High-dose Radiotherapy Research Articles

Case report: The role and value of radiotherapy in treatment of inflammatory myofibroblastic tumor

BackgroundInflammatory myofibroblastic tumors (IMTs) are rare soft-tissue neoplasms. Accordingly, there is no standardized therapy for unresectable or advanced IMT. Chemotherapy, radiotherapy, and targeted molecular therapy play an important role in unresectable or advanced IMT.Case presentationWe present a 54-year-old man with a cough and chest distress case report. The thoracic surgeon performed the right upper pulmonary occupying lesion wedge resection and enlarged lymph node excision biopsy. Pathologic diagnosis revealed that the morphology of “right upper lung mass” was considered as Inflammatory Myofibroblastic Tumor (IMT). Radiotherapy was indicated at a high dose: 5400cGy in 27 fractions of 2Gy over 5 weeks were delivered combined with cisplatin. The patient was given a CT/MRI and hematological index every 3 months and experienced no more adverse events. The patient survives with no tumor recurrence as of the last follow-up. Progression-free survival (PFS) exceeded 5 years.ConclusionsWe have reviewed the literature and summarized and discussed the radiotherapy treatment options and challenges for IMT. We first reported high-dose radiotherapy combined with chemotherapy treatment for unresectable IMT. Concurrent radiochemotherapy may be considered an intensive treatment for local progress, local recurrence, and nonresectable IMT patients.

Perianal leiomyosarcoma as a rare sequela of rectal cancer radiotherapy: a case report

Radiation-induced sarcomas (RIS) are iatrogenic malignancies that arise following high-dose radiotherapy, posing a significant clinical challenge due to their poor prognosis and resistance to conventional treatments. The incidence of RIS is increasing with advancements in radiotherapy techniques. This report presents a case of a 71-year-old male diagnosed with stage III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and curative surgery. Three years postoperatively, he developed a low-grade radiation-induced leiomyosarcoma in the perianal region. Histopathological examination confirmed a spindle cell neoplasm with notable immunohistochemical markers. RIS often presents as aggressive high-grade tumors resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment. This case underscores the importance of long-term surveillance post-radiotherapy and highlights the need for innovative therapeutic strategies, including immunotherapy. Despite being rare, RIS poses a significant risk following cancer treatment, making early detection through vigilant monitoring and advancements in therapeutic approaches crucial for improving patient outcomes.

Stereotactic arrhythmia radioablation - A systematic review and meta-analysis of the prospective clinical studies

Abstract Background Stereotactic arrhythmia radioablation (STAR) is increasingly being evaluated in prospective studies as a new promising treatment option for patients with therapy-refractory ventricular tachycardia (VT). In STAR, the VT substrate is noninvasively treated with a high dose of radiotherapy. Recently, several single-arm prospective studies evaluating the clinical outcomes of STAR were published. Considering that the evidence base consists mainly of retrospective case series, we conducted a systematic review and meta-analysis to synthesize the prospective data on outcomes of STAR. Purpose To perform a systematic review and meta-analysis of prospective studies evaluating clinical outcomes of STAR for VT. Methods This study was registered in PROSPERO and adhered to the PRISMA reporting guidelines. Full-text studies describing prospective studies evaluating the safety and efficacy of STAR for VT were included in this study. Records published until August 2023 were retrieved from OVID MEDLINE, OVID Embase, Web of Science Core Collection, the Cochrane Central Register of Controlled Trials, and Google Scholar search engine (top 200 hits), deduplicated, and screened for eligibility. Abstract screening, full-text screening, data extraction and quality assessment were performed by two reviewers independently. Endpoints were defined as treatment related CTCAE grade ≥3 adverse events within 90 days after treatment, overall survival (OS), time to VT recurrence, and recurrence-free survival. Rates of patients achieving pre-defined 50%, 75% and 95% VT burden reduction thresholds were summarised. Random-effects generalized linear mixed-effects models and inverse variance models were used for the meta-analysis. Results 1861 records were identified, 987 were screened, and 10 full-text manuscripts published between 2019 and 2023 describing the results of STAR in 82 patients were included in this study. The majority were male (n=72; 88%), between 45 and 85 years old, and suffered from ischaemic cardiomyopathy (n=51; 62%). Median left ventricular ejection fraction ranged from 21 to 38% between studies. 20 patients did not undergo a prior catheter ablation for VT. All patients were treated with a single dose of 25 Gy and median planned target volume ranged from 45 to 198 cc between studies. Pooled 12-month OS rate was 0.73, and the proportion of patients experiencing grade ≥3 adverse events within 90 days after STAR was 0.11 (Figure 1). Reduction in VT burden is shown in Table 1. Although these were not pooled because of large heterogeneity in VT reduction time frame definitions, it can be appreciated that most of the patients experienced a reduction in VT burden. Conclusion The increasing evidence from prospective studies on STAR shows acceptable 12-month OS in a population of patients with advanced heart failure and refractory VT. Moreover, there is a modest rate of high-grade adverse events and most patients experience a reduction in VT burden.

