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10 pages, 359 KiB

Open AccessArticle

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre

by Caroline Gee, Catherine Fleuret, Ana Wilson, Daniel Levine, Ramy Elhusseiny, Ann Muls, David Cunningham and Darina Kohoutova

Cancers 2021, 13(24), 6213; https://doi.org/10.3390/cancers13246213 - 10 Dec 2021

Cited by 6 | Viewed by 3747

Abstract

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019–January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine [...] Read more.

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019–January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 females, 66%) were diagnosed with BAM. Mean age was 59 +/− 12 years. The largest group were females with gynaecological cancer (35), followed by haematology group (15), colorectal/anal (13), prostate (9), upper gastrointestinal cancer (6), another previous malignancy (9). Severe BAM was most common in haematology (10/15; 67%) and gynaecological group (21/35; 60%). Medication and low-fat diet were commenced in 65/87 (75%), medication in 10/87 (11%), diet in 6/87 (7%). Colesevelam was used in 71/75 (95%). Symptoms improved in 74/87 (85%) patients. Vitamin D insufficiency/deficiency was diagnosed in 62/87 (71%), vitamin B12 deficiency in 39/87 (45%). BAM is a common condition in this cohort however treatments are highly effective. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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12 pages, 1123 KiB

Open AccessArticle

The Impact of Post-Mastectomy Radiotherapy on Survival Outcomes in Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy

by Janghee Lee, Jee-Ye Kim, Soong-June Bae, Yeona Cho, Jung-Hwan Ji, Dooreh Kim, Sung-Gwe Ahn, Hyung-Seok Park, Seho Park, Seung-Il Kim, Byeong-Woo Park and Joon Jeong

Cancers 2021, 13(24), 6205; https://doi.org/10.3390/cancers13246205 - 9 Dec 2021

Cited by 5 | Viewed by 2534

Abstract

This study aimed to determine whether post-mastectomy radiotherapy (PMRT) is beneficial for the prognosis of patients who achieved pathologic complete response (pCR), or who had minimal residual disease, after undergoing neoadjuvant chemotherapy (NAC). Patients who underwent a total mastectomy between 2006 and 2018, [...] Read more.

This study aimed to determine whether post-mastectomy radiotherapy (PMRT) is beneficial for the prognosis of patients who achieved pathologic complete response (pCR), or who had minimal residual disease, after undergoing neoadjuvant chemotherapy (NAC). Patients who underwent a total mastectomy between 2006 and 2018, after NAC, were included. Patients who did not receive PMRT were matched using 1:3 propensity score matching (PSM). Kaplan–Meier survival curves were used to compare locoregional recurrence-free survival (LRRFS) and overall survival (OS). A total of 368 patients were included after 1:3 PSM. PMRT improved the LRRFS (p = 0.016) and OS (p = 0.017) rates of patients who underwent NAC. However, PMRT did not affect the prognosis of patients with pCR (LRRFS: p = 0.999; OS: p = 0.453). In addition, PMRT had a limited effect on LRRFS and OS in patients who responded well to NAC, with a neoadjuvant response index (NRI) value of 0.7–1.0 (LRRFS: p = 0.568; OS: p = 0.875). PMRT improved the OS of patients with a large residual tumor burden, such as nodal metastases or pathologic stage II/III. The benefits of PMRT vary depending on the patients’ response to NAC, although PMRT is useful for treating patients who underwent NAC. PMRT can be omitted, not only in patients with pCR, but also in good responders with an NRI value of 0.7–1.0. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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14 pages, 1053 KiB

Open AccessArticle

Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617

by Jian-Yue Jin, Chen Hu, Ying Xiao, Hong Zhang, Rebecca Paulus, Susannah G. Ellsworth, Steven E. Schild, Jeffrey A. Bogart, Michael Chris Dobelbower, Vivek S. Kavadi, Samir Narayan, Puneeth Iyengar, Cliff Robinson, Joel S. Greenberger, Christopher Koprowski, Mitchell Machtay, Walter Curran, Hak Choy, Jeffrey D. Bradley and Feng-Ming (Spring) Kong

Cancers 2021, 13(24), 6193; https://doi.org/10.3390/cancers13246193 - 8 Dec 2021

Cited by 56 | Viewed by 4692

Abstract

Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a [...] Read more.

Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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16 pages, 2027 KiB

Open AccessArticle

Molecular Response to Combined Molecular- and External Radiotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC)

by Treewut Rassamegevanon, Louis Feindt, Lydia Koi, Johannes Müller, Robert Freudenberg, Steffen Löck, Wiebke Sihver, Enes Çevik, Ariane Christel Kühn, Cläre von Neubeck, Annett Linge, Hans-Jürgen Pietzsch, Jörg Kotzerke, Michael Baumann, Mechthild Krause and Antje Dietrich

Cancers 2021, 13(22), 5595; https://doi.org/10.3390/cancers13225595 - 9 Nov 2021

Cited by 5 | Viewed by 2573

Abstract

Combination treatment of molecular targeted and external radiotherapy is a promising strategy and was shown to improve local tumor control in a HNSCC xenograft model. To enhance the therapeutic value of this approach, this study investigated the underlying molecular response. Subcutaneous HNSCC FaDu [...] Read more.

Combination treatment of molecular targeted and external radiotherapy is a promising strategy and was shown to improve local tumor control in a HNSCC xenograft model. To enhance the therapeutic value of this approach, this study investigated the underlying molecular response. Subcutaneous HNSCC FaDu_DD xenografts were treated with single or combination therapy (X-ray: 0, 2, 4 Gy; anti-EGFR antibody (Cetuximab) (un-)labeled with Yttrium-90 (⁹⁰Y)). Tumors were excised 24 h post respective treatment. Residual DNA double strand breaks (DSB), mRNA expression of DNA damage response related genes, immunoblotting, tumor histology, and immunohistological staining were analyzed. An increase in number and complexity of residual DNA DSB was observed in FaDu_DD tumors exposed to the combination treatment of external irradiation and ⁹⁰Y-Cetuximab relative to controls. The increase was observed in a low oxygenated area, suggesting the expansion of DNA DSB damages. Upregulation of genes encoding p21^cip1/waf1 (CDKN1A) and GADD45α (GADD45A) was determined in the combination treatment group, and immunoblotting as well as immunohistochemistry confirmed the upregulation of p21^cip1/waf1. The increase in residual γH2AX foci leads to the blockage of cell cycle transition and subsequently to cell death, which could be observed in the upregulation of p21^cip1/waf1 expression and an elevated number of cleaved caspase-3 positive cells. Overall, a complex interplay between DNA damage repair and programmed cell death accounts for the potential benefit of the combination therapy using ⁹⁰Y-Cetuximab and external radiotherapy. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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12 pages, 1406 KiB

Open AccessArticle

Modern Rotational Radiation Techniques with Volumetric Modulated Arc Therapy or Helical Tomotherapy for Optimal Sparing of the Lung and Heart in Left-Breast Cancer Radiotherapy Plus Regional Nodal Irradiation: A Comparative Dosimetric Analysis

by Pei-Yu Hou, Chen-Hsi Hsieh, Le-Jung Wu, Chen-Xiong Hsu, Deng-Yu Kuo, Yueh-Feng Lu, Hui-Ju Tien, Hsiu-Wen Hsiao, Pei-Wei Shueng and Shih-Ming Hsu

Cancers 2021, 13(20), 5043; https://doi.org/10.3390/cancers13205043 - 9 Oct 2021

Cited by 6 | Viewed by 2554

Abstract

Background: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects [...] Read more.

