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Pencil-beam scanning proton therapy has been considered a potential modality for the 3D form of spatially fractionated radiation therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans. Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using 2-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross target volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in the treatment of 2 patients and their dosimetric parameters were reported. The RPL strategy was able to achieve the clinical planning goals. Compared to previously treated photon plans, the average number of vertices increased by 30%, the average vertex volume by 49% (18.2 ± 25.9 cc vs 12.2 ± 14.5 cc, P =.21), and higher PVDR (10.5 ± 4.8 vs 2.5 ± 0.9, P <.005) was achieved. In addition, RPL plans show more conformal dose with less low dose to GTV (V30%, 60.9% ± 7.2% vs 81.6% ± 13.9% and V10%, 88.3% ± 4.5% vs 98.6% ± 3.6% [ P <.01]). The RPL plan for 2 treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively. A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans. [ABSTRACT FROM AUTHOR]

This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiation therapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiation therapy of ≥40 Gy radiation dose to primary lesion, from 4 academic cancer centers between October 2018 and December 2022. Propensity score matching was conducted to minimize the potential confounding effects. In the overall cohort of 409 patients, the group that received additional radiation therapy had superior overall survival (OS) (hazard ratio [HR], 0.51; 95% CI, 0.39-0.66; P <.001) and progression-free survival (PFS) (HR, 0.52; 95% CI, 0.40-0.66; P <.001) compared to the group that received chemoimmunotherapy alone. After 1:1 propensity score matching, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiation therapy significantly improved OS and PFS (median OS, 24.9 vs 14.6 months; P =.003; median PFS, 14.2 vs 10.6 months; P =.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiation therapy was an independent prognostic factor for both OS (HR, 0.57; 95% CI, 0.41-0.81) and PFS (HR, 0.63, 95% CI, 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with nonregional lymph node metastases only who received radiation therapy (HR, 0.49; 95% CI, 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR, 0.72; 95% CI, 0.46-1.13). Regarding safety, the group receiving additional radiation therapy had higher incidences of grade 3 to 4 lymphopenia (74.4% vs 17.7%, P <.001) and esophagitis (11.2% vs 2.4%, P =.006). The addition of radiation therapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with nonregional lymph node metastasis. [ABSTRACT FROM AUTHOR]

The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF – Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful. Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more. Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiation therapy. Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity-modulated radiation therapy (moderate hypofractionated radiation therapy [MHRT], stereotactic body radiation therapy [SBRT]), were included in this study. Severity and duration of urinary symptoms observed during serial follow-up after at least 3 months from radiation therapy were graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 using information from a prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analyzed with univariable and multivariable binary logistic regression. A total of 203 eligible patients were included (MHRT = 114, 64-68 Gy/25#; SBRT = 89, 35-37.5 Gy/5#). Median time from TURP to radiation therapy was 10 months (IQR, 7-16 months), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17 cc (IQR, 0.5-1.35 cc), whereas in MHRT and SBRT groups it was 1.03 cc (IQR, 0.4-1.15 cc) and 1.27 cc (IQR, 0.5-1.4 cc), respectively. At a median follow-up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n = 17) and 23.2% (n = 47), respectively. Grade 3 symptoms were observed at median 29 months (IQR, 19-62 months) after radiation therapy completion, lasting for a median duration of 8 months (IQR, 2-14 months). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiation therapy, fraction size, prostate volume, TURP to radiation therapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiation therapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiation therapy. [ABSTRACT FROM AUTHOR]

Memantine is standard in certain adults receiving brain radiation therapy (RT) to decrease cognitive impacts, but it is unknown whether pediatric patients can take, tolerate, and/or benefit from memantine. In this prospective single-arm feasibility study, we hypothesized that pediatric patients receiving central nervous system (CNS) RT would tolerate memantine with good adherence. Patients aged 4 to 18 years with a primary CNS malignancy (excluding World Health Organization grade 4 astrocytoma, glioblastoma) receiving intracranial RT were eligible. A 6-month memantine course was given during and after RT, with dose titration in 5 mg increments over 4 weeks targeting a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg twice a day. The primary endpoint was to achieve 80% drug adherence rate in 80% of patients measured 1 month after RT. Secondary objectives included memantine feasibility at 3 and 6 months. Eighteen patients enrolled from 2020 to 2022 and were prescribed memantine with RT. The study closed early to avoid competing with the phase 3 randomized Children's Oncology Group study ACCL2031. No predefined stopping rules were met. One patient withdrew for cognition-altering substance use, leaving 17 patients available for analysis. One patient discontinued memantine after one dose due to nausea. For the remaining 16 patients, there was a median of 100% pill completion rate (range, 74%-100%; n = 9/17 with 100% adherence) at 1 month after RT, with 15/16 (94%) with adherence rates >80%. At the 3- and 6-month post-RT time points for secondary endpoints, the median adherence rates were 100% (range, 55%-100%) and 96% (range, 33%-100%), respectively. Grade 1 to 2 fatigue, headache, and nausea were the most common toxicity events, at least possibly related to the study drug (n = 27), without attributable grade 3+ events. Memantine is a feasible, safe, and well-tolerated addition to multimodality treatment for pediatric CNS malignancies. Results of ACCL2031 are awaited to define the value of memantine in this population. [ABSTRACT FROM AUTHOR]

Acute radiation dermatitis (ARD) is the most common side effect reported by patients undergoing radiation therapy (RT). Currently, the assessment of the severity of the reaction is based on the visual assessment of the skin, which is a subjective method, depending on many factors. The main aim of this study was to investigate the usefulness of hyperspectral imaging (HSI) in the assessment of ARD and find physiological factors that could be correlated with ARD. In this clinical pilot trial, weekly acquisitions of hyperspectral camera images of irradiated skin were performed for 5 weeks of RT and at the posttreatment follow-up visit which took place 30 to 40 days after the last fraction of RT. At the same time, the severity of radiodermatitis was assessed based on the criteria of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). The content and concentration of chromophores in irradiated skin were quantitatively determined using a hyperspectral camera. The use of HSI supported by image analysis and processing methods allowed for the determination of the content and distribution of hemoglobin and melanin in the irradiated skin. It was found that the hemoglobin concentration is correlated with the subjective assessment made according to the CTCAE protocol. HSI is a sensitive and specific method of analyzing the concentration of chromophores in the skin, including hemoglobin. A clear correlation was found between hemoglobin concentration and CTCAE v.5 scale because of which HSI can be considered as an objective method of skin assessment during RT. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM), although a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiation therapy. This study sought to elucidate the significance of the prescription dose by employing time-dose-response models for patients with UM receiving photon-based stereotactic radiosurgery (SRS). The analysis included patients with UM treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into 3 dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose-response models for LC were created at 2, 4, and 7 years after SRS using maximum-likelihood fitted logistic models. Outcomes from 594 patients with 594 UMs were used to create time-dose-response models. The prescribed doses and the number of patients were as follows: 17 to 19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose-response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For 4 years and a LC of 90%, a dose of approximately 21 Gy was required. After 7 years, the 21 Gy prescription dose was predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy. In contrast to prior findings, the time-dose-response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly. [ABSTRACT FROM AUTHOR]