The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center

BackgroundRecurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies.Methods40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method.ResultsThe mean IORT dose was 13.8 Gy (range 10–18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95–14.881, p = 0.059 and HR 2.165 CI 95%: 0.916–5.114, p = 0.078ConclusionsThe survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.

Advantages of single high-dose radiation therapy compared with conventional fractionated radiation therapy in overcoming radioresistance

Background Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms. Methods Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions. Results 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice. Conclusions Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade

The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5–2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8+ T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations.

Involved-field high-dose chemoradiotherapy with respiratory motion management for esophageal squamous cell carcinoma.

We investigated the clinical outcomes of involved-field high-dose (≥66 Gy) chemoradiotherapy (CRT) combined with respiratory motion management for esophageal squamous cell carcinoma (ESCC). Patients who underwent definitive CRT for histologically confirmed ESCC in our department between 2012 and 2018 were retrospectively analyzed. Respiratory motion management strategies included breath-holding (63%) and mask immobilization (29%) based on individual measurements of respiratory tumor motion using radiographic fluoroscopy with endoscopically placed clip markers as landmarks. We evaluated patient characteristics, treatment efficacy, failure patterns, and toxicities. We enrolled 35 patients with a prescribed dose of 66-70 Gy in 33-35 fractions. The overall response rate within 6 months post-CRT was 94.3%; the median follow-up period for survivors was 43 months. The 2-year overall survival (OS), progression-free survival, and locoregional failure-free survival rates were 51.4%, 42.9%, and 42.9%, respectively. A significant difference in OS was observed between patients with and without esophageal fistulas after CRT (p = 0.002, log-rank test). Disease failure occurred in 16 patients (45.7%), including one (2.9%) with out-of-field regional nodal failure. Major grade 3 or higher toxicities included decreased white blood cell count (48.6%), neutrophil count (34.3%), and esophageal stenosis (31.4%). No grade 3 or higher cardiopulmonary toxicities were observed. Bronchial/tracheal tumor compression and a higher radiotherapy dose (70 Gy) were significantly correlated with esophageal fistulas. Involved-field high-dose CRT with respiratory motion management may be a feasible treatment option for ESCC. However, a comprehensive assessment of esophageal fistula risk is required to identify suitable candidates.

6955 A Rare Case of Rapidly Enlarging High Grade Follicular-Derived Carcinoma in a Young Patient - Formerly Known as Insular Thyroid Carcinoma with good response to Radioactive iodine ablation- A New Name, Same Aggressive Features