Background: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects patient outcomes. Modern arc RT techniques can improve normal organ sparing compared with conventional techniques. The aim of this study was to explore the optimal technique for left-breast RT with RNI. Methods: We retrospectively reviewed patients receiving RT with RNI for left-breast cancer. We used modern arc RT techniques with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT) with a novel block technique, and compared differences in dosimetry parameters between the two groups. Subgroup analysis of RNI with or without internal mammary node (IMN) volume was also performed. Results: A total of 108 eligible patients were enrolled between 2017 and 2020, of whom 70 received VMAT and 38 received HT. The median RT dose was 55 Gy. No significant differences were found regarding the surgery, RT dose, number of fractions, target volume, and RNI volume between the VMAT and HT groups. VMAT reduced the heart mean dose more than HT (3.82 vs. 5.13 Gy, p < 0.001), as well as the cardiac parameters of V5–V20, whole-lung mean dose, lung parameters of V5–V20, and contralateral-breast and esophagus mean dose. In the subgroup analysis of RNI with IMNs, the advantage of VMAT persisted in protecting the heart, lung, contralateral breast, and esophagus. HT was beneficial for lowering the thyroid mean dose. For RNI without IMN, VMAT improved the low-dose exposure of the heart and lung, but HT was similar to VMAT in terms of heart, whole-lung, and contralateral-breast mean dose. Conclusions: For patients with left-breast cancer receiving adjuvant RT with RNI, VMAT reduced the exposure dose to the heart, lung, contralateral breast, and esophagus compared with HT. VMAT was superior to HT in terms of normal organ sparing in the patients who underwent RNI with IMN irradiation. Considering the reduction in normal organ exposure and potential toxicity, VMAT is the optimal technique for patients receiving RNI when deep inspiration breath-hold is not available. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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8 pages, 253 KiB

Open AccessArticle

Risk Factors for Radiation Necrosis in Patients Undergoing Cranial Stereotactic Radiosurgery

by Johannes Kerschbaumer, Matthias Demetz, Aleksandrs Krigers, Meinhard Nevinny-Stickel, Claudius Thomé and Christian F. Freyschlag

Cancers 2021, 13(19), 4736; https://doi.org/10.3390/cancers13194736 - 22 Sep 2021

Cited by 18 | Viewed by 2230

Abstract

Purpose: single-staged stereotactic radiosurgery (SRS) is an established part of the multimodal treatment in neuro-oncology. Radiation necrosis after high-dose irradiation is a known complication, but there is a lack of evidence about the risk factors. The aim of this study was to evaluate [...] Read more.

Purpose: single-staged stereotactic radiosurgery (SRS) is an established part of the multimodal treatment in neuro-oncology. Radiation necrosis after high-dose irradiation is a known complication, but there is a lack of evidence about the risk factors. The aim of this study was to evaluate possible risk factors for radiation necrosis in patients undergoing radiosurgery. Methods: patients treated with radiosurgery between January 2004 and November 2020 were retrospectively analyzed. The clinical data, imaging and medication were gathered from electronic patient records. The largest diameter of the tumors was measured using MRI scans in T1 weighted imaging with gadolinium and the edema in T2 weighted sequences. The diagnosis of a radiation necrosis was established analyzing imaging criteria combined with clinical course or pathologically confirmed by subsequent surgical intervention. Patients developing radiation necrosis detected after SRS were compared to patients without evidence of an overshooting irradiation reaction. Results: 388 patients were included retrospectively, 61 (15.7%) of whom developed a radiation necrosis. Median follow-up was 24 (6–62) months with a radiation necrosis after 8 (6–12) months. The most frequent tumors were metastases in 47.2% of the cases, followed by acoustic neuromas in 32.2% and meningiomas in 13.4%. Seventy-three (18.9%) patients already underwent one or more previous radiosurgical procedures for different lesions. The mean largest diameter of the tumors amounted to 16.3 mm (±6.1 mm). The median—80%—isodose administered was 16 (14–25) Gy. Of the radiation necroses, 25 (43.1%) required treatment, in 23 (39.7%) thereof, medical treatment was applied and in 2 (3.4%) cases, debulking surgery was performed. In this study, significantly more radiation necroses arose in patients with higher doses (HR 1.3 [CI 1.2; 1.5], p < 0.001) leading to a risk increment of over 180% between a radiation isodose of 14 and 20 Gy. The maximum diameter was a second significant risk factor (p = 0.028) with an HR of 1065 for every 1 mm increase in multivariate analysis. Conclusion: large diameter and high doses were reliable independent risk factors leading to more frequent radiation necroses, regardless of tumor type in patients undergoing radiosurgery. Alternative therapeutic procedures may be considered in lesions with large volume and an expected high radiation doses due to the increased risk of developing radiation necrosis. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

7 pages, 527 KiB

Open AccessArticle

Impact of Adjuvant Radiotherapy in Patients with Central Neurocytoma: A Multicentric International Analysis

by Laith Samhouri, Mohamed A. M. Meheissen, Ahmad K. H. Ibrahimi, Abdelatif Al-Mousa, Momen Zeineddin, Yasser Elkerm, Zeyad M. A. Hassanein, Abdelsalam Attia Ismail, Hazem Elmansy, Motasem M. Al-Hanaqta, Omar A. AL-Azzam, Amr Abdelaziz Elsaid, Christopher Kittel, Oliver Micke, Walter Stummer, Khaled Elsayad and Hans Theodor Eich

Cancers 2021, 13(17), 4308; https://doi.org/10.3390/cancers13174308 - 26 Aug 2021

Cited by 10 | Viewed by 2864

Abstract

Background: Central neurocytoma (CN) is a rare tumor accounting for <0.5% of all intracranial tumors. Surgery ± radiotherapy is the mainstay treatment. This international multicentric study aims to evaluate the outcomes of CNs patients after multimodal therapies and identify predictive factors. Patients and [...] Read more.

Background: Central neurocytoma (CN) is a rare tumor accounting for <0.5% of all intracranial tumors. Surgery ± radiotherapy is the mainstay treatment. This international multicentric study aims to evaluate the outcomes of CNs patients after multimodal therapies and identify predictive factors. Patients and methods: We retrospectively identified 33 patients with CN treated between 2005 and 2019. Treatment characteristics and outcomes were assessed. Results: All patients with CN underwent surgical resection. Radiotherapy was delivered in 19 patients. The median radiation dose was 54 Gy (range, 50–60 Gy). The median follow-up time was 56 months. The 5-year OS and 5-year PFS were 90% and 76%, respectively. Patients who received radiotherapy had a significantly longer PFS than patients without RT (p = 0.004) and a trend towards longer OS. In addition, complete response after treatments was associated with longer PFS (p = 0.07). Conclusions: Using RT seems to be associated with longer survival rates with an acceptable toxicity profile. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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15 pages, 534 KiB

Open AccessFeature PaperArticle

Improved Survival after Breast-Conserving Therapy Compared with Mastectomy in Stage I-IIA Breast Cancer

by Ivica Ratosa, Gaber Plavc, Nina Pislar, Tina Zagar, Andraz Perhavec and Pierfrancesco Franco

Cancers 2021, 13(16), 4044; https://doi.org/10.3390/cancers13164044 - 11 Aug 2021

Cited by 8 | Viewed by 3471

Abstract

In the current study, we sought to compare survival outcomes after breast-conserving therapy (BCT) or mastectomy alone in patients with stage I-IIA breast cancer, whose tumors are typically suitable for both locoregional treatments. The study cohort consisted of 1360 patients with stage I-IIA [...] Read more.

