Conventional Radiotherapy Group Research Articles

Efficacy and Safety of Radiotherapy Combined with Pyrotinib in the Treatment of HER2-Positive Breast Cancer with Brain Metastases.

To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM). This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR). The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B. For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.

Comparing Acute Oral Mucosa Toxicity Associated with Minibeam and Conventional Radiotherapy

Acute oral mucosa toxicity is associated with ulceration, severe pain, and nutritional deficiencies that may lead to treatment interruptions and a decreased quality of life for head and neck cancer patients. Minibeam radiotherapy (MRT) is a type of spatially fractionated radiotherapy that delivers an alternating pattern of sub-millimeter wide peaks of high dose immediately adjacent to much lower valley doses. By delivering a non-uniform dose distribution, MRT allows for elevated peak doses while maintaining extraordinary normal tissue tolerance. In this study, we used an acute oral mucosa toxicity mouse model to test the hypothesis that MRT provides superior tissue sparing compared to conventional radiotherapy (CRT). A total of 33 female C57BLJ6 mice were randomized by body weight (BW) across two CRT groups (n = 4/group) receiving open field radiation of 16 and 20 Gy and five MRT groups (n = 5/group) receiving peak:valley doses of 48:8, 72:12, 96:16, 96:8, and 152:8 Gy. All radiation was given in one fraction. The CRT groups were irradiated with a 10 mm circular field using a 225 kVp PA x-ray beam encompassing the oral cavity and oropharynx. The MRT groups were irradiated with the same arrangement, but the beam was collimated into 0.5 mm wide minibeams spaced 1.1 mm center-to-center using tungsten collimators of 0.5, 1, and 2.5 mm thickness to deliver peak-to-valley ratios (PVRs) of 6:1, 12:1, and 19:1. Acute effects in the oral mucosa were studied using changes in BW as a surrogate for clinically significant oral mucositis. BWs were measured daily starting on the day of treatment, and BW changes were computed relative to the day of treatment. The toxicity endpoint was defined such that mice losing >20% BW were humanely euthanized. Doses of 20 Gy CRT and 96:16 Gy MRT were highly toxic, with all animals in these groups reaching the toxicity endpoint between 9-11 days post-RT, compared to only one animal in the 16 Gy CRT group, and no animals in the other MRT groups. The BWs of all surviving animals returned to baseline within 15 days post-RT. The groups 48:8, 96:8, and 152:8 Gy showed similar BW loss and full recovery patterns. Additionally, the groups 48:8, 72:12, and 96:16 Gy showed that, for the same PVR, increasing the valley dose resulted in increased BW loss. Lastly, animals did not tolerate 96:16 Gy, but those in the 96:8 Gy group fully recovered. Despite the extreme toxicity caused by 20 Gy CRT, animals in the MRT groups tolerated peak doses up to 152 Gy when the valley dose was 8 Gy. These results confirm the superior normal tissue sparing capacity of MRT compared to CRT in an oral mucosa mouse model. We delivered tolerable MRT peak doses an order of magnitude larger than toxic CRT doses. Importantly, our results suggest that valley dose is the most useful parameter to assess acute toxicity when using MRT. Our data may prove useful for eventual clinical applications of MRT in head and neck cancers.

Dose Painting Radiotherapy Guided by Diffusion-Weighted Magnetic Resonance vs. 18F-FDG-PET/CT in Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled Clinical Trial

