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Role of Radiation in the Treatment of Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 36598

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Dr. Arya Amini

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Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA
Interests: head and neck cancers; skin cancers; lung cancers; breast cancer; gastrointestinal cancers; stereotactic body radiation therapy; stereotactic radiosurgery
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Special Issue Information

Dear Colleagues,

For more than a century, radiation therapy (RT) has played an essential role in the treatment and cure of cancer patients. One of the most common roles of RT is in the adjuvant setting, defined typically as following surgical resection. From seminal work in breast cancer therapy decades ago, in which lumpectomy and RT were equivalent to mastectomy, to the prevention of local recurrences in critical areas, including the brain and head and neck, adjuvant radiation has been and remains an important component of cancer management. In the modern era, radiation oncology techniques have dramatically changed to a more targeted approach, utilizing intensity-modulated RT (IMRT) and image-guided RT (IGRT), which, in turn, allows for precise targeting of RT, minimizing the dose to critical structures. Additionally, heavy particles, including protons and carbon ions, are also being studied for their potential role in adjuvant RT, as their physical nature allows for a steeper dose fall-off. Further, in the era of more sophisticated targeted therapies, the role of adjuvant RT not only remains critical, especially as systemic therapies become better, but also is becoming somewhat more complex in regards to sequencing or potential combinations with new checkpoint inhibitors or molecularly targeted inhibitors. How RT interacts with these more novel agents is actively being assessed throughout the world. In this edition, we invite experts in radiation oncology to review the role of adjuvant radiation therapy based on specific tumor types. As always, what makes oncology an ever rapidly expanding and exciting field is its multidisciplinary nature. Adjuvant RT could not be done without a multidisciplinary discussion between radiation oncology, surgery, medical oncology, radiology, pathology, and supportive services.

Dr. Arya Amini
Guest Editor

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Keywords

radiation therapy (RT)
image-guided RT (IGRT)
intensity-modulated RT (IMRT)
Cancer
oncology

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Published Papers (9 papers)

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Research

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24 pages, 4280 KiB

Open AccessArticle

Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models

by Samar Al Bitar, Farah Ballout, Alissar Monzer, Mariam Kanso, Nour Saheb, Deborah Mukherji, Walid Faraj, Ayman Tawil, Samer Doughan, Maher Hussein, Wassim Abou-Kheir and Hala Gali-Muhtasib

Cancers 2022, 14(6), 1363; https://doi.org/10.3390/cancers14061363 - 8 Mar 2022

Cited by 15 | Viewed by 3795

Abstract

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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13 pages, 1677 KiB

Open AccessArticle

Reirradiation for Nasal Cavity or Paranasal Sinus Tumor—A Multi-Institutional Study

by Hideya Yamazaki, Gen Suzuki, Norihiro Aibe, Makoto Yasuda, Hiroya Shiomi, Ryoong-Jin Oh, Ken Yoshida, Satoaki Nakamura, Koji Konishi and Mikio Ogita

Cancers 2021, 13(24), 6315; https://doi.org/10.3390/cancers13246315 - 16 Dec 2021

Cited by 3 | Viewed by 2797

Abstract

We evaluated the efficacy and toxicity of reirradiation of nasal cavity or paranasal sinus tumors. We collected and analyzed multi-institutional data of reirradiation cases. Seventy-eight patients with nasal or paranasal sinus tumors underwent reirradiation. The median survival time was 20 months with a medial follow-up of 10.7 months. The 2-year local control and overall survival rates were 43% and 44%, respectively. Tumor volume (≤25 cm³), duration between previous radiotherapy and reirradiation (≤12 months), histology (squamous cell carcinoma), male sex, and lymph node involvement were predisposing factors for poor survival. Distant metastasis was observed in 20 patients (25.6%). Grade ≥ 3 adverse events were observed in 22% of the patients, including five grade 4 (8.6%) cases and one grade 5 (1.2%) case. Tumor location adjacent to the optic pathway was a significant predisposing factor for grade ≥3 visual toxicity. Reirradiation of nasal and paranasal sinus tumors is feasible and effective. However, adverse events, including disease-related toxicities, were significant. Prognostic factors emerge from this study to guide multidisciplinary approaches and clinical trial designs. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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12 pages, 385 KiB

Open AccessArticle

The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

by Michael Oertel, Jonas Martel, Jan-Henrik Mikesch, Sergiu Scobioala, Christian Reicherts, Kai Kröger, Georg Lenz, Matthias Stelljes and Hans Theodor Eich

