Radiotherapy Schedules Research Articles

Nivolumab and hypofractionated radiotherapy in patients with advanced melanoma: A phase 2 trial.

Radiotherapy is thought to enhance anti-tumor immunity, particularly when delivered in a hypofractionated and multisite manner. Therefore, we investigated the effects of combining radiotherapy with nivolumab in patients with advanced melanoma. This was a multicenter, non-randomized, phase 2 trial that enrolled patients with treatment-naïve metastatic melanoma. They received nivolumab (240 mg / 2 weeks) plus radiotherapy (day 15, 6 Gy × 3). When feasible, one target from each organ was irradiated (no irradiation of all targets). The primary endpoint was 1-year overall survival (OS). This trial included 64 patients between March 2017 and July 2019. The median follow-up was 23.5 (2.3-43.8) months. The median age was 68 (35-95) years, patients were mostly male (67 %) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 (72 %), stage IV-M1c disease (47 %), and were BRAF-wild-type (67 %). The 2-year OS and 1-year PFS rates were 65.2 % and 56 %, respectively (P = 0.22 and P = 0.03, vs. 58 % and 43 %, respectively, in the Checkmate 066 study). Thirty-seven (58 %) and twenty-seven (42 %) patients were irradiated at one and multiple targets, respectively. The ECOG-PS (1 vs. 0; HR = 3.5; P = 0.005) was an independent prognostic factor for OS. Irradiating more than one site and irradiating a smaller cumulative tumor volume tended to correlate with better outcome. Grade 3-4 treatment-related adverse events occurred in 21.9 % of the patients (no grade 5). Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results.

A critical review of randomized controlled trials on topical corticosteroids for the prevention of radiation dermatitis in breast cancer.

Topical steroids have shown effectiveness in preventing radiation dermatitis (RD) in breast cancer patients in randomized controlled trials (RCTs). This review provides an in-depth analysis of the study methodology of these RCTs to review whether topical steroids should be employed in routine clinical practice. A systematic literature search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was conducted from database inception until May 31, 2024. RCTs comparing topical steroids with moisturizers or placebo for the prophylaxis of RD in breast cancer patients were included. The methodology of the RCTs, including how topical steroids were applied, whether crossover in the control arm was allowed, if stratification factors were employed, and the reporting of side effects was evaluated. Twelve RCTs met inclusion criteria. Four different topical steroids were used, including betamethasone 0.1%, mometasone 0.1%, hydrocortisone 1%, and beclomethasone. Eleven studies (92%) showed that topical steroids were effective in reducing incidence or delaying occurrence of grade 2 or above RD with a relative risk of 0.69 (range, 0.19 to 0.98). In all RCTs, topical steroids were consistently used from the start of radiotherapy (RT) until completion to 3weeks post-RT. Five RCTs (42%) provided patient education on topical steroid application. Six (50%) reported on subsequent management if moist desquamation occurred. Four studies (33%) stratified potential risk factors of RD during randomization. No studies reported any long-term side effects of topical steroids. Topical steroids are effective in reducing the incidence of RD. However, heterogeneity was observed among the RCTs with regard to how and when the topical steroids were applied. The long-term safety profile of topical steroids is not well studied. In the context of modern radiotherapy planning techniques and increased use of hypofractionation radiation schedules, a repeat RCT addressing these methodological concerns may provide more guidance to clinicians.

The interplay between acute and late toxicity among patients receiving prostate radiotherapy: an individual patient data meta-analysis of six randomised trials.