This phase II randomized controlled trial aimed at comparing the efficacy and toxicity of diffusion-weighted magnetic resonance imaging (DWI)-guided dose painting radiotherapy (DP-RT), FDG-PET/CT-guided DP-RT, and conventional MRI-based radiotherapy (RT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 330 patients with stage III-IVa NPC disease were randomly assigned in a 1:1:1 ratio to receive induction chemotherapy followed by concurrent chemoradiotherapy by DWI-guided DP-RT (group A, n = 110), FDG-PET/CT-guided DP-RT (group B, n = 110), or conventional MRI-based RT (group C, n = 110). All patients received volumetric modulated arc therapy (VMAT). In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). In group B, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx as the SUV50%max isocontour. The doses to GTVnx-DWI in group A and GTVnx-PET in group B were escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group C, planning gross tumor volume of nasopharynx (PGTVnx) was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR2200057476). Group A and B showed significant higher complete response (CR) rates than group C (100%, 100%, and 96.4% for group A, B and C, respectively, p = 0.036). In groups A, B and C, the 1-year local recurrence-free survival (LRFS) rates were 100%, 100%, and 94.5%, respectively (p = 0.002). The 1-year disease-free survival (DFS) rates were 100%, 99.1%, and 92.7%, respectively (p = 0.001). The 1-year distant metastasis-free survival (DMFS) rates were 100%, 99.1%, and 93.6%, respectively (p = 0.004). The 1-year overall survival (OS) rates were 100%, 100%, and 95.4%, respectively (p = 0.006). Group A and B had significantly higher 1-year LRFS, DFS, DMFS, and OS than those in group C. No significant differences were observed in LRFS, DFS, DMFS and OS between group A and B. Group B (PET/CT group) had a higher incidence of grade 3-4 acute ototoxicity (3.6%) than group A (0%) and group C (0%, p = 0.036). No significant differences in other grade 3-4 acute adverse events and late toxic effects were observed among the three groups, and no patient had grade 5 toxicities. Multivariate analysis showed that dose painting (DWI-guided DP-RT and PET/CT-guided DP-RT vs conventional MRI-based RT) was associated with improved LRFS, DFS, DMFS and OS. Both DWI-guided DP-RT and PET/CT-guided DP-RT plus chemotherapy are associated with improved LRFS, DFS, DMFS and OS compared with conventional MRI-based RT among patients with locoregionally advanced NPC. DWI-guided DP-RT does not increase toxicities, but PET/CT-guided DP-RT has higher incidence of acute ototoxicity.

The Effect of Dose-Fractionation Mode on the Immune Response and Therapeutic Effect of Lewis Lung Cancer Mice Model Based on Tumor Microenvironment

The therapeutic effect of different groups of Lewis lung cancer mice and the expression of immune cells in peripheral blood and tumor tissues of mice were observed after different dose-segmentation modes of treatment, so as to select the most suitable for stimulating immune effect with good prognosis and small side effects. Female homologous inbred C57BL/6 male mice at 6-8 weeks were selected and inoculated subcutaneously on the right thigh according to LLC: L929: lymphocyte = tumor cell suspension with PBMC(inactivated lymphocyte) = 5:1:1 ratio; after tumor growth to the size of 100-200mm3, different dose-segmentation modes were used for irradiation, which was divided into 5 groups, group A: no radiotherapy; Group B: 2Gy/qd, continuous radiotherapy for 30 days; Group C: 2Gy/bid, continuous radiotherapy for 13 days; Group D: 3Gy/bid, continuous radiotherapy for 10 days; Group E: 6Gy/qd, continuous radiotherapy for 8 days. On the 3rd day after radiotherapy, some mice were sacrificed, peripheral blood lymphocytes of mice were isolated with lymphocyte separation solution, and the transplanted tumor of mice was prepared into single-cell suspension. Then, the number of CD3+T cells, CD3+B cells, NK1.1 cells, CD3+CD4+T cells, CD3+CD8+T cells, CD4+Foxp3+Treg cells in peripheral blood and single-cell suspension of mice was detected by flow cytometry. HE staining was used to observe the tumor tissue structure of mice leg transplantation. The expressions of CD4, CD8, Foxp3 and CD31 in tumor tissues of each radiotherapy group were observed by immunohistochemical staining (IHC) in paraffin sections. The survival time of mice in group C (2Gy/ bidx13d) was significantly improved compared with that in group B (2Gy/qdx30d), and the twin-daily segmentation mode could improve the elevation of Treg cells after once-daily segmentation mode radiotherapy in both peripheral blood and tumor tissues. There was no significant difference in the survival time of mice in group E (6Gy/qdx8d) and group D (3Gy/bidx10d), the number of Treg cells in peripheral blood of mice in group E was significantly lower than that in group D, but there were more Treg cells in tumor tissue of mice in group E than group D. Compared with the control mice, the overall immunity of the experimental group was inhibited. The twice-daily segmentation mode in the conventional dose radiotherapy group significantly improved Treg in peripheral blood and tumor immune microenvironment and promoted neovascularization. The twice-daily segmentation mode in the high-dose radiotherapy group improved the immunosuppression of lymphocytes in peripheral blood but increased immunosuppression in tumor microenvironment.