Cancers 2021, 13(22), 5640; https://doi.org/10.3390/cancers13225640 - 11 Nov 2021

Cited by 10 | Viewed by 2301

Abstract

Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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11 pages, 962 KiB

Open AccessArticle

Adjuvant Radiotherapy Significantly Increases Neck Control and Survival in Early Oral Cancer Patients with Solitary Nodal Involvement: A National Cancer Registry Database Analysis

by Chia-Jen Tsai, Yu-Hsuan Kuo, Hung-Chang Wu, Chung-Han Ho, Yi-Chen Chen and Ching-Chieh Yang

Cancers 2021, 13(15), 3742; https://doi.org/10.3390/cancers13153742 - 26 Jul 2021

Cited by 9 | Viewed by 2214

Abstract

We assessed the role of adjuvant radiotherapy on neck control and survival in patients with early oral cancer with solitary nodal involvement. We identified pT1-2N1 oral cancer patients with or without adjuvant radiotherapy from the 2007–2015 Taiwan Cancer Registry database. The effect of adjuvant radiotherapy on 5-year neck control, overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan–Meier method, log-rank tests, and Cox regression analysis. Of 701 patients identified, 505 (72.0%) received adjuvant radiotherapy and 196 (28.0%) had surgery alone. Patients receiving adjuvant radiotherapy were more likely to be aged <65 years, pT2 stage, poorly graded and without comorbid conditions (all, p < 0.05). The 5-year OS and DFS differed significantly by receipt of adjuvant radiotherapy. Multivariable analysis showed adjuvant radiotherapy significantly associated with better 5-year OS (adjusted hazard ratio (aHR), 0.72; 95% confidence interval (CI), 0.54–0.97; p = 0.0288) and DFS (aHR, 0.64; 95% CI, 0.48–0.84; p = 0.0016). Stratified analysis indicated the greatest survival advantage for both 5-year OS and DFS in those with pT2 classification (p = 0.0097; 0.0009), and non-tongue disease (p = 0.0195; 0.0158). Moreover, adjuvant radiotherapy significantly protected against neck recurrence (aHR, 0.30; 95% CI, 0.18–0.51; p < 0.0001). Thus, adjuvant radiotherapy is associated with improved neck control and survival in these early oral cancer patients. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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12 pages, 442 KiB

Open AccessArticle

Pulmonary Toxicity after Total Body Irradiation—An Underrated Complication? Estimation of Risk via Normal Tissue Complication Probability Calculations and Correlation with Clinical Data

by Michael Oertel, Christopher Kittel, Jonas Martel, Jan-Henrik Mikesch, Marco Glashoerster, Matthias Stelljes and Hans Theodor Eich

Cancers 2021, 13(12), 2946; https://doi.org/10.3390/cancers13122946 - 12 Jun 2021

Cited by 16 | Viewed by 2411

Abstract

Total body irradiation (TBI) is an essential part of various conditioning regimens prior to allogeneic stem cell transplantation, but is accompanied by relevant (long-term) toxicities. In the lungs, a complex mechanism induces initial inflammation (pneumonitis) followed by chronic fibrosis. The hereby presented analysis investigates the occurrence of pulmonary toxicity in a large patient collective and correlates it with data derived from normal tissue complication probability (NTCP) calculations. The clinical data of 335 hemato-oncological patients undergoing TBI were analyzed with a follow-up of 85 months. Overall, 24.8% of all patients displayed lung toxicities, predominantly pneumonia and pulmonary obstructions (13.4% and 6.0%, respectively). NTCP calculations estimated median risks to be 20.3%, 0.6% and 20.4% for overall pneumonitis (both radiological and clinical), symptomatic pneumonitis and lung fibrosis, respectively. These numbers are consistent with real-world data from the literature and further specify radiological and clinical apparent toxicity rates. Overall, the estimated risk for clinical apparent pneumonitis is very low, corresponding to the probability of non-infectious acute respiratory distress syndrome, although the underlying pathophysiology is not identical. Radiological pneumonitis and lung fibrosis are expected to be more common but require a more precise documentation by the transplantation team, radiologists and radiation oncologists. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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12 pages, 405 KiB

