Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used and their comparative efficacy and safety remain unclear. METHODS: Patients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in our study. Three different nCRT regimens were retrospectively compared: Conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the CROSS trial (CROSS). The overall survival (OS), pathological complete response (pCR) rates, toxicities, and treatment compliance were analyzed. RESULTS: Among the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. OS at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (p < 0.001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (p = 0.653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and non-hematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, 5.5% and 0.8% in Conv-FP, Hypo-FP, and CROSS, respectively (p = 0.002 and 0.030). Weight loss > 5% was observed in 44.0%, 51.4%, and 32.5%, respectively (p < 0.001). In the multivariate analysis, clinical T-stage (p = 0.004), N-stage (p = 0.012), the use of FP chemotherapy regimen (p = 0.013), surgical resection (p < 0.001), hematologic toxicity (p = 0.001), and weight loss (p = 0.004) were significantly associated with poor OS. CONCLUSION: The choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting it may be the optimal treatment option among the groups. SYNOPSIS: This study compared three different neoadjuvant chemoradiotherapy (nCRT) regimens for locally advanced esophageal squamous cell cancer (LA-ESCC): Conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP), hypofractionated RT + FP, and regimens from the CROSS trial. The overall survival (OS), pathological complete response (pCR) rates, toxicities, and treatment compliance were analyzed. Results showed that the choice of nCRT regimen did not significantly affect pCR rates, but the CROSS regimen showed better OS and lower toxicity, suggesting it may be the optimal treatment option. DATA AVAILABILITY: Data availability is limited due to institutional data protection law and confidentiality of patient data.

Reduced frequency and severity of radiation esophagitis without marginal failure risk by contralateral esophagus sparing IMRT in stage III non-small cell lung cancer patients undergoing definitive concurrent chemoradiotherapy.

PURPOSE: Radiation esophagitis is frequent and annoying toxicity in high dose thoracic radiation therapy. Contalateral esophagus sparing intensity modulated radiation therapy (CES-IMRT) has been proposed to mitigate this problem, and this is to report the impact of CES-IMRT in definitive concurrent chemoradiotherapy (dCCRT) for lung cancer patients. MATERIALS AND METHODS: From January 2021 till May 2023, 183 stage III non-small cell lung cancer patients underwent dCCRT. Esophagus was located within 1 cm from internal target volume in 159 patients. We comparatively evaluated the frequency and severity of esophagitis by pain-killer usage, analgesic quantification algorithm (AQA) score, and failure patterns in 159 CES-necessary patients. RESULTS: All patients underwent dCCRT (66 Gy in 30 fractions with concurrent chemotherapy). Actual CES-IMRT application was determined based on the discretion of responsible radiation oncologists: CES-applied in 41 patients; and CES-unapplied in 118. CES-applied patients experienced pain events less frequently (pain-killer usage: 53.7 % vs. 77.1 %, p = 0.008) and less severely (AQA score of 2-3: 39.0 % vs. 68.6 %, p = 0.002). On multivariate analyses, overlapping volume of esophagus and planning target (HR = 1.32, 95 % CI 1.12-1.55, p = 0.001) and CES-IMRT application (HR = 0.31, 95 % CI 0.13-0.76, p = 0.010) were associated with AQA score of 2-3 less frequently. There were no differences in failure pattern, progression-free survival, and overall survival. CONCLUSIONS: CES-IMRT application resulted in less frequent and less severe pain events without compromising oncologic outcomes. Further studies, preferably in a randomized fashion, would be desired.

Dose-Escalated Radiotherapy for Primary Tracheobronchial Adenoid Cystic Carcinoma.

Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim.

Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma.

BACKGROUND: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. METHODS: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. RESULTS: The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. CONCLUSION: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.

Clinical Outcomes in Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinus: A Comparative Analysis of Treatment Modalities.

This study aimed to present the treatment patterns and outcomes for adenoid cystic carcinoma (ACC) arising in the nasal cavity and paranasal sinus. Sixty-one sinonasal ACC patients were retrospectively reviewed: 31 (50.8%) underwent surgery followed by postoperative radiation therapy (S+PORT), and 30 (49.2%) received definitive radiation therapy (D(C)RT). T4 disease was significantly more frequent in the D(C)RT group (25.8% vs. 80.0%, p < 0.001), where all T4b disease patients underwent D(C)RT. The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival were 61.8% versus 37.8% (p = 0.003), 64.8% versus 38.1% (p = 0.036), 52.6% versus 19.3% (p = 0.010), and 93.2% versus 73.4% (p = 0.001) in the S+PORT and D(C)RT groups, respectively. The absolute differences in 5-year rates of LFFS, DMFS, and PFS between the two groups were smaller in the T3-4 subgroup. The univariate analysis showed that T4b disease, neurologic symptoms, longest diameter of tumor, radiological evidence of nerve involvement, and undergoing D(C)RT were associated with worse clinical outcomes, but the significance disappeared in the multivariate analysis, except for in the case of radiological evidence of nerve involvement. In conclusion, most patients with extensive disease underwent upfront D(C)RT and generally exhibited inferior clinical outcomes when compared to those with less extensive disease and who underwent S+PORT.