Primary soft tissue sarcoma (STS) is rare, with many tumors occurring in extremities. Local management is limb-sparing surgery and preoperative/postoperative radiation therapy (RT) for patients at high risk of local recurrence. We prospectively investigated late normal tissue toxicity and limb function observed after intensity modulated RT (IMRT) in extremity STS. Patients with extremity STS, age ≥16 years. Two treatment cohorts: IMRT 50 Gy in 25 × 2 Gy fractions (preoperative) or 60/66 Gy in 30/33 × 2 Gy fractions (postoperative). The primary endpoint was the rate of grade ≥2 late soft tissue fibrosis (subcutaneous tissue) at 24 months after IMRT (Radiation Therapy Oncology Group late radiation morbidity scoring). One hundred sixty-eight patients were registered between March 2016 and July 2017. Of those, 159 (95%) received IMRT (106, 67% preoperative RT; and 53, 33% postoperative RT) with a median follow-up of 35.2 months (IQR, 32.9-36.6); 62% men, median age 58 years. Of 111 patients assessable for the primary endpoint at 24 months, 12 (10.8%; 95% CI, 5.7%-18.1%) had grade ≥2 subcutaneous fibrosis. The overall rate at 24 months of Radiation Therapy Oncology Group late skin, bone, and joint toxicity was 7 of 112 (6.3%), 3 of 112 (2.7%), and 10 of 113 (8.8%), respectively, and for Stern's scale edema was 6 of 113 (5.3%). More wound complications were observed with preoperative than postoperative RT (29.2% vs 3.8%). Overall survival at 24 months was 84.6%, and the local recurrence event rate at 24 months was 10%. The rate of grade ≥2 subcutaneous fibrosis at 24 months after IMRT was 10.8%, consistent with other recent trials of IMRT and lower than historically reported rates in patients treated with 3-dimensional conformal RT. This trial provides further evidence for the benefits of IMRT in this patient population. [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize the conditional risk of developing grade 2+ urinary or gastrointestinal (GI) toxicity for patients treated with external beam radiation therapy in Radiation Therapy Oncology Group 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and at later points of follow-up. One thousand five hundred thirty-two patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1499 were eligible and included in data analysis with a median follow-up of 8.4 years (range, 0.02-13 years). Patients were treated with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy according to institutional practice without the addition of androgen deprivation and randomized to receive either standard-dose radiation therapy of 70.2 Gy or dose-escalated radiation therapy of 79.2 Gy of radiation therapy to the prostate only with standard fractionation. Univariate and multivariate analyses were performed to determine whether initial factors were predictive of late toxicity at the time of treatment and at later time points. As patients proceed further from completion of radiation therapy without the development of toxicity, the subsequent risk of both grade 2+ genitourinary (GU) and GI toxicity decreases with time. At the time of enrollment, the risk of developing grade 2+ toxicity over the next 5 years was 9.57% and 17.89%, respectively. After 5 years of toxicity-free survival, the risk of developing grade 2+ GU or GI toxicity in the subsequent 5 years was 3.02% and 1.54%, respectively. Baseline treatment and patient-related factors predicted late toxicity both at trial enrollment and after 2 years of toxicity-free survivorship. Baseline urinary dysfunction and dose-escalated radiation therapy were associated with increased late GU toxicity. Acute GI toxicity and dose-escalated radiation therapy were associated with increased risk of late GI toxicity. Treatment with intensity-modulated radiation therapy was associated with reduced risk of either toxicity. The conditional risk of grade 2+ toxicities decreases as patients proceed further from treatment, with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points. [ABSTRACT FROM AUTHOR]

With the coming era of digital medicine and healthcare technology, mathematical modeling of tumors has become a key step to optimize and realize precision radiation therapy. The purpose of this study was to develop a mathematical model for simulating the change of head and neck (HN) tumor volume during radiation therapy. A formula was developed to describe the dynamic change of oxygenated compartment within a tumor, which was combined with the lethal lesions model to describe various cell processes during radiation therapy, including potentially lethal lesion repair and misrepair, cell proliferation/loss, and tumor reoxygenation. Parameter sensitivity analysis was performed to evaluate the impacts of lesion- and repair-related biological factors on radiation therapy outcomes. We tested our model on 14 available patients with HN cancer and compared the performance with 3 other models. The mean error of our model for the 12 good fit cases was 12.2%, which is considerably smaller than that of the linear quadratic model (19.7%), the generalized linear quadratic model (19.1%), and a 4-level cell population model (16.6%). Correlation analysis results revealed that for small tumors, there was a positive correlation (correlation coefficient r = 0.9416) between hypoxic fraction (hf) and tumor volume, whereas the correlation became negative and not significant (r = − 0.4365) for large tumors. It is demonstrated from sensitivity analysis that the production rate of lethal lesions (η l) has a far greater impact on tumor volume than other parameters. The hf had an insignificant impact on tumor volume but had a notable influence on the volume of surviving cells. The final volume of surviving cells at h f = 0.5 was almost 8 × 10 2 times that of h f = 0.01. The potentially lethal lesion-related parameters (the production rate of potentially lethal lessions per unit dose η p l , the rate of correct repair per unit time ε p l , and the rate of binary misrepair per unit time ε 2 p l) had rather small impacts (<1%) on both tumor volume and the volume of surviving cells, which indicates that the repaired and misrepaired sublethal cells only take up a small portion of the total cancer cell population. A population-based tumor-volume model for HN cancer during radiation therapy with a dynamic oxygenated compartment was developed in this study. Comprehensively considering the damage process of tumor cells caused by radiation therapy, the accurate prediction of the volume change of HN tumors during treatment was revealed. Meanwhile, various cell activities and their principles in the process of antitumor treatment were reflected, which has positive clinical reference significance for radiobiology. [ABSTRACT FROM AUTHOR]

For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values. [ABSTRACT FROM AUTHOR]

This study reports the development and evaluation of yttrium-90 (90Y) radiolabeled silica-coated iron oxide (SiO 2 -Fe 3 O 4) resin microspheres for potential theranostic application in cancer radiation therapy. Iron oxide nanoparticles of average diameter 29.7 nm were synthesized via optimized co-precipitation and displayed superparamagnetic behavior ideal for MRI. Aminosilane surface functionalization enabled covalent conjugation of 1 mmol/g DTPA/DOTA chelators for labeling 2 mCi 90Y per 150 μg nanoparticles with 92 % efficiency when incubated for 45 mins at pH 5.5 and 50°C. In vitro stability assays in buffers and human serum showed excellent 90Y retention (>95 %) up to 48 hours. In vivo biodistribution in Wistar rats revealed extended nanoparticle circulation half-life of 5.2 hours and peak exposure of 22.4 %ID/g compared to rapid clearance of unconjugated 90Y chloride within 1 hour. Complete renal recovery by 72 hours and minimal bone accumulation (<2 %) proves in vivo stability and biocompatibility of the 90Y-radiolabeled theranostic platform. [ABSTRACT FROM AUTHOR]