The association between acute and late toxicity following prostate radiotherapy has not been well studied using data from multiple randomised clinical trials and fractionation schedules. We aimed to characterise the relationship between acute and late genitourinary and gastrointestinal toxicity among patients receiving conventionally fractionated or moderately hypofractionated prostate radiotherapy. This was an individual patient data meta-analysis that identified randomised phase 3 trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium that had individual-level acute and late toxicity data available and were available before Dec 1, 2023. Trials without individual patient data were excluded. Data were provided to MARCAP by study investigators. The associations between acute (≤3 months after radiotherapy) and late (>3 months after radiotherapy) grade 2 or greater genitourinary and gastrointestinal toxicities were assessed using adjusted generalised linear mixed models (adjusted for age, androgen deprivation therapy status, type of radiotherapy, radiation dose, and radiation schedule). In the subset of trials that collected Expanded Prostate Cancer Index Composite quality of life (QOL) evaluations, the association between acute genitourinary and gastrointestinal toxicity and decrements at least twice the minimal clinically important difference (MCID) for urinary and bowel QOL were also evaluated. Six of 26 available trials met all the eligibility criteria. 6593 patients were included (conventionally fractionated: n=4248; moderately hypofractionated: n=2345). Median follow-up was 72 months (IQR 61-94). Acute grade 2 or greater genitourinary toxicity was associated with both late grade 2 or greater genitourinary toxicity (odds ratio 2·20 [95% CI 1·88-2·57], p<0·0001) and decrement at least twice the MCID in urinary QOL (1·41 [1·17-1·68], p=0·0002). Acute grade 2 or greater gastrointestinal toxicity was associated with both late grade 2 or greater gastrointestinal toxicity (2·53 [2·07-3·08], p<0·0001) and decrement at least twice the MCID in bowel QOL (1·52 [1·26-1·83], p<0·0001). Acute toxicity following prostate radiotherapy was statistically significantly associated with late toxicity and with decrement in patient-reported QOL metrics. These data support efforts to evaluate whether interventions that reduce acute toxicity ultimately reduce the risk of late toxicity. National Institutes of Health and US Department of Defense.

Review of presentations and radiotherapy outcomes of patients with malignant spinal cord compression

Background: Malignant spinal cord compression (MSCC) is the commonest radiotherapy emergency. A high index of suspicion, prompt diagnosis, early referral and treatment is important to restore quality of life and improve survival in patients with MSCC.Aim: This study aimed to evaluate the clinical and treatment characteristics of patients presenting with MSCC at the Radiation Oncology department.Setting: The study was conducted at Steve Biko Academic Hospital, Radiation Oncology.Methods: This is a retrospective review of 110 patients who were treated for MSCC between January 2022 and November 2023. Information on patients’ characteristics, disease characteristics, imaging findings, radiotherapy dose prescription, clinical response and survival was extracted from clinical records.Results: Breast and prostate cancer were the most frequent primary disease sites. Most patients presented in a poor Eastern Cooperative Oncology Group (ECOG) performance status (PS 4), de novo disease (63%) and multilevel vertebral involvement (70%). Eighty-four patients (76.4%) received a single fraction treatment (6 Gy – 8 Gy). The median overall survival was 145 days. Patients with a Rades score of 32–37 points had a statistically significant better overall survival at 1 year compared with those with a score of 22–31 points. There was no difference in survival between single versus multiple fraction treatment.Conclusion: A single fraction radiotherapy schedule is acceptable in this setting where most patients present with extensive disease and non-ambulatory baseline function.Contribution: The findings from this study could be used to establish protocols for treatment strategies in facilities with limited resources.

Optimizing Radiotherapy Timing for Nasopharyngeal Carcinoma: The Impact of Radiation Scheduling on Survival.

Chronoradiobiology has emerged as a potential field of study with therapeutic implications for cancer treatment. We aimed to investigate the association between radiation chronotherapy and the efficacy and toxicity of patients with nasopharyngeal carcinoma (NPC). Patients with nonmetastatic NPC treated with intensity-modulated radiotherapy in Fujian Cancer Hospital between January 2017 and December 2019 were included. Propensity score matching (PSM) with 1:1:1 was used to account for selection bias. Cox regression analysis was performed to explore the impact of radiotherapy timing on patient survival. Sensitivity analysis was implemented to determine the size and directional stability. One thousand forty patients met study inclusion criteria and 332 patients were included in a PSM cohort. In the unmatched cohort analysis, morning radiotherapy exhibited a significantly superior overall survival (OS) outcome (hazard ratio [HR], 0.60 [95% CI, 0.40 to 0.91], adjusted log-rank P = .028) than the afternoon one. After PSM analysis, it was observed that individuals undergoing radiotherapy in the afternoon group (HR, 5.88 [95% CI, 2.55 to 13.58], adjusted log-rank P = .004) and the night group (HR, 4.81 [95% CI, 1.91 to 12.11], adjusted log-rank P = .018) displayed a tendency toward shorter OS compared with the morning group. No significant differences in acute treatment-related adverse effects were observed among the three groups. Morning radiotherapy demonstrated consistent robustness in the multivariable analysis, thereby establishing an association with higher OS. The directionality of the effect size was consistent across sensitivity analysis. These results underscore the potential benefits of scheduling radiotherapy in the morning for NPC management, although prospective studies are needed to confirm these findings.

Ladies project: large database in endometrial cancers for a personalized treatment.