Comparison of radiotherapy techniques in patients with thymic epithelial tumor who underwent postoperative radiotherapy.

PURPOSE: This retrospective study aimed to compare clinical outcomes and dosimetric parameters between radiation therapy (RT) techniques in patients with thymic epithelial tumor (TET). MATERIALS AND METHODS: From January 2016 to December 2020, 101 patients with TET received adjuvant RT (median, 52.8 Gy; range, 48.4 to 66.0). Three different RT techniques were compared: three-dimensional conformal RT (3D-CRT; n = 59, 58.4%), intensity-modulated RT (IMRT; n = 23, 22.8%), and proton beam therapy (PBT; n = 19, 18.8%). RESULTS: The median age of the patients and the follow-up period were 55 years (range, 28 to 79) and 43.4 months (range, 7.7 to 77.2). Patients in the PBT group were of the youngest age (mean age, 45.4 years), while those in IMRT group had the largest clinical target volume (mean volume, 149.6 mL). Patients in the PBT group had a lower mean lung dose (4.4 Gy vs. 7.6 Gy vs. 10.9 Gy, respectively; p < 0.001), lower mean heart dose (5.4 Gy vs. 10.0 Gy vs. 13.1 Gy, respectively; p = 0.003), and lower mean esophageal dose than patients in the 3D-CRT and IMRT groups (6.3 Gy vs. 9.8 Gy vs. 13.5 Gy, respectively; p = 0.011). Twenty patients (19.8%) showed disease recurrence, and seven patients (6.9%) died. The differences in the survival rates between RT groups were not statistically significant. CONCLUSION: In patients with TET who underwent adjuvant RT, PBT resulted in a lower dose of exposure to adjacent organs at risk. Survival outcomes for patients in PBT group were not significantly different from those in other groups.

Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer.

Purpose: To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection. Methods: Data from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity. Results: The median follow-up was 28.9 months (range, 1.1-62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months' post-PBT (p=0.047) and was maintained until 13 months (p=0.028). Conclusion: Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.

Recent trends in radiotherapy use for major cancers in Korea.

BACKGROUND: Although the trend in radiotherapy in all cancer patients has been studied, changes in radiotherapy modalities for specific cancer types have not been reported. This study aimed to analyze radiotherapy patterns for major cancers in Korea in recent years. MATERIALS AND METHODS: We collected data from claims and reimbursement records of the Health and Insurance Review and Assessment Service from 2017 to 2020, according to initial diagnostic codes. The radiotherapy modalities for major cancers, such as lung, stomach, colorectal, breast and liver cancer, were analyzed. The radiotherapy modalities consisted of two-dimensional radiotherapy, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, proton radiotherapy and stereotactic body radiotherapy. RESULTS: Overall, from 2017 to 2020, the use of two-dimensional radiotherapy and three-dimensional conformal radiotherapy decreased, and intensity-modulated radiotherapy increased. In 2017, three-dimensional conformal radiotherapy accounted for approximately half of the radiotherapy in patients for lung and colorectal cancer, which was replaced by intensity-modulated radiotherapy in 2020. In 2020, stereotactic body radiotherapy also accounted for a large proportion of radiotherapy used in liver cancer cases. Intensity-modulated radiotherapy was most used, followed by three-dimensional conformal radiotherapy and two-dimensional radiotherapy for breast cancer in 2020. Among major cancers, radiotherapy utilization for breast cancer is the highest. Compared with other cancers, the number of patients receiving radiotherapy for stomach cancer was low. CONCLUSION: The number of patients receiving radiotherapy for major cancers has increased. The use of advanced forms of radiotherapy, such as intensity-modulated radiotherapy, is rapidly increasing for major cancers. The rate of radiotherapy utilization was higher in major cancer patients than in all cancer patients.

Sublobar Resection versus Stereotactic Body Radiation Therapy for Clinical Stage I Non-Small Cell Lung Cancer: A Study Using Data from the Korean Nationwide Lung Cancer Registry.