Compare the impact of simultaneous integrated boost radiotherapy and conventional radiotherapy with sequential boost to early breast cancer patients

PurposeIn this study, we aimed to evaluate the toxicity and the irradiated volume of the organs at risk (OAR) of two radiotherapy (RT) techniques for breast cancer patients after breast conservative surgery (BCS) for 10 years. Methods140 patients with early breast cancer (T0∼2N0∼1M0, stage Ⅰ∼Ⅱ) participated in this study. Half of the patients received simultaneous integrated boost (SIB) and other half received conventional radiotherapy (CRT). We compared the toxic effects on cosmetic outcome (CO), volume to the OAR and recurrence-free period (RFP) between SIB and CRT. ResultsThe incidence of acute grade 1 skin toxicity (χ2 = 8.400, p = 0.040) and chronic skin reactions (χ2 = 11.020, p = 0.001) were significantly different between the two RT techniques (p < 0.05). All patients were satisfied with the CO (χ2 = 0.714, p = 0.398). There was no serious organ damage during the process of radiotherapy. There was less volume leakage to the lungs with 20Gy volume (p < 0.05). No significant difference in the volume to the lungs at 1000 cGy and heart at 1000/3000 cGy was observed between SIB and CRT (p ≥ 0.05). Patients in the SIB group were hospitalised and treated for a significantly shorter period of time than those in the CRT group (p < 0.05). All patients were alive at the last follow-up. There were no significant differences in RFP between the two techniques (p ≥ 0.05). ConclusionCompared with patients in the CRT group, the SIB group has a shorter treatment duration without increased toxicity, with advantages in terms of dose-limiting capacity and cosmetic results of treatment. The recurrence-free rate in the SIB group is satisfactory and is a recommended treatment.

Chronotherapy in head and neck cancer (HNC): A systematic review.

e18016 Background: Chronotherapy in cancer is optimizing the administration time of anti-cancer treatment according to circadian rhythm and cellular phase to improve the efficacy against tumor cells while decreasing side effects on normal cells. Several randomized controlled trials (RCT) evaluated chronotherapy of chemotherapy (chrono-chemotherapy: time-specific infusions) and/or radiotherapy (chrono-radiotherapy: morning radiotherapy) in various cancers and reported improved treatment efficacy and reduced toxicity. However, the effect of chronotherapy in HNC treatment is unclear as there are no prior systematic reviews reported. Therefore, this systematic review summarizes available clinical evidence on the effect of chrono-chemotherapy (CCT) and chrono-radiotherapy (CRT) on treatment response and adverse events in HNC adult patients. Methods: We conducted a systematic search using Medical Subject Headings (MeSH) in four online databases (OVID, Embase, CINAHL and Scopus), and 6078 articles identified were published in English between the databases' inception date and June 30, 2022. We included original peer-reviewed retrospective and prospective human studies investigating CCT and/or CRT versus conventional treatments in HNC patients. We excluded articles that contained no abstract, were unrelated to HNC, were pre-clinical and case reports, or did not include time-specific interventions in their methods. Results: 16 studies were finally included. Overall, studies were heterogenous in demographics, study design, intervention, and outcome measures, thus meta-analysis could not be performed. Nine studies (RCT = 3, Non-RCT = 2 &amp; Retro = 4) investigated CRT. Squamous cell carcinoma (SCC) was mainly reported as the primary tumor (stage I-II). 7/9 studies reported a significant reduction in the incidence of oral mucositis (Grade ≥3) in the CRT group as opposed to conventional radiotherapy (RT) groups (p &lt; 0.05). In contrast, treatment response was investigated in 4/9 studies and was insignificant (p &gt; 0.05). Seven studies (RCT = 5 &amp; Retro = 2) investigated CCT in patients diagnosed with SSC (stage II-IV). All included studies had concurrent RT. Different chemotherapeutic agents were used in combinations or as a single agent, namely Cisplatin, 5- Fu, Paclitaxel and Docetaxel. CCT groups in all studies achieved a significant reduction in Nausea &amp; Vomiting (Grade ≥3), while a significant reduction in Leukopenia &amp; Thrombocytopenia (Grade ≥3) was reported in 2 studies only (p &lt; 0.05). Treatment response (OS and PFS) was not significantly different (p &gt; 0.05) between both groups except 2 studies reported significantly higher ORR in chronotherapy groups (p &lt; 0.05). Conclusions: CCT and CRT in HNC treatment in most studies provided evidence of toxicity reduction while treatment response was maintained. However, large multicentric randomized controlled studies with standardized protocols and optimized designs are still needed.

