ‘SRT before IT’, ‘concurrent SRT and IT’, and ‘SRT after IT’ groups were 24.1%, 49.6%, and 34.2%, respectively (p = 0.094). The type of therapeutic sequence did not appear to impact the risk of brain necrosis. Conclusions: The concurrent administration of SRT and IT appeared to offer the best locoregional control, without increasing the risk of toxicity, compared to patients treated with SRT before or after IT. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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Review

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29 pages, 4916 KiB  
Review
Emerging Ocular Side Effects of Immune Checkpoint Inhibitors: A Comprehensive Review
by Kevin Y. Wu, Yoel Yakobi, Diana D. Gueorguieva and Éric Mazerolle
Biomedicines 2024, 12(11), 2547; https://doi.org/10.3390/biomedicines12112547 - 7 Nov 2024
Viewed by 574
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering significant improvements in patient survival across various malignancies. However, their use is associated with a broad spectrum of immune-related adverse events (irAEs), including those affecting the eye and its surrounding structures, collectively termed ocular [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering significant improvements in patient survival across various malignancies. However, their use is associated with a broad spectrum of immune-related adverse events (irAEs), including those affecting the eye and its surrounding structures, collectively termed ocular irAEs (OirAEs). Although rare, OirAEs (e.g., keratitis, uveitis, retinal vasculitis, etc.) can significantly impact a patient’s quality of life, leading to ocular complications if left untreated. This review provides a comprehensive overview of OirAEs associated with ICIs, including their clinical manifestations, underlying mechanisms, and current management strategies. We delve into the anterior and posterior segment adverse events, highlighting conditions such as dry eye, uveitis, and retinal disorders, as well as neuro-ophthalmic and orbital complications. Furthermore, we discuss the challenges in diagnosing and treating these conditions, particularly given the overlap with other autoimmune and paraneoplastic syndromes. Finally, we identify key knowledge gaps and suggest future research directions aimed at optimizing the management of OirAEs while maintaining the efficacy of cancer therapy. This review underscores the need for increased awareness among clinicians to prevent irreversible ocular damage and enhance patient outcomes. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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15 pages, 1059 KiB  
Review
How to Manage a Patient with Ocular Metastases?
by Juliette Thariat, Laurys Boudin, Olivier Loria, Anh-Minh Nguyen, Laurent Kodjikian and Thibaud Mathis
Biomedicines 2022, 10(12), 3044; https://doi.org/10.3390/biomedicines10123044 - 25 Nov 2022
Cited by 7 | Viewed by 2515
Abstract
Ocular metastases are the most frequent ocular malignant tumors; their prevalence is estimated around 5–10% and is even higher in patients with breast or lung cancer. They represent various clinical situations, but they share the same hierarchical multidisciplinary therapeutic challenge with respect to [...] Read more.
Ocular metastases are the most frequent ocular malignant tumors; their prevalence is estimated around 5–10% and is even higher in patients with breast or lung cancer. They represent various clinical situations, but they share the same hierarchical multidisciplinary therapeutic challenge with respect to the way systemic and local therapies should be selected in combination or sequentially in the personalized medical history of a patient. The challenges include tumor control, eye preservation, and the minimization of iatrogenic damage to sensitive tissues surrounding the tumor in order to preserve vision. These aims should further contribute to maintaining quality of life in patients with metastases. Many patients with choroidal metastases have systemic molecular treatment for their primary tumor. However, secondary resistance to systemic treatment is common and may ultimately be associated with cancer relapse, even after an initial response. Therefore, it makes sense to propose local treatment concomitantly or after systemic therapy to provide a more sustainable response. The aim of this review is to present current therapeutic strategies in ocular metastases and discuss how to tailor the treatment to a specific patient. Full article
(This article belongs to the Special Issue Advances in Immunotherapy and Radiation Therapy for Cancer)
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