In the current study, we sought to compare survival outcomes after breast-conserving therapy (BCT) or mastectomy alone in patients with stage I-IIA breast cancer, whose tumors are typically suitable for both locoregional treatments. The study cohort consisted of 1360 patients with stage I-IIA (T1–2N0 or T0–1N1) breast cancer diagnosed between 2001 and 2013 and treated with either BCT (n = 1021, 75.1%) or mastectomy alone (n = 339, 24.9%). Median follow-ups for disease-free survival (DFS) and overall survival (OS) were 6.9 years (range, 0.3–15.9) and 7.5 years (range, 0.2–25.9), respectively. Fifteen (1.1%), 14 (1.0%) and 48 (3.5%) patients experienced local, regional, and distant relapse, respectively. For the whole cohort of patients, the estimated 5-year DFS and OS were 96% and 97%, respectively. After stratification based on the type of local treatment, the estimated 5-year DFS for BCT was 97%, while it was 91% (p < 0.001) for mastectomy-only treatment. Inverse probability of treatment weighting matching based on confounding confirmed that mastectomy was associated with worse DFS (HR 2.839, 95% CI 1.760–4.579, p < 0.0001), but not with OS (HR 1.455, 95% CI 0.844–2.511, p = 0.177). In our study, BCT was shown to have improved disease-specific outcomes compared to mastectomy alone, emphasizing the important role of adjuvant treatments, including postoperative radiation therapy, in patients with early-stage breast cancer at diagnosis. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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21 pages, 4330 KiB

Open AccessArticle

Modelling Radiation-Induced Salivary Dysfunction during IMRT and Chemotherapy for Nasopharyngeal Cancer Patients

by Anna Cavallo, Nicola Alessandro Iacovelli, Nadia Facchinetti, Tiziana Rancati, Salvatore Alfieri, Tommaso Giandini, Alessandro Cicchetti, Carlo Fallai, Rossana Ingargiola, Lisa Licitra, Laura Locati, Stefano Cavalieri, Emanuele Pignoli, Domenico Attilio Romanello, Riccardo Valdagni and Ester Orlandi

Cancers 2021, 13(16), 3983; https://doi.org/10.3390/cancers13163983 - 6 Aug 2021

Cited by 3 | Viewed by 2320

Abstract

Background: Radiation-induced xerostomia is one of the most prevalent adverse effects of head and neck cancer treatment, and it could seriously affect patients’ qualities of life. It results primarily from damage to the salivary glands, but its onset and severity may also be [...] Read more.

Background: Radiation-induced xerostomia is one of the most prevalent adverse effects of head and neck cancer treatment, and it could seriously affect patients’ qualities of life. It results primarily from damage to the salivary glands, but its onset and severity may also be influenced by other patient-, tumour-, and treatment-related factors. We aimed to build and validate a predictive model for acute salivary dysfunction (aSD) for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors. Methods: A cohort of consecutive NPC patients treated curatively with IMRT and chemotherapy at 70 Gy (2–2.12 Gy/fraction) were utilised. Parotid glands (cPG, considered as a single organ) and the oral cavity (OC) were selected as organs-at-risk. The aSD was assessed at baseline and weekly during RT, grade ≥ 2 aSD chosen as the endpoint. Dose-volume histograms were reduced to the Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Model validation was performed on two cohorts of patients with prospective aSD, and scored using the same schedule/scale: a cohort (NPC_V) of NPC patients (as in model training), and a cohort of mixed non-NPC head and neck cancer patients (HNC_V). Results: The model training cohort included 132 patients. Grade ≥ 2 aSD was reported in 90 patients (68.2%). Analyses resulted in a 4-variables model, including doses of up to 98% of cPG (cPG_D98%, OR = 1.04), EUD to OC with n = 0.05 (OR = 1.11), age (OR = 1.08, 5-year interval) and smoking history (OR = 1.37, yes vs. no). Calibration was good. The NPC_V cohort included 38 patients, with aSD scored in 34 patients (89.5%); the HNC_V cohort included 93 patients, 77 with aSD (92.8%). As a general observation, the incidence of aSD was significantly different in the training and validation populations (p = 0.01), thus impairing calibration-in-the-large. At the same time, the effect size for the two dosimetric factors was confirmed. Discrimination was also satisfactory in both cohorts: AUC was 0.73, and 0.68 in NPC_V and HNC_V cohorts, respectively. Conclusion: cPG D98% and the high doses received by small OC volumes were found to have the most impact on grade ≥ 2 acute xerostomia, with age and smoking history acting as a dose-modifying factor. Findings on the development population were confirmed in two prospectively collected validation populations. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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13 pages, 505 KiB

Open AccessArticle

Intensity-Modulated Radiation Therapy with Simultaneous Integrated Boost for Clinically Node-Positive Prostate Cancer: A Single-Institutional Retrospective Study

by Masahiro Onishi, Hidemasa Kawamura, Kazutoshi Murata, Tatsuro Inoue, Hiroto Murata, Yosuke Takakusagi, Noriyuki Okonogi, Yu Ohkubo, Masahiko Okamoto, Takuya Kaminuma, Tetsuo Sekihara, Takashi Nakano and Tatsuya Ohno

Cancers 2021, 13(15), 3868; https://doi.org/10.3390/cancers13153868 - 31 Jul 2021

Cited by 3 | Viewed by 3395

Abstract

This study aimed to evaluate clinical outcomes and the toxicity of intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) combined with androgen-deprivation therapy for clinically node-positive (cN1) prostate cancer. We retrospectively analyzed 97 patients with cN1 prostate cancer who received SIB-IMRT between June [...] Read more.

This study aimed to evaluate clinical outcomes and the toxicity of intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) combined with androgen-deprivation therapy for clinically node-positive (cN1) prostate cancer. We retrospectively analyzed 97 patients with cN1 prostate cancer who received SIB-IMRT between June 2008 and October 2017 at our hospital. The prescribed dosages delivered to the prostate and seminal vesicle, elective node area, and residual lymph nodes were 69, 54, and 60 Gy in 30 fractions, respectively. Kaplan–Meier analysis was used to determine 5-year biochemical relapse-free survival (bRFS), relapse-free survival (RFS), overall survival (OS), and prostate cancer-specific survival (PCSS). Toxicity was evaluated using the Common Terminology Criteria for Adverse Events ver. 4.0. Over a median follow-up duration of 60 months, the 5-year bRFS, RFS, OS, and PCSS were 85.1%, 88.1%, 92.7% and 95.0%, respectively. Acute Grade 2 genito-urinary (GU) and gastro-intestinal (GI) toxicities were observed in 10.2% and 2.1%, respectively, with no grade ≥3 toxicities being detected. The cumulative incidence rates of 5-year Grade ≥2 late GU and GI toxicities were 4.7% and 7.4%, respectively, with no Grade 4 toxicities being detected. SIB-IMRT for cN1 prostate cancer demonstrated favorable 5-year outcomes with low incidences of toxicity. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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15 pages, 7614 KiB

Open AccessArticle

The DNA Damage Response Is Differentially Involved in HPV-Positive and HPV-Negative Radioresistant Head and Neck Squamous Cell Carcinoma

by Marieke Bamps, Rüveyda Dok and Sandra Nuyts

Cancers 2021, 13(15), 3717; https://doi.org/10.3390/cancers13153717 - 23 Jul 2021

Cited by 11 | Viewed by 2626

Abstract

Radioresistance is a major cause of recurrences and radiotherapy (RT) failure in head and neck squamous cell carcinoma (HNSCC). DNA damage response (DDR) is known to be important for RT response, but its role in radioresistance is not fully understood. Here, we assessed [...] Read more.

Radioresistance is a major cause of recurrences and radiotherapy (RT) failure in head and neck squamous cell carcinoma (HNSCC). DNA damage response (DDR) is known to be important for RT response, but its role in radioresistance is not fully understood. Here, we assessed the role of DDR in the radioresistance process of HNSCC by generating radioresistant clones from both HPV-positive SCC154 and HPV-negative SCC61 cells. We show that fractionated RT decreased RT response of HPV-positive and HPV-negative radioresistant clones in vitro and in vivo. Moreover, HPV-positive and HPV-negative radioresistant clones were characterized by differential DDR response. HPV-positive radioresistant clones showed less residual double-strand break damage and increased G2/M arrest recovery after RT, indicating an acquisition of increased DDR kinetics. In contrast, HPV-negative radioresistant clones showed less micronucleated cells after RT and increased survival upon checkpoint inhibition, indicating an increased replicative capacity. Inhibiting key factors of DDR in combination with RT rescued the radioresistant phenotype of both HPV-positive and HPV-negative radioresistant clones. Altogether, our results not only highlight the importance of DDR response in the radioresistance process of HPV-positive and HPV-negative HNSCC, but also provide possibilities for new therapies for HNSCC patients in recurrent settings. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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14 pages, 3550 KiB

Open AccessArticle

Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

by Minglei Kang, Shouyi Wei, J. Isabelle Choi, Charles B. Simone II and Haibo Lin

Cancers 2021, 13(14), 3549; https://doi.org/10.3390/cancers13143549 - 15 Jul 2021

Cited by 43 | Viewed by 4206

Abstract

To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for [...] Read more.