Clinical study of interstitial brachytherapy for 72 cases of recurrent cervical cancer.

To determine the application value of interstitial brachytherapy in the treatment of recurrent cervical cancer. A retrospective analysis was conducted on the clinical data of 72 patients with recurrent cervical cancer admitted to The Fourth Hospital of Hebei Medical University from September 2017 to April 2022. They were divided into two groups according to different brachytherapy methods: conventional after-load radiotherapy group and interstitial brachytherapy group. After treatment, regular outpatient reviews or telephone follow-ups were conducted to evaluate the efficacy, related toxic and side effects and prognostic factors. The short-term efficacy of the interstitial brachytherapy group was significantly higher than that of the interstitial brachytherapy group (p<0.05). The one-year LC and two-year LC of the interstitial brachytherapy group were 94% and 90.6%, respectively, while those of the conventional after-load group were 74.5% and 67.8%, respectively, with a statistically significant difference (p<0.05). The clinical efficacy of peripheral recurrence was 13.9% in the interstitial brachytherapy group, and that in the conventional after-load group was 2.7%, with a statistically significant difference (p<0.05). There was a statistically significant difference in late toxic and side effects between the two groups (p<0.05). Prognostic factors: Multivariate analysis of the COX regression model showed that only the maximum tumor diameter was an independent prognostic factor for OS and PFS, while the recurrence site and brachytherapy method were the independent prognostic factors for LC. Interstitial brachytherapy radiotherapy touts various benefits in the treatment of patients with recurrent cervical cancer, such as good short-term efficacy, high local control rate, reduced incidence of advanced bladder and rectal toxicity, and improved quality of life.

Dose-escalated radiotherapy for clinically localized and locally advanced prostate cancer.

Dose-escalated radiotherapy for clinically localized and locally advanced prostate cancer.

High-dose proton beam therapy versus conventional fractionated radiation therapy for newly diagnosed glioblastoma: a propensity score matching analysis

BackgroundHigh-dose proton beam therapy (PBT) uses excellent dose concentricity based on the unique characteristic termed the Bragg peak. PBT is a highly feasible treatment option that improves survival in select patients with newly diagnosed glioblastoma (GBM). However, selection bias remains an issue in prior studies that evaluated the efficacy of PBT. The aim of the present study was to compare the survival outcomes and toxicities of high-dose PBT and conventional radiation therapy (CRT) using propensity score-matched treatment cohorts.MethodsThe analysis included patients with newly diagnosed GBM treated with high-dose PBT of 96.6 Gy (RBE) or CRT of 60 Gy from 2010 to 2020. Propensity score generation and 1:1 matching of patients were performed based on the following covariates: age, sex, tumor location, extent of resection, chemotherapy, immunotherapy, and pre-radiation Karnofsky performance scale score.ResultsFrom a total of 235 patients, 26 were selected in each group by propensity score matching. The median overall survival (OS) of the PBT group was 28.3 months, while the median OS of the CRT group was 21.2 months. Although acute radiation-related toxicities were equivalent between the PBT and CRT groups, radiation necrosis as a late radiation-related toxicity was observed significantly more frequently in the PBT group.ConclusionsHigh-dose PBT provided significant survival benefits for patients with newly diagnosed GBM compared to CRT as shown by propensity score matching analysis. Radiation necrosis remains an issue in high-dose PBT; thus, the establishment of an effective treatment strategy centered on bevacizumab would be essential.

Outcomes of Different Radiation Therapy Dose-splitting regimens after Radical Surgery for Early stage Breast Cancer