PURPOSE: Stereotactic body radiotherapy (SBRT) had been increasingly recognized as a favorable alternative to surgical resection in patients with high risk for surgery. This study compared survival outcomes between sublobar resection (SLR) and SBRT for clinical stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Data were obtained from the Korean Association of Lung Cancer Registry, a sampled nationwide database. This study retrospectively reviewed 382 patients with clinical stage I NSCLC who underwent curative SLR or SBRT from 2014 to 2016. RESULTS: Of the patients, 43 and 339 underwent SBRT and SLR, respectively. Patients in the SBRT group were older and had worse pulmonary function. The 3-year overall survival (OS) rate was significantly better in the SLR group compared with the SBRT group (86.6% vs. 57%, log-rank p < 0.001). However, after adjusting for age, sex, tumor size, pulmonary function, histology, smoking history, and adjuvant therapy, treatment modality was not an independent prognostic factor for survival (hazard ratio, 0.99; 95% confidence interval, 0.43 to 2.77; p=0.974). We performed subgroup analysis in the following high-risk populations: patients who were older than 75 years; patients who were older than 70 years and had diffusing capacity of lung for carbon monoxide ≤ 80%. In each subgroup, there were no differences in OS and recurrence-free survival between patients who underwent SLR and those who received SBRT. CONCLUSION: In our study, there were no significant differences in terms of survival or recurrence between SBRT and SLR in medically compromised stage I NSCLC patients. Our findings suggest that SBRT could be considered as a potential treatment option for selected patients.

Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells.

Background: We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT). Materials and methods: After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs. Results: The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT. Conclusion: The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.

Recent Trends of Medical Expenses Associated with Radiation Therapy in Korea Based on HIRA Big Data.

PURPOSE: We aimed to determine the trends in the use of radiotherapy (RT) and the expenses associated with it in South Korea. Materials and Methods: The statistical data of the claims and reimbursement records provided on the Health and Insurance Review and Assessment Service website were utilized. This included information such as the number of patients, fractions, medical expenses according to treatment codes, in/outpatient, sex, age, and regions of hospitals. We analyzed data from 2016 to 2020. RESULTS: With a growing RT infrastructure and an increase in the number of radiation oncologists, the expenses for RT were 605.5 million USD in 2020, which had increased 1.5 times from 394.7 million USD in 2016. This growth was mainly because of the increased usage of advanced RT techniques. Furthermore, the proportion of intensity-modulated radiation therapy (IMRT) expenses in the total expenses increased by 1.6 times from 48.8% in 2016 to 76.9% in 2020. Advanced techniques were used more commonly in older individuals or children. However, the proportion of IMRT expenses increased mostly in young women. Additionally, geographical differences in RT use and expense were observed, although the gap in the IMRT fractions decreased among the regions. CONCLUSION: Recent medical expenses associated with RT in Korea have increased in tandem with technological advances and changes in demographics.

Pulmonary function and toxicities of proton versus photon for limited-stage small cell lung cancer.

PURPOSE: We aimed to compare the oncological outcomes and toxicities of definitive proton beam therapy (PBT) and photon beam therapy in patients with limited-stage small cell lung cancer (LS-SCLC). MATERIALS AND METHODS: We retrospectively reviewed 262 patients with newly diagnosed LS-SCLC who underwent definitive PBT (n = 20; proton group) or photon beam therapy (n = 242; photon group) with concurrent chemotherapy between January 2016 and February 2021 and compared overall survival (OS), progression-free survival (PFS), dose-volume parameters, and toxicities between the groups. RESULTS: The median follow-up duration was 24.5 months (range, 3.7 to 78.7). Baseline lung function was significantly worse and clinical target volume (CTV) was larger in the proton group (CTV: 296.6 vs. 215.3 mL; p = 0.080). The mean lung V10 was 37.7% ± 16.8% and 51.6% ± 24.5% in the proton and photon groups, respectively (p = 0.002). Two-year OS and PFS rates were 57.2% and 35.7% in the proton group and 65.3% and 40.8% in the photon group, respectively (p = 0.542 and 0.748, respectively). Grade ≥2 radiation pneumonitis and esophagitis occurred in 5 (25.0%) and 7 (35.0%) PBT-treated patients and 66 (27.3%) and 40 (16.5%) photon beam therapy-treated patients, respectively (p = 0.826 and 0.062, respectively). CONCLUSION: Although the proton group had poorer lung function and a larger CTV than that in the photon group, both groups exhibited comparable treatment outcomes and radiation-related toxicities in LS-SCLC. PBT may be a valuable therapeutic modality in patients with poor pulmonary function or extensive disease burden owing to its lung-sparing ability.

Dosimetric comparison between VMAT plans using the fast-rotating O-ring linac with dual-layer stacked MLC and helical tomotherapy for nasopharyngeal carcinoma.

