Radiation Oncology

Wang, Weiping; Hu, Ke; Qiu, Jie; Zhang, Fuquan

2020 Radiation Oncology

doi: 10.1186/s13014-020-01612-5pmid: 32646454

The daily new confirmed Coronavirus disease 2019 (COVID-19) cases have decreased in some European and Asian countries. Many countries and areas have started to ease public restrictions. Here, we share our experiences and recommendations on how to conduct radiotherapy after public restrictions have eased or upon reopening. Firstly, COVID-19 nucleic acid test screening should be performed for all new admitted patients in areas with enough test capability. Secondly, radiotherapy can be conducted reference to consensus or recommendations on radiotherapy during COVID-19. Thirdly, it is not the time to consider compromising the guidance and the guidance on radiotherapy workflow and protection procedures still should be strictly followed.

Algara López, Manuel; Rodríguez García, Elvira; Beato Tortajada, Inmaculada; Martínez Arcelus, Francisco José; Salinas Ramos, Juan; Rodríguez garrido, José Reyes; Sanz Latiesas, Xavier; Soler Rodríguez, Ana; Juan Rijo, Germán; Flaquer García, Amanda

2020 Radiation Oncology

doi: 10.1186/s13014-020-01672-7pmid: 33008422

BackgroundConservative surgery followed by breast and nodal irradiation is the standard loco-regional early breast cancer (BC) treatment for patients with four or more involved lymph nodes. However, the treatment strategy when fewer nodes are involved remains unclear, especially when lymphadenectomy has not been performed. Sensitive nodal status assessment molecular techniques as the One-Step Nucleic Acid Amplification (OSNA) assay can contribute to the definition and standardization of the treatment strategy. Therefore, the OPTIMAL study aims to demonstrate the feasibility of incidental irradiation of axillary nodes in patients with early-stage BC and limited involvement of the SLN.MethodsBC patients who underwent conservative surgery and whose SLN total tumour load assessed with OSNA ranged between 250–15,000 copies/µL will be eligible. Patients will be randomized to receive irradiation on the breast, tumour bed, axillary and supraclavicular lymph node areas (intentional arm) or only on the breast and tumour bed (incidental arm). All areas, including the internal mammary chain, will be contoured. The mean, median, D5% and D95% doses received in all volumes will be calculated. The primary endpoint is the non-inferiority of the incidental irradiation of axillary nodes compared to the intentional irradiation in terms of 5-year disease free survival. Secondary endpoints comprise the comparison of acute and chronic toxicity and loco-regional and distant disease recurrence rates.DiscussionStandardizing the treatment and diagnosis of BC patients with few nodes affected is crucial due to the lack of consensus. Hence, the quantitative score for the metastatic burden of SLN provided by OSNA can contribute by improving the discrimination of which BC patients with limited nodal involvement can benefit from incidental radiation as an adjuvant treatment strategy.Trial registrationClinicalTrial.gov, NCT02335957; https://clinicaltrials.gov/ct2/show/NCT02335957

Moore, Sara; Leung, Bonnie; Wu, Jonn; Ho, Cheryl

2020 Radiation Oncology

doi: 10.1186/s13014-020-1466-ypmid: 32000829

ObjectivesCurative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome.Materials and methodsA retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention.ResultsA total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose > = 60Gy were associated with improved outcomes.ConclusionsAmong patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population.

Jin, Liang; Shi, Ning; Ruan, Shiye; Hou, Baohua; Zou, Yiping; Zou, Xiongfeng; Jin, Haosheng; Jian, Zhixiang