Radiation oral mucositis (RIOM) is one of the most common side effects of radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). The nutritional status of the body is an important factor affecting the efficacy of radiotherapy and chemotherapy, as well as the prognosis of patients. The aim of the study was to explore the relationship between nutrition counseling (NC) and radiation-induced oral mucositis (RIOM), and to provide a reference for the prevention and treatment of RIOM in clinical practice. We conducted a retrospective cohort study using the data among 147 NPC patients who received radical radiotherapy. Patients were divided into NC group and control group and radiation-induced Oral Mucositis (RIOM) classification i.e. mild RIOM (grade 0–1 group) and severe RIOM (grade ≥ 2 group). Univariate and multivariate analyses were used to analyze the association between baseline data of the patients and severity of RIOM. Of the 147 patients with NPC, there were 46.9% (69/147) patients who received NC, while control group accounted for 53.1% (78/147). There was no statistically significant difference in age, gender, stage, smoking, drinking, body mass index (BMI) before RT, Patient Generated Subjective Global Assessment (PG-SGA) score and Hospital Anxiety and Depression Scale (HADS) score between NC group and control group. However, there was a significant difference in the incidence of severe RIOM patients between NC group and control group (40.6% vs. 69.2%). Univariate analysis showed that NPC patients had PG-SGA score ≥ 4 (P < 0.001; HR : 0.14; 95% CI: 0.04–0.45), the amplitude of weight loss (WL) ≥ 3% (P < 0.001; HR: 0.62; 95% CI: 0.50–0.77), lower hemoglobin (P = 0.01; HR: 0.97; 95% CI: 0.95–0.99) and patients with NC (P < 0.001; HR: 3.24; 95% CI: 1.64–6.40) were significantly associated with severe RIOM. Multivariate analysis showed that PG-SGA ≥ 4 (P = 0.23; HR: 0.23; 95% CI: 0.06–0.86) and WL ≥ 3% (P < 0.001; HR: 0.63; 95% CI: 0.50–0.80) were risk factors for severe RIOM, whereas receiving nutrition consultation was a protective factor (P = 0.03; HR: 2.49; 95% CI: 1.09–5.66). NC was beneficial in reducing severe RIOM and PG-SGA ≥ 4. WL ≥ 3% exacerbate severe RIOM. [ABSTRACT FROM AUTHOR]

Men having postoperative radiotherapy after radical prostatectomy usually have a favourable outcome. The results of RADICALS-HD will help patients and their clinicians decide on the duration of androgen deprivation therapy with postoperative radiotherapy. Future trials should focus on patients at a higher risk of metastases. The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term. Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles. Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54–1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison. Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently. [ABSTRACT FROM AUTHOR]

This review systematically investigates the role of radiomics in radiotherapy, with a particular emphasis on the use of quantitative imaging biomarkers for predicting clinical outcomes, assessing toxicity, and optimizing treatment planning. While the review encompasses various applications of radiomics in radiotherapy, it particularly highlights its potential for guiding reirradiation of recurrent cancers. A systematic review was conducted based on a Medline search with the search engine PubMed using the keywords "radiomics or radiomic" and "radiotherapy or reirradiation". Out of 189 abstracts reviewed, 147 original articles were included in the analysis. These studies were categorized by tumor localization, imaging modality, study objectives, and performance metrics, with a particular emphasis on the inclusion of external validation and adherence to a standardized radiomics pipeline. The review identified 14 tumor localizations, with the majority of studies focusing on lung (33 studies), head and neck (27 studies), and brain (15 studies) cancers. CT was the most frequently employed imaging modality (77 studies) for radiomics, followed by MRI (46 studies) and PET (13 studies). The overall AUC across all studies, primarily focused on predicting the risk of recurrence (94 studies) or toxicity (41 studies), was 0.80 (SD = 0.08). However, only 24 studies (16.3%) included external validation, with a slightly lower AUC compared to those without it. For studies using CT versus MRI or PET, both had a median AUC of 0.79, with IQRs of 0.73–0.86 for CT and 0.76–0.855 for MRI/PET, showing no significant differences in performance. Five studies involving reirradiation reported a median AUC of 0.81 (IQR: 0.73–0.825). Radiomics demonstrates considerable potential in personalizing radiotherapy by improving treatment precision through better outcome prediction and treatment planning. However, its clinical adoption is hindered by the lack of external validation and variability in study designs. Future research should focus on implementing rigorous validation methods and standardizing imaging protocols to enhance the reliability and generalizability of radiomics in clinical radiotherapy, with particular attention to its application in reirradiation. [ABSTRACT FROM AUTHOR]

Trimodal therapy consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy, has emerged as a valuable therapeutic alternative to radical cystectomy in patients with muscle invasive bladder cancer. Concomitant radiosensitising chemotherapy is a component of trimodality increasing locoregional control compared to radiotherapy alone. The combinations 5-fluorouracil with mitomycin or cisplatin are the best supported in the literature. Gemcitabine appears to be a feasible and promising alternative. There is considerable international heterogeneity in terms of dose, volumes and fractionation. The most commonly used regimens are moderately hypofractionated (55 Gy in 20 fractions over 4 weeks) and normofractionated (64 Gy in 32 fractions) regimens. Radiotherapy for bladder cancer is an effective and evolving treatment, with current technical developments, and studies of new combinations with systemic treatments underway. [ABSTRACT FROM AUTHOR]

Due to the recent advances in the systemic treatment of non-small cell lung cancer, the management of locoregional recurrences, especially after initial radiotherapy (with or without concurrent chemotherapy), is of increasing significance. The potential alternatives in this setting include: a salvage local strategy (based on surgery, radiotherapy or thermoablative treatment), promising approach, but sometimes difficult to implement in often frail patients, and whose modalities remain under-researched; or alternatively, the initiation of systemic treatment, where the prognosis aligns with that of de novo metastatic patients. This comprehensive literature review focused on salvage radiotherapy treatment of recurrent non-small cell lung carcinomas, after initial radiotherapy, with or without associated systemic treatment. It aims to present the main findings on this area, from patient selection and preparation, to key characteristics, including dosimetric aspects, and the main limitations and uncertainties associated with this therapeutic modality. [ABSTRACT FROM AUTHOR]

Forte des nombreuses innovations cliniques, technologiques ou stratégiques, la radiothérapie est en évolution permanente, contribuant à des enjeux majeurs de qualité et de sécurité, dans un contexte où il est nécessaire de se conformer à de nouvelles exigences réglementaires. Nous décrivons dans cet article les conditions de mises en œuvre et d'application des exigences d'habilitation, de certification périodique et d'audit par les pairs en France. With numerous clinical, technological or strategic innovations, radiation therapy is constantly evolving, contributing to major quality and safety issues, in a context where new regulatory standards are required. In this article, we will describe the conditions for implementing and applying the requirements for accreditation, periodic certification and peer audit in France. [ABSTRACT FROM AUTHOR]

Electron radiotherapy has long been preferred to photons for the treatment of superficial lesions because of its physical characteristics (high dose at the surface, rapid decrease in depth). Other characteristics (penumbra, heterogeneity on an oblique or irregular surface) make them difficult to use. In most indications (skin cancers, head and neck, medulloblastoma), with technical progress, in some cases they have been replaced by intensity-modulated conformal radiotherapy, brachytherapy and contact therapy. Other indications (drainage of mesotheliomas or irradiation of benign lesions) have disappeared. The low frequency of use leads to problems of safety and cost-effectiveness. However, modern photon radiotherapy techniques are still less effective than electrons in specific indications such as total skin irradiation (mycosis fungoides) or certain thin chest wall irradiations after total mastectomy, reirradiation or paediatric treatments without protons. Flash therapy, initiated by electrons, has been developed over the last 10 years, providing high-dose irradiation in an extremely short time. Initial results show good efficacy, with fewer side effects than with conventional radiotherapy. These results are leading to clinical technological developments on a larger scale. Although it has been replaced in most indications by more modern techniques, electron radiotherapy remains essential for targeted indications in specialised centres. The emergence of flash therapy will lead to new indications, on machines equipped with this new technology, which have yet to be defined and are currently the responsibility of specialised teams. [ABSTRACT FROM AUTHOR]

Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/ TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin–paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. A total of 1095 patients were randomised (pembrolizumab, n = 545; placebo, n = 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P = 0.570]. Kaplan–Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n = 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n = 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. • This randomised study evaluated adjuvant pembrolizumab plus chemotherapy for newly diagnosed, high-risk endometrial cancer. • Adjuvant pembrolizumab plus chemotherapy did not improve DFS in the intention-to-treat population. • In prespecified subgroup analyses, the combination improved DFS in patients with dMMR tumours. • The safety profile of pembrolizumab plus chemotherapy was as expected and manageable. [ABSTRACT FROM AUTHOR]