To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot < 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate; DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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15 pages, 3132 KiB

Open AccessArticle

Quality of Automated Stereotactic Radiosurgery Plans in Patients with 4 to 10 Brain Metastases

by Anna Petoukhova, Roland Snijder, Rudolf Wiggenraad, Linda de Boer-de Wit, Ivonne Mudde-van der Wouden, Mireille Florijn and Jaap Zindler

Cancers 2021, 13(14), 3458; https://doi.org/10.3390/cancers13143458 - 10 Jul 2021

Cited by 5 | Viewed by 3634

Abstract

The purpose was to compare linac-based stereotactic radiosurgery and hypofractionated radiotherapy plan quality of automated planning, intensity modulated radiotherapy (IMRT) and manual dynamic conformal arc (DCA) plans as well as single- and multiple-isocenter techniques for multiple brain metastases (BM). For twelve patients with [...] Read more.

The purpose was to compare linac-based stereotactic radiosurgery and hypofractionated radiotherapy plan quality of automated planning, intensity modulated radiotherapy (IMRT) and manual dynamic conformal arc (DCA) plans as well as single- and multiple-isocenter techniques for multiple brain metastases (BM). For twelve patients with four to ten BM, seven non-coplanar linac-based plans were created: a manually planned DCA plan with a separate isocenter for each metastasis, a single-isocenter dynamic IMRT plan, an automatically generated single-isocenter volumetric modulated arc radiotherapy (VMAT) plan, four automatically generated single-isocenter DCA plans with three or five couch angles, with high or low sparing of normal tissue. Paddick conformity index, gradient index (GI), mean dose, total V_12Gy and V_5Gy of uninvolved brain, number of monitor units (MUs), irradiation time and pass rate were compared. The GI was significantly higher for VMAT than for separate-isocenter, IMRT, and all automatically generated plans. The number of MUs was lowest for VMAT, followed by automatically generated DCA and IMRT plans and highest for manual DCA plans. Irradiation time was the shortest for automatically planned DCA plans. Automatically generated linac-based single-isocenter plans for multiple BM reduce the number of MUs and irradiation time with at least comparable GI and V_5Gy relative to the reference separate-isocenter DCA plans. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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13 pages, 553 KiB

Open AccessArticle

Predictors of Patient-Reported Incontinence at Adjuvant/Salvage Radiotherapy after Prostatectomy: Impact of Time between Surgery and Radiotherapy

by Fernando Munoz, Giuseppe Sanguineti, Andrea Bresolin, Domenico Cante, Vittorio Vavassori, Justina Magdalena Waskiewicz, Giuseppe Girelli, Barbara Avuzzi, Elisabetta Garibaldi, Adriana Faiella, Elisa Villa, Alessandro Magli, Barbara Noris Chiorda, Marco Gatti, Tiziana Rancati, Riccardo Valdagni, Nadia G. Di Muzio, Claudio Fiorino and Cesare Cozzarini

Cancers 2021, 13(13), 3243; https://doi.org/10.3390/cancers13133243 - 29 Jun 2021

Cited by 4 | Viewed by 1856

Abstract

Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it “as much as possible”, maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at [...] Read more.

Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it “as much as possible”, maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start. Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.gov #NCT02803086) aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss (ICIQ3 and ICIQ4, respectively), “objective” UI (ICIQ3 + 4), “subjective” UI (ICIQ5), and “TOTAL” UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression. Results: TTRT was the strongest predictor for all endpoints (p-values ≤ 0.001); all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency. Conclusions: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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12 pages, 492 KiB

Open AccessArticle

Efficacy and Safety of Hypofractionated Preoperative Radiotherapy for Primary Locally Advanced Soft Tissue Sarcomas of Limbs or Trunk Wall

by Hanna Koseła-Paterczyk, Paweł Teterycz, Mateusz J. Spałek, Aneta Borkowska, Anna Zawadzka, Michał Wągrodzki, Anna Szumera-Ciećkiewicz, Tadeusz Morysiński, Tomasz Świtaj, Iwona Ługowska, Patrycja Castaneda-Wysocka, Marcin Zdzienicki, Tomasz Goryń and Piotr Rutkowski

Cancers 2021, 13(12), 2981; https://doi.org/10.3390/cancers13122981 - 14 Jun 2021

Cited by 21 | Viewed by 2610

Abstract

Background: The use of adjuvant radiotherapy (RT) shows a significantly decreased incidence of local recurrence (LR) in soft tissue sarcomas (STS). This study aimed to assess the treatment scheme’s effect in patients with primary STS treated at one institution. Methods: In this phase [...] Read more.

Background: The use of adjuvant radiotherapy (RT) shows a significantly decreased incidence of local recurrence (LR) in soft tissue sarcomas (STS). This study aimed to assess the treatment scheme’s effect in patients with primary STS treated at one institution. Methods: In this phase 2 trial, 311 patients aged ≥18 years with primary, locally advanced STS of the extremity or trunk wall were assigned to multimodal therapy conducted at one institution. The preoperative RT scheme consisted of 5 Gy per fraction for a total dose of 25 Gy. Surgery was performed within 2–4 days from the last day of RT. The primary endpoint was LR-free survival (LRFS). Adverse events of the treatment were assessed. Results: We included 311 patients with primary locally advanced STS. The median tumor size was 11 cm. In total, 258 patients (83%) had high-grade tumors. In 260 patients (83.6%), clear surgical margins (R0) were obtained. Ninety-six patients (30.8%) had at least one type of treatment adverse event. LR was observed in 13.8% patients. The 5-year overall survival was 63%. Conclusion: In this group, with a significant percentage of patients with extensive, high-grade STS, hypofractionated preoperative RT was associated with good local control and tolerance. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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17 pages, 5088 KiB

Open AccessArticle

Management of Acute Radiodermatitis in Non-Melanoma Skin Cancer Patients Using Electrospun Nanofibrous Patches Loaded with Pinus halepensis Bark Extract

by Aikaterini Kyritsi, Stefanos Kikionis, Anna Tagka, Nikolaos Koliarakis, Antonia Evangelatou, Panagiotis Papagiannis, Alexandros Stratigos, Vangelis Karalis, Paraskevas Dallas, Andreas Vitsos, Efstathia Ioannou, Vassilios Roussis and Michail Rallis

Cancers 2021, 13(11), 2596; https://doi.org/10.3390/cancers13112596 - 26 May 2021

Cited by 14 | Viewed by 4080

Abstract

Acute radiodermatitis is the most common side effect in non-melanoma skin cancer patients undergoing radiotherapy. Nonetheless, despite the ongoing progress of clinical trials, no effective regimen has been found yet. In this study, a non-woven patch, comprised of electrospun polymeric micro/nanofibers loaded with [...] Read more.