BACKGROUND: To compare the dosimetric profiles of volumetric modulated arc therapy (VMAT) plans using the fast-rotating O-ring linac (the Halcyon system) based on a dual-layer stacked multi-leaf collimator and helical tomotherapy (HT) for nasopharyngeal cancer (NPCa). METHODS: For 30 NPCa patients, three sets of RT plans were generated, under the same policy of contouring and dose constraints: HT plan; Halcyon VMAT plan with two arcs (HL2arc); and Halcyon VMAT plan with four arcs (HL4arc), respectively. The intended dose schedule was to deliver 67.2 Gy to the planning gross target volume (P-GTV) and 56.0 Gy to the planning clinical target volume (P-CTV) in 28 fractions using the simultaneously integrated boost concept. Target volumes and organ at risks dose metrics were evaluated for all plans. Normal tissue complication probabilities (NTCP) for esophagus, parotid glands, spinal cord, and brain stem were compared. RESULTS: The HT plan achieved the best dose homogeneity index for both P_GTV and P_CTV, followed by the HL4arc and L2arc plans. No significant difference in the dose conformity index (CI) for P_GTV was observed between the HT plan (0.80) and either the HL2arc plan (0.79) or the HL4arc plan (0.83). The HL4arc plan showed the best CI for P_CTV (0.88), followed by the HL2arc plan (0.83) and the HT plan (0.80). The HL4arc plan (median, interquartile rage (Q1, Q3): 25.36 (22.22, 26.89) Gy) showed the lowest Dmean in the parotid glands, followed by the HT (25.88 (23.87, 27.87) Gy) and HL2arc plans (28.00 (23.24, 33.99) Gy). In the oral cavity (OC) dose comparison, the HT (22.03 (19.79, 24.85) Gy) plan showed the lowest Dmean compared to the HL2arc (23.96 (20.84, 28.02) Gy) and HL4arc (24.14 (20.17, 27.53) Gy) plans. Intermediate and low dose regions (40-65% of the prescribed dose) were well fit to the target volume in HL4arc, compared to the HT and HL2arc plans. All plans met the dose constraints for the other OARs with sufficient dose margins. The between-group differences in the median NTCP values for the parotid glands and OC were < 3.47% and < 1.7% points, respectively. CONCLUSIONS: The dosimetric profiles of Halcyon VMAT plans were comparable to that of HT, and HL4arc showed better dosimetric profiles than HL2arc for NPCa.

Clinical Outcomes Following Proton and Photon Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer.

We aimed to report the clinical outcomes following stereotactic body radiation therapy (SBRT) using photon or proton equipment in early-stage lung cancer. We retrospectively reviewed 202 cT1-2N0M0 lung cancer patients who underwent SBRT with 60 Gy in four consecutive fractions between 2010 and 2019 at our institution: 168 photon SBRT and 34 proton SBRT. Patients who underwent proton SBRT had relatively poor baseline lung condition compared to those who underwent photon SBRT. Clinical outcomes were comparable between treatment modalities: 5-year local control (90.8% vs. 83.6%, p = 0.602); progression-free survival (61.6% vs. 57.8%, p = 0.370); overall survival (51.7% vs. 51.9%, p = 0.475); and cause-specific survival (70.3% vs. 62.6%, p = 0.618). There was no statistically significant difference in grade ≥ 2 toxicities: radiation pneumonitis (19.6% vs. 26.4%, p = 0.371); musculoskeletal (13.7% vs. 5.9%, p = 0.264); and skin (3.6% vs. 0.0%, p = 0.604). In the binary logistic regression analysis of grade ≥3 radiation pneumonitis, poor performance status and poor baseline diffusion capacity of lung for carbon monoxide were significant. To summarize, though patients with high risk of developing lung toxicity underwent proton SBRT more frequently, the SBRT techniques resulted in comparable oncologic outcomes with similar toxicity profiles. Proton SBRT could be considered for patients at high risk of radiation pneumonitis.

Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer.

This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy.

Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx.

PURPOSE: This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT). MATERIALS AND METHODS: Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients. RESULTS: With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS. CONCLUSION: Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.

Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models.

Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT.

Feasibility of an Interactive Health Coaching Mobile App to Prevent Malnutrition and Muscle Loss in Esophageal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy: Prospective Pilot Study.