2020 Radiation Oncology

doi: 10.1186/s13014-020-01511-9pmid: 32272945

PurposeSeveral studies investigating the role of intraoperative radiotherapy (IORT) in the treatment of resectable pancreatic cancer (PC) have been published; however, their results remain inconsistent. By conducting a systematic review and meta-analysis, this study aimed to compare clinical outcomes in patients with resectable PC who underwent surgery with or without IORT.Methods and materialsThe MEDLINE/PubMed, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to February 28, 2019. The main outcome measures included median survival time (MST), local recurrence (LR), postoperative complications, and operation-related mortality. Pooled effect estimates were obtained by performing a random-effects meta-analysis.ResultsA total of 1095 studies were screened for inclusion, of which 15 studies with 834 patients were included in the meta-analysis. Overall, 401 patients underwent pancreatic resection with IORT and 433 underwent surgery without IORT. The pooled analysis revealed that IORT group experienced favorable overall survival (median survival rate [MSR], 1.20; 95% confidence interval [CI], 1.06–1.37, P = 0.005), compared with patients who did not receive IORT. Additionally, the pooled data showed a significantly reduced LR rate in the IORT group compared with that in the non-IORT group (relative risk [RR], 0.70; 95% CI, 0.51–0.97, P = 0.03). The incidences of postoperative complications (RR, 0.95; 95% CI, 0.73–1.23) and operation-related mortality (RR, 1.07; 95% CI, 0.44–2.63) were similar between the IORT and non-IORT groups.ConclusionIORT significantly improved locoregional control and overall survival in patients with resectable PC, without increasing postoperative complications and operation-related mortality rates.

Binkley, Michael S.; Koenig, Julie L.; Kashyap, Mehr; Xiang, Michael; Liu, Yufei; Sodji, Quaovi; Maxim, Peter G.; Diehn, Maximilian; Loo, Billy W.; Gensheimer, Michael F.

2020 Radiation Oncology

doi: 10.1186/s13014-020-01546-ypmid: 32429982

BackgroundWe evaluated whether pre- and mid-treatment metabolic tumor volume (MTV) predicts per lesion local recurrence (LR) in patients treated with definitive radiation therapy (RT, dose≥60 Gy) for locally advanced non-small cell lung cancer (NSCLC).MethodsWe retrospectively reviewed records of patients with stage III NSCLC treated from 2006 to 2018 with pre- and mid-RT PET-CT. We measured the MTV of treated lesions on the pre-RT (MTVpre) and mid-RT (MTVmid) PET-CT. LR was defined per lesion as recurrence within the planning target volume. Receiver operating characteristic (ROC) curves, cumulative incidence rates, and uni- and multivariable (MVA) competing risk regressions were used to evaluate the association between MTV and LR.ResultsWe identified 111 patients with 387 lesions (112 lung tumors and 275 lymph nodes). Median age was 68 years, 69.4% were male, 46.8% had adenocarcinoma, 39.6% had squamous cell carcinoma, and 95.5% received concurrent chemotherapy. Median follow-up was 38.7 months. 3-year overall survival was 42.3%. 3-year cumulative incidence of LR was 26.8% per patient and 11.9% per lesion. Both MTVpre and MTVmid were predictive of LR by ROC (AUC = 0.71 and 0.76, respectively) and were significantly associated with LR on MVA (P = 0.004 and P = 7.1e-5, respectively). Among lesions at lower risk of LR based on MTVpre, higher MTVmid was associated with LR (P = 0.001).ConclusionPer-lesion, larger MTVpre and MTVmid predicted for increased risk of LR. MTVmid was more highly predictive of LR than MTVpre and if validated may allow for further discrimination of high-risk lesions at mid-RT informing dose painting strategies.

Kim, Nalee; Kim, Se Hoon; Kang, Seok-Gu; Moon, Ju Hyung; Cho, Jaeho; Suh, Chang-Ok; In Yoon, Hong; Chang, Jong Hee

2020 Radiation Oncology

doi: 10.1186/s13014-020-01619-ypmid: 32736562

BackgroundTo identify the association between somatic ataxia-telangiectasia mutated (ATM) mutations and improved radio-sensitivity, we retrospectively reviewed next-generation sequencing data from patients diagnosed with isocitrate dehydrogenase (IDH)-wildtype high-grade glioma.MethodsWe included 39 individuals with (IDH)-wildtype high-grade glioma (diffuse astrocytoma n = 2, anaplastic astrocytoma n = 10, and glioblastoma n = 27) not subjected to gross tumor resection and undergoing radiation therapy with a median total dose of 60 Gy in 30 fractions. The mutational status of the ATM gene was obtained through next-generation sequencing using a TruSight Tumor 170 cancer panel. Disease progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria as well as neurologic and clinical findings.ResultsAmong the 39 samples, ATM mutations (ATM mut(+)) were detected in 26% of cases (n = 10). No significant differences were observed in the characteristics of the patients or tumors. Among the 10 patients in the ATM mut(+) group, there were 6 patients with glioblastoma and 4 patients with anaplastic astrocytoma. Most mutations were missense mutations (n = 8, 80%). With a median follow-up of 16.5 mo (interquartile range, 11.4–19.8), ATM mut(+) exhibited 1-year in-field control of 100% compared with 44.1% in the ATM mut(−) group (p = 0.002). There was no difference in the out-field control rate or overall survival between the two groups (p = 0.861 and p = 0.247, respectively).ConclusionsOur results demonstrated that ATM mutations might be involved in the increased radio-sensitivity with excellent in-field control despite the aggressive nature of IDH-wildtype high-grade glioma. Further studies are necessary to uncover the potential role of ATM as a biomarker and candidate therapeutic target in high-grade gliomas.