Acute radiodermatitis is the most common side effect in non-melanoma skin cancer patients undergoing radiotherapy. Nonetheless, despite the ongoing progress of clinical trials, no effective regimen has been found yet. In this study, a non-woven patch, comprised of electrospun polymeric micro/nanofibers loaded with an aqueous extract of Pinus halepensis bark (PHBE), was fabricated and clinically tested for its efficacy to prevent radiodermatitis. The bioactivity of the PHBE patch was evaluated in comparison with a medical cream indicated for acute radiodermatitis. Twelve volunteer patients were selected and randomly assigned to two groups, applying either the PHBE patch or the reference cream daily. Evaluation of radiation-induced skin reactions was performed during the radiotherapy period and 1 month afterwards according to the Radiation Therapy Oncology Group (RTOG) grading scale, photo-documentation, patient-reported outcomes (Visual Analog Scale, questionnaire), biophysical measurements (hydration, transepidermal water loss, erythema, melanin), and image analysis. In contrast with the reference product, the PHBE patch showed significant anti-inflammatory activity and restored most skin parameters to normal levels 1 month after completion of radiation therapy. No adverse event was reported, indicating that the application of the PHBE patch can be considered as a safe medical device for prophylactic radiodermatitis treatment. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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19 pages, 16122 KiB

Open AccessArticle

Oxidative Stress-Dependent Synergistic Antiproliferation, Apoptosis, and DNA Damage of Ultraviolet-C and Coral-Derived Sinularin Combined Treatment for Oral Cancer Cells

by Sheng-Yao Peng, Jen-Yang Tang, Ruei-Nian Li, Hurng-Wern Huang, Chang-Yi Wu, Chien-Chih Chiu, Fang-Rong Chang, Hong-Wei Zhang, Yun-Jou Lee, Jyh-Horng Sheu and Hsueh-Wei Chang

Cancers 2021, 13(10), 2450; https://doi.org/10.3390/cancers13102450 - 18 May 2021

Cited by 9 | Viewed by 2692

Abstract

Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment [...] Read more.

Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment of UVC/sinularin has not been investigated as yet. This study aimed to examine the combined antiproliferation function and explore the combination of UVC/sinularin in oral cancer cells compared to normal oral cells. Regarding cell viability, UVC/sinularin displays the synergistic and selective killing of two oral cancer cell lines, but remains non-effective for normal oral cell lines compared to treatments in terms of MTS and ATP assays. In tests using the flow cytometry, luminescence, and Western blotting methods, UVC/sinularin-treated oral cancer cells exhibited higher reactive oxygen species production, mitochondrial superoxide generation, mitochondrial membrane potential destruction, annexin V, pan-caspase, caspase 3/7, and cleaved-poly (ADP-ribose) polymerase expressions than that in normal oral cells. Accordingly, oxidative stress and apoptosis are highly induced in a combined UVC/sinularin treatment. Moreover, UVC/sinularin treatment provides higher G2/M arrest and γH2AX/8-hydroxyl-2′deoxyguanosine-detected DNA damages in oral cancer cells than in the separate treatments. A pretreatment can revert all of these changes of UVC/sinularin treatment with the antioxidant N-acetylcysteine. Taken together, UVC/sinularin acting upon oral cancer cells exhibits a synergistic and selective antiproliferation ability involving oxidative stress-dependent apoptosis and cellular DNA damage with low toxic side effects on normal oral cells. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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18 pages, 1345 KiB

Open AccessArticle

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group

by Luciana Caravatta, Giovanna Mantello, Francesca Valvo, Pierfrancesco Franco, Lucrezia Gasparini, Consuelo Rosa, Najla Slim, Stefania Manfrida, Francesca De Felice, Marianna A. Gerardi, Stefano Vagge, Marco Krengli, Elisa Palazzari, Maria Falchetto Osti, Alessandra Gonnelli, Gianpiero Catalano, Patrizia Pittoni, Giovani Battista Ivaldi, Alessandra Galardi, Marco Lupattelli, Maria Elena Rosetto, Rita Marina Niespolo, Alessandra Guido, Oreste Durante, Gabriella Macchia, Fernando Munoz, Badr El khouzai, Maria Rosaria Lucido, Annamaria Porreca, Marta Di Nicola, Maria Antonietta Gambacorta, Vittorio Donato and Domenico Genovesi Show full author list Hide full author list

Cancers 2021, 13(8), 1902; https://doi.org/10.3390/cancers13081902 - 15 Apr 2021

Cited by 9 | Viewed by 2770

Abstract

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The [...] Read more.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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16 pages, 692 KiB

Open AccessArticle

Psychotherapy with Music Intervention Improves Anxiety, Depression and the Redox Status in Breast Cancer Patients Undergoing Radiotherapy: A Randomized Controlled Clinical Trial

by Patrizia Zeppegno, Marco Krengli, Daniela Ferrante, Marco Bagnati, Vincenzo Burgio, Serena Farruggio, Roberta Rolla, Carla Gramaglia and Elena Grossini

Cancers 2021, 13(8), 1752; https://doi.org/10.3390/cancers13081752 - 7 Apr 2021

Cited by 14 | Viewed by 4316

Abstract

The aim of this study was to assess the effects of psychotherapy with music intervention (PMI) on anxiety, depression, redox status, and inflammation in breast cancer patients undergoing radiotherapy (RT). This monocentric randomized clinical trial recruited 60 patients who had a breast cancer [...] Read more.

The aim of this study was to assess the effects of psychotherapy with music intervention (PMI) on anxiety, depression, redox status, and inflammation in breast cancer patients undergoing radiotherapy (RT). This monocentric randomized clinical trial recruited 60 patients who had a breast cancer operation and were undergoing postoperative RT. Eligible patients were randomized (1:1) in two groups: the control group (CG) received treatment as usual (n = 30), i.e., RT alone; the intervention group (PMI) received RT and psychotherapy with music intervention (n = 30), which was delivered in a group setting. Five patients were excluded after randomization. Assessments were performed at baseline (T0), at the end of RT (T1), and three months after the end of RT (T2). The main objectives of the study were the assessment of anxiety/depression, plasma glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in the two arms of the study. Our findings revealed a positive effect of PMI on anxiety, depression, resilience, and quality of life. Furthermore, a positive effect of PMI on redox status was found for the first time. Thus, in the PMI group, we found a significant increase of GSH (mean change 2.2 95%, CI 0.7 to 3.7) and a significant reduction of TBARS (mean change −1.1 95%, CI −1.8 to −0.3) at T2 vs. T0. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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14 pages, 2776 KiB

Open AccessArticle

Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy

by Kevin Chih-Yang Huang, Shu-Fen Chiang, Pei-Chen Yang, Tao-Wei Ke, Tsung-Wei Chen, Ching-Han Hu, Yi-Wen Huang, Hsin-Yu Chang, William Tzu-Liang Chen and K. S. Clifford Chao

Cancers 2021, 13(6), 1218; https://doi.org/10.3390/cancers13061218 - 11 Mar 2021

Cited by 24 | Viewed by 3035

Abstract

Rectal cancer accounts for 30–40% of colorectal cancer (CRC) and is the most common cancer-related death worldwide. The preoperative neoadjuvant chemoradiotherapy (neoCRT) regimen is the main therapeutic strategy for patients with locally advanced rectal cancer (LARC) to control tumor growth and reduce distant [...] Read more.

Rectal cancer accounts for 30–40% of colorectal cancer (CRC) and is the most common cancer-related death worldwide. The preoperative neoadjuvant chemoradiotherapy (neoCRT) regimen is the main therapeutic strategy for patients with locally advanced rectal cancer (LARC) to control tumor growth and reduce distant metastasis. However, 30–40% of patients achieve a partial response to neoCRT and suffer from unnecessary drug toxicity side effects and a risk of distant metastasis. In our study, we found that the novel topoisomerase I inhibitor lipotecan (TLC388) can elicit immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs), including HMGB1, ANXA1, and CRT exposure. Lipotecan thereby increases cancer immunogenicity and triggers an antitumor immune response to attract immune cell infiltration within the tumor microenvironment (TME) in vitro and in vivo. Taken together, these results show that lipotecan can remodel the tumor microenvironment to provoke anticancer immune responses, which can provide potential clinical benefits to the therapeutic efficacy of neoCRT in LARC patients. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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13 pages, 2159 KiB

Open AccessArticle

Dosimetric Validation of a GAN-Based Pseudo-CT Generation for MRI-Only Stereotactic Brain Radiotherapy

by Vincent Bourbonne, Vincent Jaouen, Clément Hognon, Nicolas Boussion, François Lucia, Olivier Pradier, Julien Bert, Dimitris Visvikis and Ulrike Schick

Cancers 2021, 13(5), 1082; https://doi.org/10.3390/cancers13051082 - 3 Mar 2021

Cited by 23 | Viewed by 2710

Abstract

Purpose: Stereotactic radiotherapy (SRT) has become widely accepted as a treatment of choice for patients with a small number of brain metastases that are of an acceptable size, allowing for better target dose conformity, resulting in high local control rates and better sparing [...] Read more.