Open AccessArticle

Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

by Massimo E. Abate, Silvia Cammelli, Letizia Ronchi, Barbara Diletto, Lorenza Gandola, Anna Paioli, Alessandra Longhi, Emanuela Palmerini, Nadia Puma, Angela Tamburini, Maurizio Mascarin, Elisa Coassin, Arcangelo Prete, Sebastian D. Asaftei, Carla Manzitti, Gianni Bisogno, Marta Pierobon, Luca Coccoli, Mariella Capasso, Giovanni Grignani, Giuseppe M. Milano, Valentina Kiren, Franca Fagioli, Stefano Ferrari, Piero Picci, Elisa Carretta and Roberto Luksch Show full author list Hide full author list

Cancers 2021, 13(11), 2789; https://doi.org/10.3390/cancers13112789 - 3 Jun 2021

Cited by 2 | Viewed by 3420

Abstract

Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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12 pages, 1075 KiB

Open AccessArticle

Multi-Institutional Retrospective Analysis of Carbon-Ion Radiotherapy for Patients with Locally Advanced Adenocarcinoma of the Uterine Cervix

by Noriyuki Okonogi, Ken Ando, Kazutoshi Murata, Masaru Wakatsuki, Shin-ei Noda, Daisuke Irie, Hiroshi Tsuji, Makio Shozu and Tatsuya Ohno

Cancers 2021, 13(11), 2713; https://doi.org/10.3390/cancers13112713 - 31 May 2021

Cited by 12 | Viewed by 3126

Abstract

The clinical significance of carbon-ion radiotherapy (CIRT) for adenocarcinoma (AC) of the uterine cervix has been assessed in several single-institutional studies. To validate the significance, we conducted a multi-institutional survey of CIRT for locally advanced AC (LAAC) of the uterine cervix. We retrospectively analyzed the clinical outcomes of patients with stage IIB–IVA LAAC of the uterine cervix who underwent chemo-CIRT or CIRT alone between April 2010 and April 2016. Patients received 74.4 Gy (relative biological effectiveness [RBE]) in 20 fractions of CIRT or 55.2 Gy (RBE) in 16 fractions of CIRT plus three sessions of brachytherapy. Patients aged ≤ 70 years with adequate bone marrow and organ function were administered cisplatin weekly (40 mg/m² per week for up to 5 weeks). Fifty-five patients were enrolled in this study. The median follow-up period was 67.5 months. The 5-year overall survival (OS) and local control (LC) rates were 68.6% and 65.2%, respectively. Multivariate analysis showed that the initial tumor response within 6 months was significantly associated with LC and OS. The present study represents promising outcomes of CIRT or chemo-CIRT for LAAC of the uterine cervix, especially in the cases showing initial rapid regression of the tumor. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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Review

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15 pages, 402 KiB

Open AccessReview

Role of Adjuvant Radiotherapy in Non-Small Cell Lung Cancer—A Review

by Krisztian Süveg, Ludwig Plasswilm, Thomas Iseli, Pawel Leskow, Galina Farina Fischer and Paul Martin Putora

Cancers 2022, 14(7), 1617; https://doi.org/10.3390/cancers14071617 - 23 Mar 2022

Cited by 8 | Viewed by 3649

Abstract

Background: For patients with completely resected non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (pN2), the administration of adjuvant chemotherapy is the standard of care. The role of postoperative radiation therapy (PORT) is controversial. Methods: We describe the current literature focusing on the role of PORT in completely resected NSCLC patients with pN2 involvement and reflect on its role in current guidelines. Results: Based on the results of the recent Lung ART and PORT-C trials, the authors conclude that PORT cannot be generally recommended for all resected pN2 NSCLC patients. A substantial decrease in the locoregional relapse rate without translating into a survival benefit suggests that some patients with risk factors might benefit from PORT. This must be balanced against the risk of cardiopulmonary toxicity with potentially associated mortality. Lung ART has already changed the decision making for the use of PORT in daily practice for many European lung cancer experts, with lower rates of recommendations for PORT overall. Conclusions: PORT is still used, albeit decreasingly, for completely resected NSCLC with pN2 involvement. High-level evidence for its routine use is lacking. Further analyses are required to identify patients who would potentially benefit from PORT. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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12 pages, 755 KiB

Open AccessReview

An Updated Review on Head and Neck Cancer Treatment with Radiation Therapy

by Garrett Anderson, Maryam Ebadi, Kim Vo, Jennifer Novak, Ameish Govindarajan and Arya Amini

Cancers 2021, 13(19), 4912; https://doi.org/10.3390/cancers13194912 - 30 Sep 2021

Cited by 100 | Viewed by 11757

Abstract

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed. Full article

(This article belongs to the Special Issue Role of Radiation in the Treatment of Cancer)

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