Objective: To investigate the outcomes of different dose-splitting radiotherapy regimens after radical or modified radical surgery for early-stage breast cancer. Material and methods: Between 2015 and 2020, 412 patients treated with radiotherapy after radical or modified radical surgery for early-stage breast cancer were allocated into 3 groups according to different dose-splitting regimens of postoperative radiotherapy. Conventional radiotherapy group157 cases, 2Gy/ fraction, once/day, 5 times/week, DT50 Gy; Alternate-day radiotherapy group 202 cases, 3 Gy/fraction, 3 times/week, DT45Gy; Fast radiotherapy group 53 cases, Days 1 and 3, 5Gy/fraction, Days 15 and 17, 6.5 Gy/fr, DT23Gy. Overall, 318 cases were treated with chemotherapy and/or hormone therapy. For the whole group, the 5-year overall and disease-free survival rates were 87.4% and 89.6% respectively. The 5-year disease-free survival rates for the Conventional radiotherapy group, the Alternate-day radiotherapy group, and the Fast radiotherapy group were 90.8%, 86.5%, and 84.6% (P=0.13).The locoregional recurrence rates were 7.0%, 9.9 and 5.7 respectively. There was no significant difference between the three groups in terms of local control. Conclusion: With similar 5-year disease-free-survival rates, and the same efficacy, Alternate-day radiotherapy has the advantage of giving fewer fractions, which is suitable for a unit with limited resources. Fast radiotherapy shortens the duration of the treatment, and its efficacy and toxic effects deserve further study.

Hypofractionated Radiotherapy for Early-Stage Breast Cancer: A Propensity Score Matched Analysis.

BackgroundIn patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost.MethodsWe retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR). DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test.ResultsTotal 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated. The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%).ConclusionHypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Outcomes of Image-Guided Moderately Hypofractionated Radiotherapy for Stage III Non-Small-Cell Lung Cancer.

Objective To evaluate the efficacy and toxicity of hypofractionated radiotherapy (hypo-RT) for stage III non-small-cell lung cancer (NSCLC) in the Chinese population. Methods Eighty-six stage III NSCLC patients who received hypo-RT (60 Gy/20 fractions, BED = 78.00 Gy: 73 patients; 62.5 Gy/25 fractions, BED = 78.13 Gy: 13 patients) were recruited. Fifty-seven patients who received conventional radiotherapy (60 Gy/30 fractions, BED = 72.00 Gy) during the same period were enrolled as the control group. All hypo-RT treatments were conducted using image-guided technology. The efficacy and toxicity of the treatment were compared between the two groups. Results The median duration of follow-up was 23.0 months (range: 4.0–82.0 months). Univariate and multivariate analyses of all 143 stage III NSCLC patients revealed that hypo-RT was an independent factor for progression-free survival (PFS) and overall survival (OS). The median PFS and OS of hypo-RT were significantly higher than in the conventional RT group (PFS: 14.30, 11.00 months, p=0.035; OS: 43.30, 31.50 months, p=0.045). The incidence rates of symptomatic radiation pneumonitis and radiation esophagitis (≥grade 2) were 17.77% and 27.91%, respectively, in the hypo-RT group. Compared to the conventional radiation therapy group (22.81% and 19.30%, respectively), no significant differences were found between the two common side effects (p=0.662 and p=0.241, respectively). Conclusion For Chinese stage III NSCLC patients, image-guided hypo-RT offers favorable prognosis, and the treatment toxicity was totally acceptable. This radiation modality deserves further prospective clinical trials.

PO-1110 Local control in hypofractionated RT after breast-conservative surgery among young Egyptian patients

Purpose or Objective Since the beginning of coronavirus disease (COVID-19), there is a compelling reason for the use of hypofractionated radiotherapy (HFRT) schedules in cancer management to safeguard the patients and the treating physicians. However, conflicting data shows that young breast cancer (BC) patients have a higher locoregional relapse after breast-conservative surgery (BCS). Given this, we aim to compare the locoregional control between conventional radiotherapy (CRT) and HFRT after BCS in a cohort of young BC patients. Materials and Methods We retrospectively reviewed stage I-III BC patients in two centers diagnosed between 2008 and 2017 who underwent BCS and had follow-up data. Patients were categorized into two groups: CRT (50Gy in 25 fractions) vs. HFRT (40.5 - 42.5 Gy in 15-16 fractions). Boost was added to all patients. Results 247 patients were included in this analysis. Among them, 87 (35%) received CRT, while 160 (65%) were treated by HFRT. The clinicopathological characteristics of CRT vs. HFRT were as follows: The majority of the patients were T1 and T2, 92% in CRT vs. 94% in HFRT. N3 was rare in both groups, 8.3% vs. 5.1% in CRT vs. HFRT, respectively. The CRT had more stage 3 patients than HFRT, 35% vs. 23% respectively, but fewer stage 1 (18.1 vs. 23.5%, respectively). Estrogen/progesterone receptor (ER/PR) positive was 79.5% vs. 76.7%, HER2 enriched was 7% vs. 5%, while high Ki-67 was 56.3% vs. 71.4% in CRT vs. HFRT, respectively. Lymphovascular invasion was positive in 52.7% of CRT vs. 64.3% in HFRT, while the extracapsular extension was positive in 31% of CRT vs. 19.4% in HFRT. The distribution of tumor grades was similar across the groups. After a median follow up of 42 months (range: 5-135), 10% of the total 247 patients developed locoregional recurrences:13.8% (n=12) were in CRT group, whereas 8.1% (n=13) in HFRT, p = 0.158;the HFRT group had insignificant lower locoregional recurrences. In univariate and multivariate analysis, only very young age was an independent poor prognostic factor for locoregional failure. Conclusion We found no significant differences in locoregional control between CRT and the HFRT following BCS among young BC patients. In this COVID-19 pandemic, HFRT should also be considered in young BC patients to shorten the treatment time.