Purpose: Stereotactic radiotherapy (SRT) has become widely accepted as a treatment of choice for patients with a small number of brain metastases that are of an acceptable size, allowing for better target dose conformity, resulting in high local control rates and better sparing of organs at risk. An MRI-only workflow could reduce the risk of misalignment between magnetic resonance imaging (MRI) brain studies and computed tomography (CT) scanning for SRT planning, while shortening delays in planning. Given the absence of a calibrated electronic density in MRI, we aimed to assess the equivalence of synthetic CTs generated by a generative adversarial network (GAN) for planning in the brain SRT setting. Methods: All patients with available MRIs and treated with intra-cranial SRT for brain metastases from 2014 to 2018 in our institution were included. After co-registration between the diagnostic MRI and the planning CT, a synthetic CT was generated using a 2D-GAN (2D U-Net). Using the initial treatment plan (Pinnacle v9.10, Philips Healthcare), dosimetric comparison was performed using main dose-volume histogram (DVH) endpoints in respect to ICRU 91 guidelines (Dmax, Dmean, D2%, D50%, D98%) as well as local and global gamma analysis with 1%/1 mm, 2%/1 mm and 2%/2 mm criteria and a 10% threshold to the maximum dose. t-test analysis was used for comparison between the two cohorts (initial and synthetic dose maps). Results: 184 patients were included, with 290 treated brain metastases. The mean number of treated lesions per patient was 1 (range 1–6) and the median planning target volume (PTV) was 6.44 cc (range 0.12–45.41). Local and global gamma passing rates (2%/2 mm) were 99.1 CI95% (98.1–99.4) and 99.7 CI95% (99.6–99.7) respectively (CI: confidence interval). DVHs were comparable, with no significant statistical differences regarding ICRU 91′s endpoints. Conclusions: Our study is the first to compare GAN-generated CT scans from diagnostic brain MRIs with initial CT scans for the planning of brain stereotactic radiotherapy. We found high similarity between the planning CT and the synthetic CT for both the organs at risk and the target volumes. Prospective validation is under investigation at our institution. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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13 pages, 999 KiB

Open AccessFeature PaperArticle

The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation

by Margherita Rimini, Pierfrancesco Franco, Berardino De Bari, Maria Giulia Zampino, Stefano Vagge, Giovanni Luca Frassinetti, Francesca Arcadipane, Almalina Bacigalupo, Martina Valgiusti, Deborah Aloi, Lorenzo Gervaso, Renzo Corvò, Giulia Bartolini, Marianna Alessandra Gerardi, Stefano Cascinu and Andrea Casadei-Gardini

Cancers 2021, 13(4), 671; https://doi.org/10.3390/cancers13040671 - 7 Feb 2021

Cited by 8 | Viewed by 4846

Abstract

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) [...] Read more.

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04–5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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10 pages, 1451 KiB

Open AccessArticle

Feasibility and Safety of Repeated Carbon Ion Radiotherapy for Locally Advanced Unresectable Pancreatic Cancer

by Masahiko Okamoto, Shintaro Shiba, Shohei Okazaki, Yuhei Miyasaka, Kei Shibuya, Hiroki Kiyohara and Tatsuya Ohno

Cancers 2021, 13(4), 665; https://doi.org/10.3390/cancers13040665 - 7 Feb 2021

Cited by 6 | Viewed by 2076

Abstract

Purpose: The feasibility and safety of re-irradiation with carbon ion beams for locally recurrent unresectable pancreatic cancer (URPC) after carbon ion radiotherapy (CIRT) was evaluated. Methods: Medical records from patients with re-irradiated URPC who were treated with CIRT between November 2017 and February [...] Read more.

Purpose: The feasibility and safety of re-irradiation with carbon ion beams for locally recurrent unresectable pancreatic cancer (URPC) after carbon ion radiotherapy (CIRT) was evaluated. Methods: Medical records from patients with re-irradiated URPC who were treated with CIRT between November 2017 and February 2019 were reviewed. Inclusion criteria were (1) isolated local recurrence after CIRT, (2) URPC, and (3) tumor located at least 3 mm from the gastrointestinal tract. The first and second CIRT irradiation doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Results: Ten patients met the inclusion criteria. The median follow-up period was 25.5 months (range, 16.0–69.1) after the first CIRT and 8.9 months (range, 6.4–18.9) after the second CIRT. The median interval between the initial CIRT and the local recurrence was 15.8 months (range, 8.0–50.1). One patient developed grade 3 diarrhea immediately after the second CIRT; no other grade 3 or higher adverse events were attributed to CIRT. The estimated 1-year overall survival, local control, and progression-free survival rates after the second CIRT were 48%, 67%, and 34%, respectively. Conclusion: Repeated CIRT is feasible with acceptable toxicity for selected patients with locally advanced URPC after CIRT. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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10 pages, 955 KiB

Open AccessArticle

Rectal Dose Is the Other Dosimetric Factor in Addition to Small Bowel for Prediction of Acute Diarrhea during Postoperative Whole-Pelvic Intensity-Modulated Radiotherapy in Gynecologic Patients

by Eng-Yen Huang, Yu-Ming Wang, Shih-Chen Chang, Shu-Yu Liu and Ming-Chung Chou

Cancers 2021, 13(3), 497; https://doi.org/10.3390/cancers13030497 - 28 Jan 2021

Cited by 3 | Viewed by 1933

Abstract

We studied the association of rectal dose with acute diarrhea in patients with gynecologic malignancies undergoing whole-pelvic (WP) intensity-modulated radiotherapy (IMRT). From June 2006 to April 2019, 108 patients with previous hysterectomy who underwent WP IMRT were enrolled in this cohort study. WP [...] Read more.

We studied the association of rectal dose with acute diarrhea in patients with gynecologic malignancies undergoing whole-pelvic (WP) intensity-modulated radiotherapy (IMRT). From June 2006 to April 2019, 108 patients with previous hysterectomy who underwent WP IMRT were enrolled in this cohort study. WP irradiation of 39.6–45 Gy/22–25 fractions was initially delivered to the patients. Common Terminology Criteria for Adverse Events (CTCAE) version 3 was used to evaluate acute diarrhea during radiotherapy. Small bowel volume at different levels of isodose curves (Vn%) and mean rectal dose (MRD) were measured for statistical analysis. The multivariate analysis showed that the MRD ≥ 32.75 Gy (p = 0.005) and small bowel volume of 100% prescribed (V100%) ≥ 60 mL (p = 0.008) were independent factors of Grade 2 or higher diarrhea. The cumulative incidence of Grade 2 or higher diarrhea at 39.6 Gy were 70.5%, 42.2%, and 15.0% (p < 0.001) in patients with both high (V100% ≥ 60 mL and MRD ≥ 32.75 Gy), either high, and both low volume-dose factors, respectively. Strict constraints for the rectum/small bowel or image-guided radiotherapy to reduce these doses are suggested. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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10 pages, 1227 KiB

Open AccessArticle

Single-Fraction Adjuvant Electronic Brachytherapy after Resection of Conjunctival Carcinoma

by Gustavo R. Sarria, Solon Serpa, Mario Buitrago, Paola Fuentes Rivera, Diego Ramirez, Frank A. Giordano and Gustavo J. Sarria

Cancers 2021, 13(3), 454; https://doi.org/10.3390/cancers13030454 - 26 Jan 2021

Viewed by 3890

Abstract

A retrospective study was performed to assess the outcomes of a single-fraction adjuvant electronic brachytherapy (e-BT) approach for patients with squamous cell conjunctival carcinoma (SCCC). Forty-seven patients with T1–T3 SCCC were included. All patients underwent surgery followed by a single-fraction adjuvant e-BT with [...] Read more.