Abstract Disclosure: R. Abdelmasih: None. N. Prasad: None. N. Shah: None. Introduction: Follicular-derived thyroid carcinomas, formerly known as insular thyroid carcinomas, are an albeit rare but highly lethal thyroid carcinoma subtype with an incidence of 1-10% worldwide. It is known for its aggressive nature and comprises the majority of deaths from non-anaplastic follicular thyroid cancers. Case Presentation: A 30-year-old male presented with 2-year history of progressively enlarging painless right neck mass. Physical exam revealed 6x3 cm right well-circumscribed mobile mass not displacing the trachea. Head and neck CT showed 6.5 cm right thyroid mass with level 2A lymph node. Neck Ultrasound showed a 6.4 cm right thyroid nodule. Fine needle aspiration of the mass showed atypia of undetermined significance. Patient returned to clinic 1 year later with progressively enlarging right neck mass, now associated with dysphagia measuring 10 cm in physical exam deviating the trachea to the left. Repeat CT H&amp;N showed 10 cm right thyroid mass with moderate tracheal deviation and US showed 11 cm right heterogenous thyroid mass with regular margins and negative LNs. Patient underwent right thyroid lobectomy with surgical pathology showed 11.4 cm tumor with vascular invasion and no extrathyroidal extension. Pathology showed high grade follicular-derived Thyroid Carcinoma. Patient underwent completion thyroidectomy with benign pathology followed by radioactive iodine ablation 107.8 mCi I131 with successful targeting of residual thyroid tissue and no evidence of iodine avid distant metastasis. Patient has been followed closely for 2 years now with regular US, thyroglobulin level with recurrence. Discussion: Insular thyroid carcinomas are aggressive malignancies predominantly seen in females within the age of 55-65 though cases of young patients and children have been reported. Patients often present with enlarging goiter, dysphagia, and dyspnea however, metastatic disease to lymph nodes, lung and bone has also been reported as primary presentation in 20% of cases. Per literature review, recurrence and mortality rates have very wide range of 36-83% and 9-75% respectively which could be explained by a variety of prognostic factors including Patient age, tumor size, Macroscopic evident extrathyroidal extension, distant metastasis, or tumor necrosis. Often times insular thyroid carcinomas are mistaken for anaplastic carcinoma and thus fine needle aspiration is a helpful diagnostic tool to differentiate insular carcinoma. Pathology typically demonstrates well-defined insulae of thyroglobulin-filled follicles, necrotic foci, and high random mitotic activity. Treatment includes total thyroidectomy followed by high-dose radiotherapy. We Present this case to shed light on such a rare aggressive entity that requires early detection, belligerent management, and close follow-up for promising outcomes. Presentation: 6/3/2024

Long-Term Outcome of a Multicenter Prospective Study on Efficacy and Safety of High-Dose Stereotactic Body Radiation Therapy ≥48-h Interfraction Interval for ≤5 cm Hepatocellular Carcinoma

Introduction: The goal of this study was to evaluate the efficacy and safety of high-dose stereotactic body radiation therapy (SBRT) with an extended (48 h or more) interfraction interval for hepatocellular carcinoma (HCC) ≤5 cm in size after incomplete response to transarterial chemoembolization (TACE). Methods: This multicenter prospective study included 54 patients with inoperable HCC of ≤5 cm size between July 2012 and June 2015. A total SBRT dose of 60 Gy in 3 fractions was administered within 14 days with ≥48-h interfraction interval to patients who showed an incomplete response after 1–5 sessions of TACE. Treatment responses were defined according to the modified Response Evaluation Criteria for Solid Tumors. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results: Forty-eight patients were evaluated with a median follow-up period of 66 months (range, 2–126 months). The median tumor size was 2.0 cm (range, 1.0–4.5 cm), and most patients (87.5%) had a single lesion. The 1-, 2-, and 5-year local control (LC) rates were 100%, 94.8%, and 90.7%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates were 63.4%, 56.9%, and 24.9%, respectively. The 1-, 2-, and 5-year overall survival (OS) rates were 95.6%, 90.9%, and 76.5%, respectively. None of the patients experienced grade 3+ gastrointestinal toxicity, while 1 patient developed non-classic radiation-induced liver disease 2 months after SBRT. Conclusion: High-dose SBRT with a ≥48-h interfraction interval after incomplete response to TACE is effective for HCC ≤5 cm in size as evidenced by the high rates of LC and OS and acceptable treatment-related toxicity.