Hypofractionated Radiotherapy Using Simultaneous Integrated Boost Technique with Concurrent and Adjuvant Temozolomide for Glioblastoma

Aim: This study was conducted to assess the safety and efficacy of postoperative hypofractionated radiotherapy (HRT) using simultaneous integrated boost (SIB) technique for glioblastoma (GBM) compared to conventional radiotherapy (CRT).&#x0D; Study Design: This was a prospective study with historical control arm.&#x0D; Place and Duration of the Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019.&#x0D; Methods: The intervention (HRT) group included 30 patients who received 3D conformal HRT with SIB using field in field (FIF) technique to deliver a differential radiation dose to different targets. Planning target volume 60 (PTV60) includes the gross target volume (GTV) plus a 5-mm margin, and PTV45 includes the GTV plus a 15-mm margin. PTV60 will receive 60 Gy in 20 fractions, and PTV45 will receive 45 Gy in the same 20 fractions (one fraction daily and 5 days per week).The CRT group included 30 patients who received 3D conformal CRT with total dose 60 Gy in 2-Gy fractions delivered over 6 weeks. Both groups was planned to receive concurrent and adjuvant temozolamide.&#x0D; Results: The median PFS was 10 months in both groups. The median OS was 13 months in HRT group versus 12 months in CRT group which is statistically non significant. The toxicities were mild and acceptable. Performance status and adjuvant temozolamide were significant predictors that affect the overall survival.&#x0D; Conclusions: HRT with SIB using 3D conformal RTH with (FIF) technique in patients with GBM is a feasible and safe treatment and its results is comparable to the conventional radiotherapy.

DIPG-28. REPEATED LOW DOSE RT FOR PEDIATRIC DIPG – LESS DISEASE BURDEN WITH COMPARABLE OUTCOMES

PURPOSEPediatric diffuse intrinsic pontine glioma (DIPG) is the most dismal prognosis pediatric brain tumor. Six weeks radiation therapy (RT) remains the mainstay of treatment. The aim of the current study was to compare the results of firstly reported repeated low dose RT (rLRT) with conventional RT (CRT). METHODS AND MATERIALS: This retrospective review included 24 children with DIPG, aged 3 -18 years, underwent CRT (52- 60.0 Gy in 1.8- 2.0 Gy, n = 16) or rLRT (18 - 30 Gy in 1.5–2.0 Gy per cycle for 1–3 cycles, n = 8). All children had typical symptoms and MRI features of DIPG, or biopsy-proven DIPG.RESULTSThe median overall survival (OS) was 12.6 months in rLRT group and 11.4 months in CRT group (p =0.347), progression-free survival (PFS) was 3.6 months in rLRT group and 6.5 months in CRT group (p = 0.821), no significant survival difference was observed between two groups. Temporary discontinuation or tapering of steroids rate was significantly higher in rLRT group (100% vs 60%, p = 0.028). Although not statistically significant, mean non-hospitalized days were longer in the rLRT group, 403 days versus 305 days in the CRT group, as were mean cumulative progression-free days, 276 days versus 163 days and 1-year free from CSF diversion rate was higher, 100% versus 64.9%.CONCLUSIONSFor patients with newly diagnosed DIPG, repeated low dose RT, given over 3 to 4 weeks per cycle for 1 to 3 cycles, offers comparable survival outcome with less disease burden compared with conventional RT.