A retrospective study was performed to assess the outcomes of a single-fraction adjuvant electronic brachytherapy (e-BT) approach for patients with squamous cell conjunctival carcinoma (SCCC). Forty-seven patients with T1–T3 SCCC were included. All patients underwent surgery followed by a single-fraction adjuvant e-BT with a porTable 50-kV device. Depending on margins, e-BT doses ranged between 18 to 22 Gy prescribed at 2 mm depth, resembling equivalent doses in 2 Gy (EQD2) per fraction of 46–66 Gy (α/β ratio of 8–10 Gy and a relative biological effect (RBE) of 1.3). The median age was 69 (29–87) years. Most tumors were T1 (40.4%) or T2 (57.5%) with a median size of 7 mm (1.5–20). Margins were positive in 40.4% of cases. The median time from surgery to e-BT was nine weeks (0–37). After a median follow-up of 24 (17–40) months, recurrence occurred in only two patients (6 and 7 months after e-BT), yielding a median disease-free survival (DFS) of 24 (6–40) months and DFS at two years of 95.7%. Acute grade 2 conjunctivitis occurred in 25.5%. E-BT is a safe and effective for SCCC treatment, with clinical and logistic advantages compared to classical methods. Longer follow-up and prospective assessment are warranted. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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11 pages, 600 KiB

Open AccessArticle

Impact of Radiotherapy on Kidney Function among Patients Who Received Adjuvant Treatment for Gastric Cancer: Logistic and Linear Regression Analyses

by Jun Su Park, Jeong Il Yu, Do Hoon Lim, Heerim Nam, Young Il Kim, Jeeyun Lee, Won Ki Kang, Se Hoon Park, Seung Tae Kim, Jung Yong Hong, Tae Sung Sohn, Jun Ho Lee, Ji Yeong An, Min Gew Choi and Jae Moon Bae

Cancers 2021, 13(1), 59; https://doi.org/10.3390/cancers13010059 - 28 Dec 2020

Cited by 7 | Viewed by 2753

Abstract

We investigated the incidence of renal function impairment after adjuvant treatment for gastric cancer and analyzed the impact of radiotherapy on estimated glomerular filtration rate (eGFR) five years after gastric surgery. We reviewed the medical records of 1490 patients with stomach cancer who [...] Read more.

We investigated the incidence of renal function impairment after adjuvant treatment for gastric cancer and analyzed the impact of radiotherapy on estimated glomerular filtration rate (eGFR) five years after gastric surgery. We reviewed the medical records of 1490 patients with stomach cancer who underwent curative surgery and adjuvant treatment for gastric cancer. Finally, we included 663 patients who were followed up for ≥5 years without disease recurrence and whose baseline eGFR was ≥60 mL/min/1.73 m². Logistic and linear regression analyses were performed to determine independent factors associated with the five-year eGFR. A total of 13 (2.0%) patients developed renal function impairment (five-year eGFR <60 mL/min/1.73 m²). In logistic regression analysis, the baseline eGFR was identified as a prognostic factor for renal function impairment (odds ratio (OR), 0.878; 95% confidence interval (CI), 0.831–0.927; p < 0.001), but radiotherapy was not (OR, 1.130; 95% CI, 0.366–3.491; p = 0.832). In linear regression analysis, age (B = −0.350, p < 0.001), baseline eGFR (B = 0.576, p < 0.001), cisplatin (B = −2.056, p = 0.010), and radiotherapy (B = −2.628, p < 0.001) were predictive variables for the five-year eGFR. Among patients who received adjuvant radiotherapy, age (B = −0.277, p < 0.001), hypertension (B = −4.986, p = 0.004), baseline eGFR (B = 0.665, p < 0.001), and volume of the kidneys receiving ≥20 Gy (B = −0.209, p = 0.012) were predictive variables for the five-year eGFR. Development of renal function impairment after adjuvant treatment for gastric cancer was rare among patients with normal baseline kidney function. While radiotherapy was negatively associated with the five-year eGFR, its impact would have been minimal if the kidneys were properly shielded. Further studies are needed to confirm the impact of radiotherapy in patients with poor kidney function. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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12 pages, 281 KiB

Open AccessArticle

Multidisciplinary Management of Radiation-Induced Salivary Gland Carcinomas in the Modern Radiotherapy Era

by Domenico Attilio Romanello, Zulfiyya Imamguliyeva, Stefano Cavalieri, Barbara Vischioni, Lorenza Gandola, Alberto Iannalfi, Nicola Alessandro Iacovelli, Lisa Licitra, Marco Guzzo, Cesare Piazza, Davide Lombardi, Barbara Diletto, Pasquale Quattrone, Giuseppina Calareso, Laura Deborah Locati and Ester Orlandi

Cancers 2020, 12(12), 3769; https://doi.org/10.3390/cancers12123769 - 14 Dec 2020

Cited by 2 | Viewed by 2098

Abstract

Clinical data of ri-SGCs patients treated between 2015 and 2019 at a tertiary cancer center and a national hadron therapy facility were reviewed. Latent time (LT) from first RT to ri-SGCs diagnosis, overall (OS), and disease-free survival (DFS) were assessed. Thirteen patients developed [...] Read more.

Clinical data of ri-SGCs patients treated between 2015 and 2019 at a tertiary cancer center and a national hadron therapy facility were reviewed. Latent time (LT) from first RT to ri-SGCs diagnosis, overall (OS), and disease-free survival (DFS) were assessed. Thirteen patients developed 14 ri-SGCs (one patient had 2 synchronous ri-SCGs), after a median LT of 23 years (range 16–34). Parotid was the primary site in 8 cases (57%) and salivary duct carcinoma was the most frequent histotype (29%). Nine patients (69%) underwent surgery (Sx). Among them, 4 patients (31%) underwent Sx alone, 5 received post-operative treatments: 3 (23%) photon-based (X) reRT, one (8%) protons and carbon ions, one (8%) carbon ions only. One patient (8%) received definitive XRT. The remaining 3 patients (23%) received androgen deprivation therapy. With a median follow-up of 48 months (range 24–72), median OS and PFS were 74 and 24 months, respectively. In the subgroup of AR⁺ ri-SGCs, median PFS and OS were 12 and 74 months, respectively. Given the rarity of ri-SGCs, this work adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

13 pages, 1301 KiB

Open AccessArticle

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis

by Nina-Sophie Schmidt Hegemann, Paul Rogowski, Chukwuka Eze, Christian Schäfer, Christian Stief, Sebastian Lang, Simon Spohn, Rieke Steffens, Minglun Li, Christian Gratzke, Wolfgang Schultze-Seemann, Harun Ilhan, Wolfgang Peter Fendler, Peter Bartenstein, Ute Ganswindt, Alexander Buchner, Anca-Ligia Grosu, Claus Belka, Philipp Tobias Meyer, Simon Kirste and Constantinos Zamboglou Show full author list Hide full author list

Cancers 2020, 12(11), 3395; https://doi.org/10.3390/cancers12113395 - 16 Nov 2020

Cited by 11 | Viewed by 2485

Abstract

The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is [...] Read more.