The aim of the current study is to compare the dosimetry of 3 radiation therapy (RT) techniques used in the EORTC 22922/10925 trial for irradiating the internal mammary (IM) and medial supraclavicular nodes (MS) using a treatment planning system available nowadays for dose calculation. We performed a retrospective dosimetry analysis of anonymised data; thus, ethics approval was not required. Ten cases of left-sided breast were randomly selected for RT planning to a total dose of 50 Gy in 25 fractions. The treatment planning was done according to the trial's protocol and under the supervision of the EORTC trial's coordinators. Doses to planning target volumes (PTV) and to organs at risk (OARs) are reported. Data is presented in descriptive statistics. A total of 10 cases and 40 treatment plans (4 plans per case: standard -plan A, modified standard -plan B, individualised -plan C and breast-only –plan D). For all planning techniques, the mean dose to the PTV of the left breast (plan A-D) and the PTV-MS (plan A-C) exceeded 95% of the prescribed dose (>47.5 Gy). The individualised technique (plan C) had a lower coverage for PTV-IM, with a mean of 87% of the prescribed dose compared to ∼102% for plans A and B. The dose to OARs varied between techniques, with the mean heart dose being higher in the standard and modified standard techniques (18.3 and 16.6 Gy, respectively) compared to the individualised technique (9.5 Gy). The 3 RT techniques used in the trial varied in target coverage and OARs dose. Our results may help to understand the observed larger absolute benefit of individualised IM-MS treatment planning in terms of breast cancer outcomes. • The 3 radiation techniques used in the EORTC 22922/10925 trial to irradiate the internal mammary nodes and medial supraclavicular nodes varied in target coverage and organs at risk dose. • Variation between the 3 techniques were also per patient case. • This dosimetric study shows how radiation planning techniques can lead to significant differences dose coverage, organs at risk dose, and outcomes. • The inhomogeneity and extreme high doses in match line may explain the radiation side effects that match line fibrosis that were often observed in these patients. [ABSTRACT FROM AUTHOR]

The standard treatment of locally advanced cervical carcinoma is radical chemoradiation followed by brachytherapy which has improved survival. Hence, a major concern is our attempt to reduce the incidence of acute and late toxicities. IMRT has been shown to reduce toxicities. In this study, we have compared 3DCRT with IG-IMRT using patient-specific margins to evaluate tumor control as well as OAR-related toxicities. This was a single institution prospective phase III randomised control study including patients of squamous cell carcinoma of cervix (stage II–IIIB, FIGO 2009) without pelvic lymph node involvement. All patients were simulated using intermediate bladder filling protocol and those in the IG-IMRT arm, underwent additional scans with full and empty bladder to assess the range of internal motion and generate individualised ITV margin. EBRT dose of 46Gy/23#/4.5 weeks was delivered with weekly concurrent cisplatin followed by brachytherapy. All toxicities during EBRT and till 3 months post brachytherapy were considered acute toxicity. Post-treatment, patients were followed up every 2 months for first 2 years and then once every 6 months. Disease-related outcomes were assessed with clinical examination and symptom-directed imaging. Two hundred patients were screened for inclusion and of them, 89 patients in 3DCRT and 84 patients in IG-IMRT arms were considered for final analysis. The baseline characteristics were comparable in both arms, majority of patients in both arms having stage II disease. For OARs, all dosimetric parameters were significantly better in the IG-IMRT arm. Acute radiation induced toxicities (dermatitis, genito-urinary and gastrointestinal toxicities) were significantly less in the IG-IMRT arm. The local, pelvic, and distant control were comparable in both arms. Based on our experience, the use of IG-IMRT with patient-specific ITV margins results in reduction in acute OAR toxicities in patients without compromising on tumor control. • This randomised study compares 3DCRT with IG-IMRT in locally advanced cervical cancer. • IG-IMRT reduced late OAR toxicities without compromising tumor control. • Median time to develop grade ≥2 late toxicities was prolonged in IG-IMRT arm. • We propose IGRT even in node negative patients as per the availability of resources. [ABSTRACT FROM AUTHOR]

External beam radiotherapy (EBRT) is essential to offer an effective cancer treatment, but it needs to be accessible, well-timed, and high-quality. There is a global lack of radiotherapy infrastructure and investment that compromises the cancer outcomes. The authors aim to quantify the future needs of EBRT until 2040 to cover the future demand. Based on the Global Cancer Observatory estimate for new cancer cases in Portugal for 2040 it was calculated the optimal number of EBRT courses. The OUP is the proportion of new cancer cases that should receive EBRT at least once. In line with the International Atomic Energy Agency (IAEA) DIrectory of RAdiotherapy Centres and European SocieTy for Radiotherapy and Oncology - Health Economics in Radiation Oncology guidelines, we estimated the number of EBRT machines / Megavoltage (MV) units needed. Also, the authors followed the IAEA staffing guidelines. The calculated median increase in the optimal number of EBRT courses for the year 2040 was found to be 18% when compared to the requirements in 2020. The projected number of optimal EBRT courses for 2040 was estimated to be approximately 34.000. Consequently, a range of 18 to 30 new EBRT machines/ MV units will need to be installed to adequately address the growing demand. To meet this demand, it is anticipated that a total of 28 to 46 radiation oncologists, 22 to 36 medical physicists, and 61 to 102 radiation therapists will be required. The deficit of EBRT machines / MV units in Portugal will require a change in the cancer related – policies and an investment to offer full access to EBRT treatments. • Global lack of Radiotherapy infrastructure compromises cancer outcomes. • Authors quantify future EBRT needs in Portugal until 2040. • Authors estimate an 18% increase in optimal EBRT courses by 2040. • Estimated need for 18 to 30 new EBRT machines to meet growing demand. • Urgent policy changes and investment needed to address Portugal's EBRT deficit. [ABSTRACT FROM AUTHOR]

The cerebellum is a key structure in working and procedural memory. The aim of the present prospective exploratory study was to investigate, the metabolic characteristics of the cerebellum in posterior fossa tumor (PFT) survivors using 3D proton magnetic resonance spectroscopy imaging (3D MRSI), to determine whether metabolites could be useful biomarkers of memory impairment. Sixty participants were included in the IMPALA study, divided into three groups: 22 irradiated PFT, 17 nonirradiated PFT, and 21 healthy controls matched with irradiated PFT for age, sex, and handedness. PFT survivors were treated at least 5 years ago, either by surgery or a combination of surgery, chemotherapy, and radiotherapy. All participants underwent working and procedural memory tests and multimodal MRI including a 3D MRSI sequence. N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) metabolite values were extracted from the cerebellum for comparisons between groups, correlations with neurocognitive test scores, and radiotherapy doses. Median (range) age at neurocognitive tests was 18 (7–26) years. Median Cho, Cr, NAA, and Lac values, and the ratio of NAA to the sum of metabolites were significantly lower for PFT survivors than for healthy controls (p < 0.05). Scores on working and procedural memory tests were significantly lower for PFT survivors (p < 0.004) and correlated with median and maximum Cho and NAA values (0.28 < r < 0.49, p < 0.04). Except for creatine, the other metabolites were not significantly different between irradiated and nonirradiated survivors. MRSI values in the cerebellum were not correlated with either total dose or doses received by this structure. Results revealed changes in cerebellar metabolic values in PFT survivors that were closely correlated with memory deficits, suggesting that some metabolites could be used as markers of cognitive decline, but this will require validation on a larger sample size. • 3D MRSI was used to assess metabolic profile of cerebellum in posterior fossa tumor (PFT) survivors. • Cerebellar metabolic values were lower in PFT survivors. • Metabolite values were closely correlated with memory deficits. • Some metabolites could be used as markers of memory impairment. [ABSTRACT FROM AUTHOR]