Hypofractionated Radiotherapy in Combination With Chemotherapy Improves Outcome of Patients With Esophageal Carcinoma Tracheoesophageal Groove Lymph Node Metastasis.

This study investigated the efficiency and safety of hypofractionated radiotherapy (HFR) combined with paclitaxel chemotherapy for the treatment of postsurgery tracheoesophageal groove lymph node (TGLN) metastasis in patients with esophageal cancer (EC). Fifty-three EC patients with TGLN metastasis after surgery admitted to the Yancheng Third People’s Hospital from January 2013 to June 2015 were included in this study. They were randomly divided into the HFR group (n = 25) and conventional fractioned radiotherapy (CFR) group (n = 28) based on the random grouping method. Patients in the HFR group received treatment with radiation of 60 Gy (5 fractions per week, total 20 fractions) combined with paclitaxel chemotherapy at a dose of 50 mg once per week for 4 weeks. Patients in the CFR group received radiation of 60 Gy (5 fractions per week, total 30 fractions) combined with paclitaxel chemotherapy at a dose of 50 mg once per week for 6 weeks. The adverse events and treatment outcomes in these two groups were analyzed. It was found that there was no significant difference in the incidence of radiation esophagitis in the HFR group compared with that of the CFR group (grades 3–4, 44.0 vs. 25.0%; P = 0.149). There was no statistical difference in the incidence of radiation pneumonitis between these two groups (grades 3–4, 16.0 vs. 7.1%; P = 0.314). No statistical difference was noticed in complete response (CR), partial response (PR), and no response (NR) between these two groups. The median overall survival (OS) in the HRF group was significantly longer compared with that of the CRF group (24.2 months (95% CI, 16.2–32.1 months) vs. 11.8 months (95% CI, 9.2–14.4 months); P = 0.024). Our results indicated that the combination of HFR and chemotherapy improved the prognosis of EC patients with TGLN metastasis with no increased adverse events.

Utilization of Hypofractionated Whole-Breast Radiotherapy With Concurrent Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Therapy

IntroductionHypofractionated radiotherapy (Hypo-RT) is now considered the standard of care for the majority of patients receiving whole-breast irradiation (WBI). However, there are few data on the use of Hypo-RT in human epidermal growth factor receptor 2 (HER2)-positive patients receiving concurrent anti-HER2 therapy. In this study, we sought to examine patterns of WBI in HER2-positive patients. Patients and MethodsUsing the National Cancer Data Base, we identified women with nonmetastatic HER2-positive breast cancer diagnosed between 2010 and 2015 who received WBI. The Hypo-RT group was defined as those receiving 21 or fewer fractions. All other patients were in the conventional radiotherapy (RT) group. Multivariate logistic regression was used to identify predictors of Hypo-RT utilization. Five-year overall survival was estimated by the Kaplan-Meier method. ResultsThe study included 15,776 patients, of whom 17.7% received Hypo-RT. The rate of Hypo-RT utilization increased from 7.4% in 2010 to 29.3% in 2015 (P = .004). Predictors of Hypo-RT use included older age (≥60 vs. < 60 years), higher median income quartile, further distance from the treatment facility (>50 vs. ≤50 miles), treatment at an academic facility, and later year of diagnosis. Unadjusted 5-year overall survival rates were similar among patients who received Hypo-RT and conventional RT (93.9% vs. 95.2%, P = .26). After adjusting for patient, facility, and tumor variables, Hypo-RT was not significantly associated with survival. ConclusionAlthough Hypo-RT was not commonly delivered in patients with HER2-positive breast cancer, the utilization rate quadrupled over the study period. Multiple socioeconomic and clinical predictors of Hypo-RT receipt were identified. Adjuvant RT regimen was not significantly associated with overall survival.

Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters

To evaluate the effect and mechanism of radiotherapy (RT)–sorafenib pharmacokinetics (PK) in different regimens with conventional or high dose irradiation. Between February 2012 and December 2018, 43 patients with portal vein tumor thrombosis treated with sorafenib plus conventional RT (58%) or stereotactic body radiation therapy (SBRT, 42%) were retrospectively reviewed. In vivo and in vitro studies of concurrent and sequential RT with sorafenib were designed. SBRT resulted in a 3-fold increase in complete recanalization compared to conventional RT group (28% vs. 8%, p = 0.014). Compared to the control group, the area under the concentration vs. time curve (AUC) of sorafenib was increased in the concurrent RT2Gy and RT9Gy groups and the sequential RT9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential RT2Gy group (p = 0.036). Sequential RT2Gy and RT9Gy increased CYP3A4 activity by 82% (p = 0.028) and 203% (p = 0.0004), respectively, compared to that with the corresponding concurrent regimen. SBRT produced better recanalization than conventional RT with sorafenib. The AUC of sorafenib was modulated by RT. P-gp expression was not influenced by RT. The sequential RT regimen increased CYP3A4 activity that may increase the RT-sorafenib synergy effect and overall sorafenib activity. The biodistribution of sorafenib was modulated by local RT with the different regimens.

Hypo-fractionation radiotherapy normalizes tumor vasculature in non-small cell lung cancer xenografts through the p-STAT3/HIF-1 alpha signaling pathway.

Background:Hypo-fractionation radiotherapy (HFRT) was considered to be an important treatment for non-small cell lung cancer (NSCLC), but the radiobiological effects of HFRT on NSCLC remain unclear. The aim of this study was to investigate specific biological effect of HFRT on tumor angiogenesis, compared with conventional radiotherapy (CRT).Methods:The subcutaneous xenograft models and the dorsal skinfold window chamber (DSWC) models of nude mice bearing H460 and HCC827 NSCLC cells were irradiated with doses of 0 Gy (sham group), 22 Gy delivered into 11 fractions (CRT group) or 12 Gy delivered into 1 fraction (HFRT group). At certain time-points after irradiation, the volumes, hypoxic area, coverage rate of pericyte and micro-vessel density (MVD) of the subcutaneous xenograft models were detected, and the tumor vasculature was visualized in the DSMC model. The expressions of phosphorylated signal transducer and activator of transcription (p-STAT3), hypoxia-inducible factor 1-α (HIF-1α), CXCL12 and VEGFA were detected.Results:Compared with the CRT groups, HFRT showed more-efficient tumor growth-suppression, accompanied by a HFRT-induced window-period, during which vasculature was normalized, tumor hypoxia was improved and MVD was decreased. Moreover, during the window-period, the signal levels of p-STAT3/HIF-1α pathway and the expressions of its downstream angiogenic factors (VEGFA and CXCL12) were inhibited by HFRT.Conclusion:Compared with CRT, HFRT induced tumor vasculature normalization by rendering the remaining vessels less tortuous and increasing pericyte coverage of tumor blood vessels, thereby ameliorating tumor hypoxia and enhancing the tumor-killing effect. Moreover, HFRT might exert the aforementioned effects through p-STAT3/HIF-1α signaling pathway.

Short term outcomes of helical tomotherapy during concurrent chemoradiotherapy for advanced cervical cancer.

The aim of the present study was to clarify the feasibility and efficacy of helical tomotherapy during concurrent chemoradiotherapy for treating cervical cancer. The medical records of 13 patients who underwent oncurrent chemoradiotherapy using helical tomotherapy for cervical cancer at Wakayama Medical University Hospital between 2013 and 2015 were retrospectively reviewed. A total of 15 patients who underwent oncurrent chemoradiotherapy using conventional radiotherapy (CRT) between 2008 and 2013 at our institution were also examined for comparison. The median age of patients treated with helical tomotherapy was 60 (range, 35-71), and the median age of patients treated with CRT was 57 (range, 43-77). The median follow-up period was 27 months (range, 3-46) in the tomotherapy group and 35 months (range, 7-88) in the CRT group. The frequency of G3/4 thrombocytopenia in the tomotherapy group was significantly higher than that in the CRT group (P=0.049). However, the platelet count spontaneously recovered without transfusion. There were no significant differences between the groups in terms of frequency of G3/4 neutropenia, diarrhea or late intestine injury. The rate of complete response in the tomotherapy group and the CRT group was 84.6 and 73.3%, respectively, and there was no significant difference in the response rate between the groups. There were no significant differences in the progression-free survival or progression-free rate in the irradiation field between the groups. Adverse events from concurrent chemoradiotherapy using helical tomotherapy were acceptable and clinically controllable. The present results suggest that helical tomotherapy is efficient during concurrent chemoradiotherapy for treatment of advanced cervical cancer.