The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is based on 421 patients referred for PSMA or choline PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. BRFS (PSA: 0.2 ng/mL) was defined as the study endpoint. Cox regression analyses were performed to assess the impact of different clinical parameters on BRFS. Additionally, propensity score matching was performed to adjust patient cohorts (PSMA vs. choline PET/CT-based sRT). The median follow-up time was 30 months. BRFS at three years after sRT was 58%. In the multivariate analysis, only PSA before PET imaging and PSA before sRT were significantly associated with BRFS (p < 0.05). After propensity score matching, 272 patients were further analyzed; there was no significant difference in three-year BRFS between patients with PSMA PET-based vs. choline PET-based sRT (55% vs. 63%, p = 0.197). The present analysis confirmed the overall high BRFS rates after PET-based sRT and the strong prognostic effect of PSA level prior to sRT. PSMA PET-based sRT did not have superior BRFS rates when compared with choline PET-based sRT. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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17 pages, 1381 KiB

Open AccessArticle

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial

by Francesca Arcadipane, Patrick Silvetti, Francesco Olivero, Alessio Gastino, Viola De Luca, Massimiliano Mistrangelo, Paola Cassoni, Patrizia Racca, Elena Gallio, Adriana Lesca, Christian Fiandra, Umberto Ricardi and Pierfrancesco Franco

Cancers 2020, 12(11), 3306; https://doi.org/10.3390/cancers12113306 - 9 Nov 2020

Cited by 21 | Viewed by 2690

Abstract

Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with ¹⁸FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage [...] Read more.

Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with ¹⁸FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon’s design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed ¹⁸FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: ¹⁸FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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10 pages, 838 KiB

Open AccessArticle

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer

by Michele Fiore, Silvia Taralli, Pasquale Trecca, Valentina Scolozzi, Luca Marinelli, Elizabeth K. A. Triumbari, Damiano Caputo, Silvia Angeletti, Massimo Ciccozzi, Alessandro Coppola, Carlo Greco, Edy Ippolito, Maria Lucia Calcagni, Roberto Coppola and Sara Ramella

Cancers 2020, 12(8), 2016; https://doi.org/10.3390/cancers12082016 - 23 Jul 2020

Cited by 7 | Viewed by 2185

Abstract

Purpose: To evaluate the predictive value of ¹⁸F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our [...] Read more.

Purpose: To evaluate the predictive value of ¹⁸F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline ¹⁸F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline ¹⁸F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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Review

Jump to: Research

19 pages, 745 KiB

Open AccessReview

Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy

by Maria Grazia Ronga, Marco Cavallone, Annalisa Patriarca, Amelia Maia Leite, Pierre Loap, Vincent Favaudon, Gilles Créhange and Ludovic De Marzi

Cancers 2021, 13(19), 4942; https://doi.org/10.3390/cancers13194942 - 30 Sep 2021

Cited by 47 | Viewed by 4710

Abstract

The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such [...] Read more.

The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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14 pages, 824 KiB

Open AccessReview

Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know?

by Stephanie T. H. Peeters, Evert J. Van Limbergen, Lizza E. L. Hendriks and Dirk De Ruysscher

Cancers 2021, 13(9), 2132; https://doi.org/10.3390/cancers13092132 - 28 Apr 2021

Cited by 5 | Viewed by 3175

Abstract

Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which [...] Read more.

Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called “oligometastatic” is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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23 pages, 2372 KiB

Open AccessReview

Breast Radiotherapy-Related Cardiotoxicity. When, How, Why. Risk Prevention and Control Strategies

by Ana Aurora Díaz-Gavela, Lourdes Figueiras-Graillet, Ángel Montero Luis, Juliana Salas Segura, Raquel Ciérvide, Elia del Cerro Peñalver, Felipe Couñago, Meritxell Arenas and Teresa López-Fernández

Cancers 2021, 13(7), 1712; https://doi.org/10.3390/cancers13071712 - 4 Apr 2021

Cited by 27 | Viewed by 6542

Abstract

In recent decades, improvements in breast cancer management have increased overall patient survival; however, many cancer therapies have been linked to an important risk of cardiovascular adverse events. Cardio-oncology has been proposed as an emerging specialty to coordinate preventive strategies that improve the [...] Read more.

In recent decades, improvements in breast cancer management have increased overall patient survival; however, many cancer therapies have been linked to an important risk of cardiovascular adverse events. Cardio-oncology has been proposed as an emerging specialty to coordinate preventive strategies that improve the cardiovascular health of oncologic patients. It employs the most suitable personalized multidisciplinary management approach for each patient to optimize their cardiovascular health and improve their survival and quality of life. Radiotherapy is an essential part of the therapeutic regimen in breast cancer patients but can also increase the risk of cardiovascular disease. Therefore, minimizing the negative impact of radiation therapy is an important challenge for radiotherapy oncologists and cardiologists specializing in this field. The aim of the present review is to update our knowledge about radiation-induced cardiotoxicity in breast cancer patients by undertaking a critical review of the relevant literature to determine risk prevention and control strategies currently available. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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29 pages, 1048 KiB

Open AccessReview

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

by Damiënne Marcus, Relinde I. Y. Lieverse, Carmen Klein, Amir Abdollahi, Philippe Lambin, Ludwig J. Dubois and Ala Yaromina

Cancers 2021, 13(6), 1468; https://doi.org/10.3390/cancers13061468 - 23 Mar 2021

Cited by 31 | Viewed by 4907

Abstract

Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by [...] Read more.

Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by stereotactic body radiation therapy (SBRT), are increasingly investigated in combination with cancer immunotherapy within clinical trials. Despite intensive preclinical studies, the optimal dose per fraction and dose schemes for elaboration of RT induced immunogenic potential remain inconclusive. Compared to the scenario of combined immune checkpoint inhibition (ICI) and RT, multimodal therapies utilizing other immunotherapy principles such as adoptive transfer of immune cells, vaccination strategies, targeted immune-cytokines and agonists are underrepresented in both preclinical and clinical settings. Despite the clinical success of ICI and RT combination, e.g., prolonging overall survival in locally advanced lung cancer, curative outcomes are still not achieved for most cancer entities studied. Charged particle RT (PRT) has gained interest as it may enhance tumor immunogenicity compared to conventional RT due to its unique biological and physical properties. However, whether PRT in combination with immune therapy will elicit superior antitumor effects both locally and systemically needs to be further investigated. In this review, the immunological effects of RT in the tumor microenvironment are summarized to understand their implications for immunotherapy combinations. Attention will be given to the various immunotherapeutic interventions that have been co-administered with RT so far. Furthermore, the theoretical basis and first evidences supporting a favorable immunogenicity profile of PRT will be examined. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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20 pages, 1127 KiB

Open AccessReview

Immunoradiotherapy as an Effective Therapeutic Strategy in Lung Cancer: From Palliative Care to Curative Intent

by Rodolfo Chicas-Sett, Juan Zafra-Martin, Ignacio Morales-Orue, Juan Castilla-Martinez, Miguel A. Berenguer-Frances, Elisa Gonzalez-Rodriguez, Delvys Rodriguez-Abreu and Felipe Couñago

Cancers 2020, 12(8), 2178; https://doi.org/10.3390/cancers12082178 - 5 Aug 2020

Cited by 25 | Viewed by 5300

Abstract

Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), [...] Read more.

Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), the treatment of metastatic and locally advanced non-small cell lung cancer (NSCLC) has experienced a revolution that has resulted in a significant improvement in overall survival with an enhanced toxicity profile. Despite this paradigm shift, most patients present some kind of resistance to ICI. In this setting, current research is shifting towards the integration of multiple therapies, with RT and ICI being one of the most promising based on the potential immunostimulatory synergy of this combination. This review gives an overview of the evolution and current state of the combination of RT and ICI and provides evidence-based data that can improve patient selection. The combination in lung cancer is a safe therapeutic approach that improves local control and progression-free survival, and it has the potential to unleash abscopal responses. Additionally, this treatment strategy seems to be able to re-sensitize select patients that have reached a state of resistance to ICI, further enabling the continuation of systemic therapy. Full article

(This article belongs to the Special Issue Cancer Radiotherapy)

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