To assess in patients with 1–10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken. • Changes in clinical practice away from whole brain radiotherapy necessitated early trial closure. • No significant differences in any neurocognitive outcomes were observed. • Compliance with serial neurocognitive function assessments was high. • Patients in the hippocampal sparing arm had significantly less insomnia and drowsiness. [ABSTRACT FROM AUTHOR]

Adjuvant radiation therapy (ART) after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiation therapy that decreased the normal pelvic tissue radiation hazards. However, there are still scarce controlled randomized studies addressing this issue. One hundred thirty-one cystectomized urothelial bladder cancer patients were enrolled; 122 were randomized to receive ART of 50 Gy/25 fractions 4 weeks after cystectomy or cystectomy alone (CY). Sixty-two were included in the ART arm and 60 in the CY arm. Twenty-four ART and 30 CY patients received neoadjuvant chemotherapy. Eleven patients (9%) had cotenant neobladder diversion, 6 in ART, and 5 in CY arms. All ART patients were treated with intensity modulated radiation therapy with daily verification cone beam computed tomography. The median follow-up was 42.7 months. The 3-year adjusted locoregional recurrence–free survival rate was higher in the ART arm, measuring 81% (95% CI, 69%-94%) compared with 71% (95% CI, 60%-80%; p =.0457). ART significantly improved the locoregional relapse–free rate in the cystectomy bed and the pelvic side wall (p =.016 and p =.001, respectively). The overall, event-free, and distant metastasis–free survival did not rank to the level of statistical significance in the 2 arms. Even though the acute side effects were slightly higher in ART, the late toxicities were almost equal in the 2 groups. ART is safe and quite tolerable after radical cystectomy when using precise radiation techniques. These techniques significantly improved the locoregional recurrence–free survival but had insignificant improvement on the overall survival. ART did not affect the distant metastasis–free survival. Similar studies are performed in different centers around the world to confirm the value of ART in urothelial bladder cancer. [ABSTRACT FROM AUTHOR]

Hypoxia in tumors is associated with increased malignancy and resistance to conventional photon radiation therapy. This study investigated the potential of particle therapy to counteract radioresistance in syngeneic rat prostate carcinoma. Subcutaneously transplanted R3327-HI tumors were irradiated with photons or carbon ions under acute hypoxic conditions, induced by clamping the tumor-supplying artery 10 min before and during irradiation. Dose-response curves were determined for the endpoint "local tumor control within 300 days" and compared with previously published data acquired under oxic conditions. Doses at 50% tumor control probability (TCD 50) were used to quantify hypoxia-induced radioresistance relative to that under oxic conditions and also to quantify the increased effectiveness of carbon ions under oxic and hypoxic conditions relative to photons. Compared with those under oxic conditions, TCD 50 values under hypoxic conditions increased by a factor of 1.53 ± 0.08 for photons and by a factor of 1.28 ± 0.06 for carbon ions (oxygen enhancement ratio). Compared with those for photons, TCD 50 values for carbon ions decreased by a factor of 2.08 ± 0.13 under oxic conditions and by a factor of 2.49 ± 0.08 under hypoxic conditions (relative biological effectiveness). While the slope of the photon dose-response curves increased when changing from oxic to hypoxic conditions, the slopes were steeper and remained unchanged for carbon ions. The reduced oxygen enhancement ratio of carbon ions indicated that the required dose increase in hypoxic tumors was 17% lower for carbon ions than for photons. Additionally, carbon ions reduced the effect of intertumor heterogeneity on the radiation response. Therefore, carbon ions may confer a significant advantage for the treatment of hypoxic tumors that are highly resistant to conventional photon radiation therapy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer. In this phase 3, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiation therapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiation therapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiation therapy–induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea, ≥G1 and ≥G2 diarrhea lasting at least 3 days, and damage to the rectal mucosa due to radiation therapy measured by endoscopy. Two hundred and eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 142). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs 14.8 and 4.5 days, respectively; P <.001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs 55.7%, P <.001). Three patients felt intolerable or abdominal pain after rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P =.061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P <.001). The results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating lymphocytes (TILs) have prognostic significance in several cancers, including breast cancer. Despite interest in combining radiation therapy with immunotherapy, little is known about the effect of radiation therapy itself on the tumor-immune microenvironment, including TILs. Here, we interrogated longitudinal dynamics of TILs and systemic lymphocytes in patient samples taken before, during, and after neoadjuvant radiation therapy (NART) from PRADA and Neo-RT breast clinical trials. We manually scored stromal TILs (sTILs) from longitudinal tumor samples using standardized guidelines as well as deep learning–based scores at cell-level (cTIL) and cell- and tissue-level combination analyses (SuperTIL). In parallel, we interrogated absolute lymphocyte counts from routine blood tests at corresponding time points during treatment. Exploratory analyses studied the relationship between TILs and pathologic complete response (pCR) and long-term outcomes. Patients receiving NART experienced a significant and uniform decrease in sTILs that did not recover at the time of surgery (P <.0001). This lymphodepletive effect was also mirrored in peripheral blood. Our SuperTIL deep learning score showed good concordance with manual sTILs and importantly performed comparably to manual scores in predicting pCR from diagnostic biopsies. The analysis suggested an association between baseline sTILs and pCR, as well as sTILs at surgery and relapse, in patients receiving NART. This study provides novel insights into TIL dynamics in the context of NART in breast cancer and demonstrates the potential for artificial intelligence to assist routine pathology. We have identified trends that warrant further interrogation and have a bearing on future radioimmunotherapy trials. [ABSTRACT FROM AUTHOR]

The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT. Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV− patients. The median follow-up was 35.8 months. HIV+ patients were younger (P <.01) and predominantly male (P <.01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P =.007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P =.02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P =.01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women. HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique. [ABSTRACT FROM AUTHOR]

Therapy-related myelodysplastic syndrome (t-MDS) is a rare but potentially fatal adverse event caused by chemotherapy or radiotherapy. We report a case of t-MDS diagnosed 8 months after radiotherapy for recurrent carcinoma of the floor of the mouth and cervical lymph node metastases after surgical treatment. A 74-year-old man visited our department with the chief complaint of pain in the lower part of the tongue. Tumor resection and right radical neck dissection (RND) were performed based on the diagnosis of carcinoma of the floor of the mouth (cT1N2bM0). A computed tomography scan at 10 months postoperatively showed metastatic lymph nodes in the left neck, right hyoid bone, right parotid subpolar, and anterior trachea. Therefore, the patient underwent left RND and excision of the right hyoid bone, subpolar right parotid and anterior tracheal metastatic lymph nodes. Postoperative radiation therapy (70 Gy) was administered to the neck bilaterally. An upper gastrointestinal examination revealed a carcinoma in situ in the lower esophagus, and endoscopic submucosal dissection of the esophagus was performed. He had pancytopenia preoperatively, which progressed postoperatively; therefore, a bone marrow examination was performed to rule out a hematological malignancy. Bone marrow smear and flow cytometric analyses indicated the development of t-MDS. He received supportive transfusion therapy but died 8 months after the diagnosis of t-MDS. During post-treatment follow-up, clinicians should be aware of t-MSD, in addition to cancer recurrence and metastasis. [ABSTRACT FROM AUTHOR]