BACKGROUND: Excessive muscle loss is an important prognostic factor in esophageal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT), as reported in our previous research. OBJECTIVE: In this pilot study, we prospectively tested the feasibility of a health coaching mobile app for preventing malnutrition and muscle loss in this patient population. METHODS: Between July 2019 and May 2020, we enrolled 38 male patients with esophageal cancer scheduled for NACRT. For 8 weeks from the start of radiotherapy (RT), the patients used Noom, a health coaching mobile app that interactively provided online advice about food intake, exercise, and weight changes. The skeletal muscle index (SMI) measured based on computed tomography and nutrition-related laboratory markers were assessed before and after RT. We evaluated the changes in the SMI, nutrition, and inflammatory factors between the patient group that used the mobile app (mHealth group) and our previous study cohort (usual care group). Additionally, we analyzed the factors associated with walk steps recorded in the app. RESULTS: Two patients dropped out of the study (no app usage; treatment changed to a definitive aim). The use (or activation) of the app was noted in approximately 70% (25/36) of the patients until the end of the trial. Compared to the 1:2 matched usual care group by propensity scores balanced with their age, primary tumor location, tumor stage, pre-RT BMI, and pre-RT SMI level, 30 operable patients showed less aggravation of the prognostic nutritional index (PNI) (-6.7 vs -9.8; P=.04). However, there was no significant difference in the SMI change or the number of patients with excessive muscle loss (∆SMI/50 days >10%). In patients with excessive muscle loss, the walk steps significantly decreased in the last 4 weeks compared to those in the first 4 weeks. Age affected the absolute number of walk steps (P=.01), whereas pre-RT sarcopenia was related to the recovery of the reduced walk steps (P=.03). CONCLUSIONS: For esophageal cancer patients receiving NACRT, a health care mobile app helped nutritional self-care with less decrease in the PNI, although it did not prevent excessive muscle loss. An individualized care model with proper exercise as well as nutritional support may be required to reduce muscle loss and malnutrition.

Physical and Biological Characteristics of Particle Therapy for Oncologists.

Particle therapy is a promising and evolving modality of radiotherapy that can be used to treat tumors that are radioresistant to conventional photon beam radiotherapy. It has unique biological and physical advantages compared with conventional radiotherapy. The characteristic feature of particle therapy is the "Bragg peak," a steep and localized peak of dose, that enables precise delivery of the radiation dose to the tumor while effectively sparing normal organs. Especially, the charged particles (e.g., proton, helium, carbon) cause a high rate of energy loss along the track, thereby leading to high biological effectiveness, which makes particle therapy attractive. Using this property, the particle beam induces more severe DNA double-strand breaks than the photon beam, which is less influenced by the oxygen level. This review describes the general biological and physical aspects of particle therapy for oncologists, including non-radiation oncologists and beginners in the field.

Factors to improve distress and fatigue in Cancer survivorship; further understanding through text analysis of interviews by machine learning.

BACKGROUND: From patient-reported surveys and individual interviews by health care providers, we attempted to identify the significant factors related to the improvement of distress and fatigue for cancer survivors by text analysis with machine learning techniques, as the secondary analysis using the single institute data from the Korean Cancer Survivorship Center Pilot Project. METHODS: Surveys and in-depth interviews from 322 cancer survivors were analyzed to identify their needs and concerns. Among the keywords in the surveys, including EQ-VAS, distress, fatigue, pain, insomnia, anxiety, and depression, distress and fatigue were focused. The interview transcripts were analyzed via Korean-based text analysis with machine learning techniques, based on the keywords used in the survey. Words were generated as vectors and similarity scores were calculated by the distance related to the text's keywords and frequency. The keywords and selected high-ranked ten words for each keyword based on the similarity were then taken to draw a network map. RESULTS: Most participants were otherwise healthy females younger than 50 years suffering breast cancer who completed treatment less than 6 months ago. As the 1-month follow-up survey's results, the improved patients were 56.5 and 58.4% in distress and fatigue scores, respectively. For the improvement of distress, dyspepsia (p = 0.006) and initial scores of distress, fatigue, anxiety, and depression (p < 0.001, < 0.001, 0.043, and 0.013, respectively) were significantly related. For the improvement of fatigue, economic state (p = 0.021), needs for rehabilitation (p = 0.035), initial score of fatigue (p < 0.001), any intervention (p = 0.017), and participation in family care program (p = 0.022) were significant. For the text analysis, Stress and Fatigue were placed at the center of the keyword network map, and words were intricately connected. From the regression anlysis combined survey scores and the quantitative variables from the text analysis, participation in family care programs and mention of family-related words were associated with the fatigue improvement (p = 0.033). CONCLUSION: Common symptoms and practical issues were related to distress and fatigue in the survey. Through text analysis, however, we realized that the specific issues and their relationship such as family problem were more complicated. Although further research needs to explore the hidden problem in cancer patients, this study was meaningful to use personalized approach such as interviews.