Remick, Jill S.; Kowalski, Emily; Khairnar, Rahul; Sun, Kai; Morse, Emily; Cherng, Hua-Ren R.; Poirier, Yannick; Lamichhane, Narottam; Becker, Stewart J.; Chen, Shifeng; Patel, Akshar N.; Kwok, Young; Nichols, Elizabeth; Mohindra, Pranshu; Woodworth, Graeme F.; Regine, William F.; Mishra, Mark V.

2020 Radiation Oncology

doi: 10.1186/s13014-020-01522-6pmid: 32466775

BackgroundHypofractionated-SRS (HF-SRS) may allow for improved local control and a reduced risk of radiation necrosis compared to single-fraction-SRS (SF-SRS). However, data comparing these two treatment approaches are limited. The purpose of this study was to compare clinical outcomes between SF-SRS versus HF-SRS across our multi-center academic network.MethodsPatients treated with SF-SRS or HF-SRS for brain metastasis from 2013 to 2018 across 5 radiation oncology centers were retrospectively reviewed. SF-SRS dosing was standardized, whereas HF-SRS dosing regimens were variable. The co-primary endpoints of local control and radiation necrosis were estimated using the Kaplan Meier method. Multivariate analysis using Cox proportional hazards modeling was performed to evaluate the impact of select independent variables on the outcomes of interest. Propensity score adjustments were used to reduce the effects confounding variables. To assess dose response for HF-SRS, Biologic Effective Dose (BED) assuming an α/β of 10 (BED10) was used as a surrogate for total dose.ResultsOne-hundred and fifty six patients with 335 brain metastasis treated with SF-SRS (n = 222 lesions) or HF-SRS (n = 113 lesions) were included. Prior whole brain radiation was given in 33% (n = 74) and 34% (n = 38) of lesions treated with SF-SRS and HF-SRS, respectively (p = 0.30). After a median follow up time of 12 months in each cohort, the adjusted 1-year rate of local control and incidence of radiation necrosis was 91% (95% CI 86–96%) and 85% (95% CI 75–95%) (p = 0.26) and 10% (95% CI 5–15%) and 7% (95% CI 0.1–14%) (p = 0.73) for SF-SRS and HF-SRS, respectively. For lesions > 2 cm, the adjusted 1 year local control was 97% (95% CI 84–100%) for SF-SRS and 64% (95% CI 43–85%) for HF-SRS (p = 0.06). On multivariate analysis, SRS fractionation was not associated with local control and only size ≤2 cm was associated with a decreased risk of developing radiation necrosis (HR 0.21; 95% CI 0.07–0.58, p < 0.01). For HF-SRS, 1 year local control was 100% for lesions treated with a BED10 ≥ 50 compared to 77% (95% CI 65–88%) for lesions that received a BED10 < 50 (p = 0.09).ConclusionsIn this comparison study of dose fractionation for the treatment of brain metastases, there was no difference in local control or radiation necrosis between HF-SRS and SF-SRS. For HF-SRS, a BED10 ≥ 50 may improve local control.