The delivery of ultra-high dose rates of radiation, called flash irradiation or flash-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of flash-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the flash effect and the ongoing developments to bring this new modality to patient treatment. [ABSTRACT FROM AUTHOR]

Ultra-high dose rate external beam radiotherapy (UHDR-RT) uses dose rates of several tens to thousands of Gy/s, compared with the dose rate of the order of a few Gy/min for conventional radiotherapy techniques, currently used in clinical practice. The use of such dose rate is likely to improve the therapeutic index by obtaining a radiobiological effect, known as the "FLASH" effect. This would maintain tumor control while enhancing tissues protection. To date, this effect has been achieved using beams of electrons, photons, protons, and heavy ions. However, the conditions required to achieve this "FLASH" effect are not well defined, and raise several questions, particularly with regard to the definition of the prescription, including dose fractionation, irradiated volume and the temporal structure of the pulsed beam. In addition, the dose delivered over a very short period induces technical challenges, particularly in terms of detectors, which must be mastered to guarantee safe clinical implementation. IRSN has carried out an in-depth literature review of the UHDR-RT technique, covering various aspects relating to patient radiation protection: the radiobiological mechanisms associated with the FLASH effect, the used temporal structure of the UHDR beams, accelerators and dose control, the properties of detectors to be used with UHDR beams, planning, clinical implementation, and clinical studies already carried out or in progress. [ABSTRACT FROM AUTHOR]

In head and neck squamous cell carcinoma (HNSCC), early complications of the radiotherapy (RT) are observed from the beginning of the treatment to a few months after its end. During external radiotherapy treatment, several patient-dependent parameters can cause a modification of the dose distribution compared to the planned distribution due to variation in patient positioning, anatomy, or intra-fractional movements for example. To verify these parameters during treatment sessions, one of the most commonly used solutions is the cone-beam computed tomography (CBCT). Nowadays, the use of CBCT may constitutes a significant part of the total dose at the end of treatment (up to 10 cGy per session) and more often the volume irradiated by imaging is larger than the one irradiated by the treatment, leading to unintentional irradiation of nearby organs. In this study, we asked whether the imaging low dose added to a following fraction dose (2 Gy) may affect the biological response in terms of DNA repair. Using an IVInomad dosimeter and scintillating fiber probes specially designed for this exploratory study, we exposed fibroblasts cells from head and neck cancer (HNC) patients to a CBCT dose followed by a radiotherapy fraction dose. DNA double strand breaks and DNA repair were assessed by immunofluorescence using the biomarkers gamma H2AX (γH2AX) and pATM. The median dose of CBCT was measured between 17 to 21 mGy per session. The kinetics of both biomarkers were found to be strongly dependent on the individual factor in radiosensitive patients. For HNC patients, a prior CBCT dose applied few minutes before the 2 Gy dose may have a sublinear effect on the DNA repair mechanisms and potentially on observed health tissue toxicity. The preliminary results obtained highlight the importance of individual and tissue factors for recognizing and repairing DSB during a treatment by radiotherapy using CBCT. [ABSTRACT FROM AUTHOR]

Stereotactic radiosurgery (SRS) is an established treatment for intracranial meningioma, yet this approach is often precluded by tumor size or proximity to critical structures. Fractionated radiotherapy (RT) may be employed to address these limitations. We performed a comparison of local control (LC) outcomes between 3 stereotactic techniques. A retrospective review was performed of 543 consecutive patients with 613 histologically-proven World Health Organization grade I or radiographically-defined benign intracranial meningioma treated with SRS (median dose: 1250 cGy) (n = 211), fractionated SRS (2500 cGy in 500 cGy fractions) (n = 170), or conventionally fractionated stereotactic radiotherapy (FSRT) (median dose: 5022 cGy in ≤200 cGy fractions) (n = 232) in the definitive (n = 475) or postoperative (n = 138) setting between January 2008 and December 2021. Postoperative treatment was delivered upfront after a subtotal resection (n = 43) or for recurrent disease (n = 95). Median follow-up per lesion was 8.0 years. LC for all lesions at 5/10/14 years was 97.4%/86.8%/86.8%. Base of skull location (P = 0.01), tumor volume ≥5 cc (P = 0.01), and recurrent disease (P = 0.02) were associated with inferior LC. No difference was observed in LC by fractionation regimen; LC at 5/10 years was 97.3%/85.7% for SRS, 97.5%/89.1% for fractionated SRS, and 97.5%/86.3% for FSRT. Dose escalation above 1250 cGy for SRS or above 5040 cGy for FSRT did not result in improved LC. Durable LC was observed at long-term follow-up of intracranial meningioma treated with stereotactic radiosurgery and RT. LC outcomes were similar across the 3 fractionation regimens, suggesting that clinicians may tailor RT recommendations based on clinical factors without concern for reduced efficacy. [ABSTRACT FROM AUTHOR]

Population-based studies on the cause of readmission within 90 days after surgery or radiotherapy for metastatic spine tumors are scarce. We aimed to investigate the risk factors for readmission within 90 days after initial surgical or radiation treatment for metastatic spine tumors. Patients who were diagnosed with metastatic spine tumors between 2012 and 2019 and underwent spinal magnetic resonance imaging within 1 year were classified according to treatment (surgical or radiotherapy groups), and the causes of the 90-day readmission and patient characteristics were compared. Overall, data from 15,815 patients (surgical group, 13,974 patients; radiotherapy group, 1841 patients) were evaluated. Radiotherapy was preferred in younger and male patients with a high Charlson Comorbidity Index, whereas surgery was mainly performed in patients with lumbar metastasis. Radiotherapy, age of 30–69 years, male sex, and Charlson Comorbidity Index >1 increased the risk of 90-day readmission in patients with metastatic spine tumors. The main causes of 90-day readmission among patients with metastatic spine tumors who received radiotherapy included tumor recurrence, chemotherapy, radiotherapy, and treatment of other organ metastases with radiotherapy. These study findings offer a better understanding of the causes of readmission following radiotherapy or surgical treatment in patients with metastatic spine tumors, and these results can help reduce postoperative morbidity and medical costs among these patients. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592–3864 AUD (£1350–2012 GBP) per patient was estimated had these patients been treated with the protocol. The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol. • Cost per 5-year local control outcome was similar for Stage I-III breast cancer ranging from $29,675 AUD to $32,478 AUD. • Cost per 5-year overall survival outcome was cheaper for stage III breast cancer compared with Stage I-II breast cancer. • Use of the FAST-Forward ultrahypofractionation protocol significantly reduces RT costs. [ABSTRACT FROM AUTHOR]