EP.13C.02 High-Dose Radiation Therapy for Limited-Stage Small-Cell Lung Cancer: Real-World Experience from Two Tertiary Centers

EP.13C.02 High-Dose Radiation Therapy for Limited-Stage Small-Cell Lung Cancer: Real-World Experience from Two Tertiary Centers

The Role of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients: A Literature Review

Background: Globally, hepatocellular carcinoma (HCC) is the most prevalent kind of primary liver cancer. Treatment options for HCC include radiotherapy, immunotherapy, surgery, targeted therapy, transarterial chemoembolization, and hepatic arterial infusion chemotherapy. Limited efficacy was observed since 70-80% of cases are diagnosed late and unresectable. Growing evidence reported that SBRT is a viable option for locoregional treatments like radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) for patients who did not respond to those treatments. Methods: A thorough search of electronic databases including PubMed, Cochrane Library, and Embase was conducted for studies on Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma published in English over the past 10 years. The review process followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to ensure a systematic approach. Inclusion criteria encompassed studies focusing on SBRT use in HCC treatment, with extracted data synthesized to provide a comprehensive overview of current evidence. Any discrepancies during the review were resolved through consultation with a third reviewer when necessary. Results: In comparison to conventional radiation therapy, Stereotactic Body Radiation Therapy (SBRT) offers precise administration of the high dose of radiotherapy, given in fewer fractions, and may be used in conjunction with other therapy modalities. Global guidelines, including in Indonesia, have proposed the implementation of SBRT. Local control was reportedly achieved in around 90–95% of HCC patients. Multimodal therapies, combined with TACE, showed superior results regarding the local control and overall survival. SBRT may eventually become the definitive treatment for early-stage HCC patients and has a critical role as a transitional therapy for patients awaiting liver transplantation. Improved outcomes and quality of life were also observed in patients with portal vein thrombosis (PVT) and extrahepatic metastases who underwent SBRT. Conclusions: SBRT results in promising local control, raises overall survival, and improves the quality of life in HCC patients with various stages.

Short-Term Androgen Deprivation Therapy and High-Dose Radiotherapy in Intermediate- and High-Risk Localized Prostate Cancer: Results from the GETUG 14 Randomized Phase III Trial

Short-Term Androgen Deprivation Therapy and High-Dose Radiotherapy in Intermediate- and High-Risk Localized Prostate Cancer: Results from the GETUG 14 Randomized Phase III Trial

Dose escalation in radical radio(chemo)therapy for cervical and upper thoracic esophageal cancer with 3DCRT/IMRT (ChC&UES): a multicenter retrospective study

BackgroundCervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose.MethodWe retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50–55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55–63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS).ResultsThe median OS was 33.0 months (95% CI: 29.401–36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05).ConclusionHD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn’t improve survival but enhances ORR.

Clinical Outcomes of Carbon Ion Radiation Therapy for Malignant Peripheral Nerve Sheath Tumors

Purposeto investigate outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiotherapy (CIRT). Patients and methodswe retrospectively analyzed the outcome of 23 patients with MPNST treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of disease. Six (26%) of patients received neoadjuvant chemotherapy. The most frequent tumor site was brachial plexus (N=9; 39.1%). In five patients (21.7%) neurofibromatosis type 1 (NF1) disorder was found, while 4 patients (17, 4%) had radiation-induced MPNST. The median CIRT prescribed total dose was 69.8 Gy [RBE] (range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to CTV-LR of 45 Gy[RBE] (range, 41.4 – 54). ResultsAfter a median follow-up time of 23 months (range 3-100 months), the OS rates at 1-year and 2-year were respectively: 82.38%, 61.51%. The 1-year and 2-year LRFS rates were respectively: 65.07%, 48.80%; the 1-year and 2-year PFS rates were respectively: 56.37%, 40.99%. No patients showed acute or late Grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of Grade ≥2: dermatitis in 6 patients, mucositis in 2 patients, peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of Grade ≥2, mainly due to loco-regional neuropathy. Conclusionshigh dose CIRT shows favorable local effect with acceptable toxicities in patients with gross residual and LR after surgery, or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.