Júnior, Luiz Henrique Ferreira; Limirio, Pedro Henrique Justino Oliveira; Soares, Priscilla Barbosa Ferreira; Dechichi, Paula; de Souza Castro Filice, Letícia; Quagliatto, Paulo Sérgio; Rocha, Flaviana Soares

2020 Radiation Oncology

doi: 10.1186/s13014-020-01542-2pmid: 32375798

BackgroundRadiotherapy used in tumor treatment compromises vascularization of bone tissue. Hyperbaric oxygenation (HBO) increases oxygen availability and improves vascularization, minimizing the deleterious effects of ionizing radiation (IR). Therefore, the aim of this study was to evaluate HBO therapy effect on bone macroscopy, composition and biomechanical properties after IR damage.MethodsTwenty male Wistar rats weighing 300 ± 20 g (10 weeks of age) were submitted to IR (30 Gy) to the left leg, where the right leg was not irradiated. After 30 days, ten animals were submitted to HBO therapy, which was performed daily for 1 week at 250 kPa for 90-min sessions. All animals were euthanized 37 days after irradiation and the tibia were separated into four groups (n = 10): from animals without HBO - right tibia Non-irradiated (noIRnoHBO) and left tibia Irradiated (IRnoHBO); and from animals with HBO - right tibiae Non-irradiated (noIRHBO) and left tibia Irradiated (IRHBO). The length (proximal-distal) and thickness (anteroposterior and mediolateral) of the tibiae were measured. Biomechanical analysis evaluated flexural strength and stiffness. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) was used to calculate the amide I ratio, crystallinity index, and matrix to mineral ratios.ResultsIn the macroscopic and ATR-FTIR analysis, the IRnoHBO showed lower values of length, thickness and amide I ratio, crystallinity index and matrix to mineral ratios compared to noIRnoHBO (p < 0.03). IRnoHBO showed no statistical difference compared to IRHBO for these analyses (p > 0.05). Biomechanics analysis showed that the IRnoHBO group had lower values of flexural strength and stiffness compared to noIRnoHBO and IRHBO groups (p < 0.04). In addition, the noIRHBO group showed higher value of flexural strength when compared to noIRnoHBO and IRHBO groups (p < 0.02).ConclusionsThe present study concluded that IR arrests bone development, decreases the collagen maturation and mineral deposition process, thus reducing the flexural strength and stiffness bone mechanical parameters. Moreover, HBO therapy minimizes deleterious effects of irradiation on flexural strength and the bone stiffness analysis.

Kowalchuk, Roman O.; Waters, Michael R.; Richardson, K. Martin; Spencer, Kelly; Larner, James M.; Irvin, William P.; Kersh, Charles R.

2020 Radiation Oncology

doi: 10.1186/s13014-020-01564-wpmid: 32404167

BackgroundThis study evaluates the outcomes and toxicity of stereotactic body radiation therapy (SBRT) in ovarian cancer.MethodsThis retrospective analysis considered all patients treated with SBRT from 2009 to 2018 with a primary ovarian tumor. Follow-up included PET-CT and CT scans at 2–3 month intervals. Statistical analysis primarily consisted of univariate analysis, Cox proportional hazards analysis, and the Kaplan-Meier method.ResultsThe study included 35 patients with 98 treatments for lymph nodes (51), local recurrence (21), and de novo solid metastases (26). Median biologically effective dose (BED), gross tumor volume, and planning target volume were 38.40 Gy, 10.41 cc, and 25.21 cc, respectively. 52 lesions showed complete radiographic response, and two-year local control was 80%. Median overall survival (OS) was 35.2 months, and two-year progression-free survival (PFS) was 12%. On univariate analysis, Eastern Cooperative Oncology Group performance status > 0 was predictive of decreased OS (p = 0.0024) and PFS (p = 0.044). Factors predictive of local failure included lower BED (p = 0.016), treatment for recurrence (p = 0.029), and higher pre-treatment SUV (p = 0.026). Kaplan-Meier analysis showed BED ≤35 Gy (p < 0.005) and treatment for recurrence (p = 0.01) to be predictive of local failure. On Cox proportional hazards analysis, treatment of lymph nodes was predictive of complete radiographic response (hazard ratio (HR) = 4.95), as was higher BED (HR = 1.03). Toxicity included 27 cases of grade < 3 toxicity, and one grade 5 late toxicity of GI bleed from a radiation therapy-induced duodenal ulcer.ConclusionsSBRT provides durable local control with minimal toxicity in ovarian cancer, especially with BED > 35 Gy and treatment for lymph nodes.

Hormuth, David; Jarrett, Angela; Yankeelov, Thomas

2020 Radiation Oncology

doi: 10.1186/s13014-019-1446-2pmid: 31898514