Tumour response assessments, as per Response Evaluation Criteria in Solid Tumours (RECIST 1.1), are based on the sum of diameters (SODs) of the primary tumour (longest diameter) and/or short axis diameter of lymph nodes. This study evaluates the response categorisation as per RECIST 1.1 vs Computed tomography (CT) based volumetric assessment of RECIST (proposed as vRECIST) in locally advanced head and neck cancers (LAHNCs) undergoing treatment. The pre-treatment SODs and CT estimated tumour volumes were recorded in 45 LAHNCs treated with radiotherapy (RT), chemoradiotherapy (CTRT) or thermochemoradiotherapy (HTCTRT). Tumour responses were assessed independently as per RECIST 1.1 and vRECIST by two radiation oncologists and grouped into complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). These response groups were evaluated for the likely congruence of the two approaches, as categorised independently by these two observers. All patients in stages III (n = 7), IVA (n = 16) and IVB (n = 22) were inoperable and had received either RT alone (n = 1), CTRT (n = 12) or HTCTRT (n = 32). Based on SODs criteria of RECIST 1.1, of the 45 patients, 5 and 40 were grouped as PR and SD by the first observer, while this changed to 34 and 10, respectively and 1 PD, with vRECIST (p < 0.001). Similarly, for the second observer, the 4 PR and 41 SD grouped using RECIST 1.1 were recategorised to 34 PR, 10 SD, and 1 PD by vRECIST (p < 0.001). Thus, a mismatch of 66. 6% and 68. 8%, respectively, was evident by observers first and second in categorising SD based on SODs of RECIST 1.1 vs PR on vRECIST. Treatment responses in LAHNCs assessed using SODs resulted in significant uncertainties and failed to reflect actual volumetric changes in tumours during treatment. It is perhaps time to consider replacing the SODs of RECIST 1.1 with vRECIST for unequivocal tumour response categorisation in the present era of image-based oncology practice. • Tumour responses are assessed on %reduction in the sum of diameters (SODs) as per RECIST 1.1. • Pre- and post-treatment tumour volumes on computed tomography (CT) were evaluated for tumour response. • Gross mismatches in response categories grouped by SOD vs tumour volume were evident. • Revision of tumour response assessment criteria of RECIST 1.1 is strongly desirable. • Suggest to replace SOD with target volume (vRECIST) for tumour response assessments. [ABSTRACT FROM AUTHOR]

To investigate how absorbed doses to mastication structures in modern radiotherapy (RT) technique for head and neck cancer (HNC) compared with earlier RT techniques and with published trismus tolerance doses. To compare the incidence of radiation-induced trismus by earlier and newer RT techniques. This study investigated two HNC patient cohorts treated with RT in 2007–2012 (three-dimensional conformal radiotherapy [3DCRT] and/or intensity-modulated radiotherapy [IMRT]; n =121 [ Cohort 1 ]) and 2017–2020 (volumetric-modulated arc therapy [VMAT]; n =124 [ Cohort 2 ]). All patients underwent RT without mastication structure–sparing intent, had normal mouth-opening ability before RT, and were prospectively assessed. Trismus was defined as the maximal interincisal opening ≤35 mm at any follow-up (3-, 6-, and 12-months post-RT). The temporomandibular joints (TMJs), masseter, and medial/lateral pterygoid muscles were delineated on the planning CT:s. Mean doses were compared between cohorts, and evaluated with respect to published trismus tolerance doses. P values ≤ 0.05 indicated statistical significance. Within 12 months post RT, 74/121 (61%) of patients in Cohort 1 had experienced trismus compared to 11/124 (9%) in Cohort 2. Averaged mean doses (±S.D.) for the masseter muscles were 35.2±8.3 Gy in Cohort 1 and 20.2±8.7 Gy in Cohort 2 (P <0.001). Corresponding numbers were 19.1±16.2 and 4.3±4.3 Gy for the TMJs, 53.7±10.1 and 40.2±16.8 Gy for the medial pterygoid muscles, and 29.2±18.7 and 9.2±8.4 Gy for the lateral pterygoid muscles (all P <0.001). Masseter muscle doses were below tolerance doses in 23% of patients in Cohort 1 compared with 90% in Cohort 2. The corresponding numbers were 52% and 96% for the TMJs, 8% and 36% for the medial pterygoid muscles and 72% and 100% for the lateral pterygoid muscles. Mastication structure mean doses by more recent RT techniques were generally below proposed tolerance doses, with dose reductions of 10–20 Gy compared with earlier techniques. Modern RT without mastication-structure-sparing intent resulted in below 10% of HNC patients experiencing trismus compared with 60% treated with earlier techniques. • Modern radiotherapy can substantially spare organs-at-risk in head and neck cancer. • Mastication-structure mean radiation doses were reduced by 10–20 Gy. • These dose reductions were accompanied by a trismus reduction from 60% to 10%. [ABSTRACT FROM AUTHOR]

To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29–92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gy α/β:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1–2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials. • One of the few prospective SRS studies exploring MTD across different clinical settings. • 34 Gy, 32 Gy, and 24 Gy single fraction were safely delivered to lung, liver, bone. • The highest dose level was reached in all the settings, not exceeding the MTD. • The toxicity profile was low with one acute and five late toxicities >G2. • High LC rates and encouraging long-term outcomes were observed. [ABSTRACT FROM AUTHOR]

This paper examines the integration of artificial intelligence (AI) in radiotherapy for cancer treatment. The importance of radiotherapy in cancer management and its time-intensive planning process make AI adoption appealing especially with the escalating demand for radiotherapy. This review highlights the efficacy of AI across medical domains, where it surpasses human capabilities in areas such as cardiology and dermatology. Focusing on radiotherapy, the paper details AI's applications in target segmentation, dose optimization, and outcome prediction. It discusses adaptive radiotherapy's benefits and AI's potential to enhance patient outcomes with much improved treatment accuracy. The paper explores ethical concerns, including data privacy and bias, stressing the need for robust guidelines. Educating healthcare professionals and patients about AI's role is crucial as it acknowledges potential job-role changes and concerns about patients' trust in the use of AI. Overall, the integration of AI in radiotherapy holds transformative potential in streamlining processes, improving outcomes, and reducing costs. AI's potential to reduce healthcare costs underscores its significance with impactful change globally. However, successful implementation hinges on addressing ethical and logistical challenges and fostering collaboration among healthcare professionals and patient population data sets for its optimal utilization. Rigorous education, collaborative efforts, and global data sharing will be the compass guiding its' success in radiotherapy and healthcare. [ABSTRACT FROM AUTHOR]

To (i) determine the actual radiotherapy utilization (RTU) stratified by age, (ii) develop an age- and co-morbidity adjusted optimal RTU model and (iii) examine the tolerance and toxicity of treatment of older patients with head and neck cancer. A retrospective cohort study based on New South Wales Cancer Registry records (2010–2014) linked to radiotherapy data (2010–2015) and admitted patient data (2008–2015) for patients diagnosed with head and neck cancer. We calculated the actual RTU, defined as the proportion of patients who received at least one course of radiotherapy within a year of diagnosis, by age group, including patients aged 80+ years. We also calculated the age and comorbidity-adjusted optimal RTU. For treatment tolerance, the radiotherapy dose for each age group and the completion rate for a seven week 70 Gray (Gy) course of curative intent radiotherapy were computed. The number of emergency department (ED) presentations were used as a surrogate measure of acute treatment toxicity for patients receiving 70 Gy. Of the 5966 patients diagnosed with head and neck cancer, 814 (13.6%) were aged 80+ years. For all age groups, the actual RTU was less than the optimal RTU. The age- and comorbidity-adjusted optimal RTU for patients aged 80+ was 52% (95% CI: 51%–53%), and the actual RTU was 40% (95% CI: 37%–44%). Only 4.4% of patients aged 80+ received 70 Gy, and the completion rate for a 70 Gy course of radiotherapy for these patients was 92%. The ED presentation rate was similar for all age groups. The actual RTU was less in the 80+ years patients and across all age groups. Fewer patients in the 80+ group received curative intent schedules compared to the actual RTU rate for younger age groups, despite similar rates of completion of curative intent radiotherapy and acute toxicity. • This population-based research highlights that even after adjusting for comorbidities, with increasing age, the actual radiotherapy utilisation rate (RTU) is less than the optimal RTU for patients with head and neck cancer. • The age- and comorbidity-adjusted optimal RTU rates for patients aged 80+ years using the cancer specific C3 'all sites' comorbidity index was 52% (95% CI: 50%–52%) and the actual RTU was 40% (95% CI: 37%–44%). • The completion rate and acute toxicity of a 70 Gy radiotherapy course were similar in all age groups. This suggests good treatment tolerance in carefully selected cases. • Further work, however, is required for the older cohort of patients to determine the reasons for the lower receipt of curative intent schedules and for all age groups, reasons for the underutilisation of RT. [ABSTRACT FROM AUTHOR]

NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug–drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug–radiotherapy combinations. [ABSTRACT FROM AUTHOR]

In inflammatory breast cancer, radiation therapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiation therapy modalities on the risk of loco-regional and distant relapse. This retrospective multicenter study included patients with localized inflammatory breast cancer treated between 2010 and 2017. Standard postmastectomy radiation therapy consisted of daily fractions to a total dose of 50 Gy equivalent without a boost or bolus, while intensified radiation therapy referred to the use of a boost or bolus. The cumulative incidence curves of locoregional and distant recurrence were displayed using the competing risk method. Of the 241 included patients, 165 were treated with standard and 76 with intensified radiation therapy. There was significantly more nodal involvement in the intensified group. With a median follow-up of 40 months postradiation therapy, there was no difference between standard versus intensified radiation therapy regarding the cumulative incidence of locoregional (P =.68) or distant recurrence (P =.29). At 5 years, the risks of locoregional and distant recurrence were 12.1% (95% CI, 7.5; 17.7) and 29.4% (95% CI, 21.8; 37.3) for patients treated with standard radiation therapy and 10.4% (95% CI, 4.4; 19.3) and 21.4% (95% CI, 12.6; 31.9) for those treated with intensified radiation therapy. In multivariate analyses, triple-negative subtype and absence of complete pathologic response were associated with a higher risk of loco-regional recurrence. Radiation therapy intensification had no significant impact on locoregional and distant recurrence. For patients with a non-complete pathologic response (n = 172, 71.7%), no significant differences were observed between the 2 groups for loco-regional (P =.80) and distant (P =.39) recurrence. Severe toxicity rates were similar in both groups. Contrary to other important series, this large retrospective multicentric study did not show a locoregional or distant control benefit of intensified radiation therapy. Pooled prospective studies and meta-analyses of intensified radiation therapy are warranted to endorse this approach. [ABSTRACT FROM AUTHOR]

Only a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that stereotactic ablative radiation therapy of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and secondarily explore the efficacy of stereotactic irradiation for lung volume reduction (SILVR) over 18 months after intervention in patients with severe emphysema. We conducted a single-arm, prospective clinical trial in eligible patients with severe emphysema treated with unilateral stereotactic ablative radiation therapy (45 Gy in 3 fractions) to a target within the most emphysematous region. The primary outcome was safety in terms of incidence of grade ≥3 adverse events, and the secondary outcome was efficacy. Eight patients received the intervention. Median (range) baseline characteristics were age 73 years (63-78); forced expiratory volume in 1 second percent of predicted value (FEV 1 %) 28.5% (19.0-42.0); diffusing capacity of the lungs for carbon monoxide percent of predicted value 40% (24.0-67.0); and body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index 5.5 (5-9). The incidence of grade ≥3 adverse events was 3 of 8 (37.5%). The relative change in target lobe volume was –23.1% (–1.6 to –41.5) and –26.5% (–20.6 to –40.8) at 6 and 18 months, respectively. The absolute ΔFEV 1 % was greater in patients with a BODE index ≤5 versus ≥6 (+12.0% vs –2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V 60BED3) correlated with the absolute change in target lobe volume at 18 months. SILVR appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe and effective in patients with a lower BODE index and/or less parenchymal destruction. [ABSTRACT FROM AUTHOR]

There is limited clinical data for recommendations on how to deliver thoracic radiation therapy (TRT) concurrently with chemotherapy in limited-stage small cell lung cancer. We reviewed radiation therapy treatment plans in a randomized phase 2 trial comparing high-dose with standard-dose twice-daily TRT to assess treatment planning techniques, dose-volume data for target volumes and organs at risk (OARs), evaluate compliance with the protocol, associations with radiation-induced toxicity, and whether an imbalance in treatment planning parameters might be a reason for the large survival benefit of the higher dose (median overall survival 43.6 vs 22.6 months). In the study, 170 patients were to receive 4 courses of platinum/etoposide and were randomized to receive twice-daily TRT of 60 Gy/40 fractions (fx) or 45 Gy/30 fx. TRT treatment plans for those who received 1 or more fx of TRT (n = 166) were analyzed. The most common treatment planning technique was 3-dimensional conformal radiation therapy (67%). The 75th percentile of the reported dose-volume parameters for the OARs were within the protocol-recommended limits for both groups. Mean doses to the esophagus of 25.5 Gy (IQR, 20.2-31.3; 60 Gy/40 fx) and 24.3 Gy (IQR, 20.3-27.5; 45 Gy/30 fx) were associated with 21% and 18% ≥ grade 3 acute esophagitis, respectively. In the 60 Gy/40 fx group, a mean dose to the lungs of 16.5 Gy (IQR, 15.8-16.9), V20 Gy of 29.5% (IQR, 28.8-30.4), and V5 Gy of 65.6% (IQR, 61.5-68.7) led to ≥ grade 3 pneumonitis in 4% of the patients. There was no ≥ grade 3 pneumonitis in the 45 Gy/30 fx group. The treatment planning techniques, the percentage change in volumes between original and redelineated OARs, planning target volumes, relative doses, and laterality were well balanced between the randomly assigned groups. Considering the incidences of severe radiation-induced toxicities were within the range of other recent trials, the reported doses to the OARs appear to be safe. Treatment planning parameters were well balanced between the randomly assigned groups, supporting that the survival benefit of the twice-daily 60 Gy/40 fx TRT schedule was due to the higher dose. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors, in particular those treated with radiation therapy, are at high risk of long-term iatrogenic events. The prediction of risk of such events is mainly based on the knowledge of the radiation dose received to healthy organs and tissues during treatment of childhood cancer diagnosed decades ago. We aimed to set up a standardized organ dose table to help former patients and clinicians in charge of long-term follow-up clinics. We performed whole body dosimetric reconstruction for 2646 patients from 12 European countries treated between 1941 and 2006 (median, 1976). Most plannings were 2- or 3-dimensional. A total of 46% of patients were treated using Cobalt 60, and 41%, using a linear accelerator. The median prescribed dose was 27.2 Gy (IQ1-IQ3, 17.6-40.0 Gy). A patient-specific voxel-based anthropomorphic phantom with more than 200 anatomic structures or substructures delineated as a surrogate of each subject's anatomy was used. The radiation therapy was simulated with a treatment planning system based on available treatment information. The radiation dose received by any organ of the body was estimated by extending the treatment planning system dose calculation to the whole body, by type and localization of childhood cancer. The integral dose and normal tissue doses to most of the 23 considered organs increased between the 1950s and 1970s and decreased or plateaued thereafter. Whatever the organ considered, the type of childhood cancer explained most of the variability in organ dose. The country of treatment explained only a small part of the variability. The detailed dose estimates provide very useful information for former patients or clinicians who have only limited knowledge about radiation therapy protocols or techniques, but who know the type and site of childhood cancer, sex, age, and year of treatment. This will allow better prediction of the long-term risk of iatrogenic events and better referral to long-term follow-up clinics. [ABSTRACT FROM AUTHOR]