Analysis of factors related to radiation-induced oral mucositis in patients with head and neck tumors undergoing radiotherapy

ObjectiveTo explore the risk factors of radiation-induced oral mucositis (RIOM) in patients with head and neck tumors undergoing radiotherapy. MethodsA retrospective collection was conducted on patients with head and neck tumors who underwent radiotherapy and chemotherapy in our hospital from April 1, 2015 to April 1, 2019. They were divided into an incidence group (n = 48) and a non-incidence group (n = 76) based on whether RIOM occurred, and relevant data was collected for comparison. ResultsThere were statistically significant differences between the two groups of patients in terms of tumor type, smoking percentage, education level percentage, tumor stage, oral mucosal inflammation stage, radiotherapy dose, mucosal protectants, and oral hygiene condition(P < 0.05); The regression analysis results showed that smoking (OR=1.274, 95 % CI: 1.095–2.007), high-dose radiotherapy (OR=1.223, 95 % CI: 1.098–2.077), and poor oral hygiene (OR=1.367, 95 % CI: 1.024–2.890) were risk factors for RIOM. ConclusionSmoking, high-dose radiotherapy, and poor oral hygiene were risk factors for RIOM in head and neck patients after radiotherapy and chemotherapy.

A phase 2 single-arm trial of high-dose precision targeted radiotherapy added to immunotherapy for patients with metastatic non-small cell lung cancer.

For metastatic non-small cell lung cancer (NSCLC), the addition of radiotherapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS). In this single arm phase 2 trial, 45 patients with metastatic NSCLC who had received an anti-PD-1/anti-PD-L-1 ICI for 4+ weeks were enrolled from July 2017-May 2021. Patients received high-dose RT to 1-4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing to a historical control rate of 35%. Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1 positive. Median number of treated tumors was two and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI 44-75%), higher than the historical control rate (p<0.001). Median PFS was 6.9 months (95% CI 4.0-13.5 mo) and median OS was 27.4 months (95% CI 20.4-not reached). Several patients with pre-study disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at one, two, and three years. Two dose-limiting toxicities were observed (5%), including one grade 5 pneumonitis. The strategy improved 24-week PFS compared to historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.

Radiation-induced liver disease mimicking liver metastasis after low-dose hepatic irradiation during radiotherapy for gastric mucosa-assisted lymphoid tissue lymphoma: A case report.

Radiation-induced liver disease (RILD) is an established complication of hepatic irradiation that is typically reported in patients receiving high-dose radiotherapy for hepatocellular carcinoma or liver metastases. However, RILD can also occur after unintentional low-dose liver exposure during radiotherapy for other gastrointestinal malignancies when careful precautions are not taken. We report the case of a 44-year-old woman with gastric mucosa-associated lymphoid tissue lymphoma who underwent salvage radiotherapy administered to the entire stomach. One month after completing this radiotherapy, computed tomography and magnetic resonance imaging of the patient's abdomen revealed a 4 cm lesion in the left lateral liver segment, suggestive of metastasis. An ultrasound-guided biopsy was performed, and the histopathological findings were consistent with those of RILD. Conservative management was pursued with close monitoring of liver function tests. The patient's imaging findings and liver enzyme levels normalized approximately 3 months after the initial diagnosis. This case highlights the importance of considering RILD in the differential diagnosis of new hepatic lesions detected after radiotherapy, even in patients with low-dose liver exposure within generally acceptable limits. Careful correlation with the radiotherapy plan is crucial to avoid misdiagnosing RILD as metastatic disease and to guide appropriate management.

High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial

For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003. From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit. Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option. Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program.

The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients.

Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006-2014, and the post CPP implementation group constituted patients diagnosed 2016-2019. We evaluated timing of RT and survival in relation to CPP implementation. A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4-6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.

The Landscape of Stereotactic Ablative Radiotherapy (SABR) for Renal Cell Cancer (RCC).

Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.