To compare Italian use with current international guidelines and to evaluate oncological outcomes and toxicity patterns of adjuvant radiation therapy (RT) for endometrial cancer (EC) in Italian women. To conduct a retrospective multicentre Italian study a large database was set up. Inclusion criteria were: accrual between 2010 and 2020, treatment with surgery, post-operative external beam RT (EBRT) and/or interventional radiotherapy (IRT) associated or not with adjuvant chemotherapy. Oncological outcomes, acute and late toxicities were analysed according to RT schedule and risk group. A total of 1848 patients, from 16 Italian RT centres were enrolled (median age 65 years, range 27-88). All patients received post-operative RT associated with chemotherapy in 31%. Patients were stratified on the basis of standard risk factors (Bosse et al. in Eur J Cancer 51:1742-50, 2015). After merging intermediate and high-intermediate risk classes into one intermediate group and including advanced and oligometastatic disease in the high-risk group, the low-risk group encompassed 124 patients, the intermediate-risk 1140, and the high risk 576. No low-risk patient developed local relapse (LR). Multivariate analysis showed that intermediate risk patients had a 2.5-fold increased risk of LR if treated with IRT alone vs EBRT-IRT boost. RT schedule did not impact significantly on LR in high risk patients. All acute toxicity parameters were highest in patients who received EBRT with simultaneous integrated boost (EBRT-SIB) and lowest in patients who received only IRT (p < 0.0001). Late toxicity was highest patients who received EBRT-SIB and lowest in those who were given EBRT with sequential boost (p < 0.0001). This retrospective study showed that Italian administration of adjuvant RT for EC is in accordance with current international guidelines. IRT alone for low-risk patients and EBRT associated with vaginal IRT remain standard adjuvant approaches for EC.

Mathematical modeling predicts optimal immune checkpoint inhibitor and radiotherapy combinations and timing of administration.

Radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) therapy has attracted substantial attention due to its potential to improve outcomes for patients with several types of cancer. However, the optimal administration timepoints and drug combinations remain unclear because the mechanisms underlying RT-induced changes in immune checkpoint molecule expression and interaction with their ligand(s) remain unclear. Herein, we demonstrated the dynamics of lymphocyte-mediated molecular interactions in tissue samples from esophageal cancer patients throughout RT schedules. Single-cell RNA-sequencing and spatial transcriptomic analyses were performed to investigate the dynamics of these interactions. The biological signal in lymphocytes transitioned from innate to adaptive immune reaction, with increases in ligand-receptor interactions, such as PD-1-PD-L1, CTLA4-CD80/86, and TIGIT-PVR interactions. A mathematical model was constructed to predict the efficacy of five types of ICI when administered at four different timepoints. The model suggested that concurrent anti-PD-1/PD-L1 therapy or concurrent/adjuvant anti-CTLA-4/TIGIT therapy would exert a maximal effect with RT. This study provides rationale for clinical trials of RT combined with defined ICI therapy, and these findings will support future studies to search for more effective targets and timing of therapy administration.

Modeling the Acute Mucosal Toxicity of Fractionated Radiotherapy Combined with the ATM Inhibitor WSD0628.

Ataxia Telangiectasia-mutated (ATM) inhibitors are being developed as radiosensitizers to improve the antitumor effects of radiotherapy, but ATM inhibition can also radiosensitize normal tissues. Therefore, understanding the elevated risk of normal tissue toxicities is critical for radiosensitizer development. This study focused on modeling the relationship between acute mucosal toxicity, radiation dose, fractionation schedule, and radiosensitizer exposure. The ATM inhibitor WSD0628 was combined with single or fractionated doses of radiation delivered to the oral cavity or esophagus of Friend Leukemia virus B (FVB) mice. The potentiation by WSD0628 was quantified by a sensitizer enhancement ratio (SER), which describes the changes in radiation tolerance for radiation combined with WSD0628 relative to radiation-only regimens. WSD0628 profoundly enhanced radiation-induced acute oral and esophageal toxicities. For oral mucosal toxicity, the enhancement by WSD0628 with 3 fractions of radiation resulted in an SER ranging from 1.3 (0.25 mg/kg) to 3.1 (7.5 mg/kg). For the 7.5 mg/kg combination, the SER increased with increasing number of fractions from 2.2 (1 fraction) to 4.3 (7 fractions) for oral toxicity and from 2.2 (1 fraction) to 3.6 (3 fractions) for esophageal toxicity, which reflects a loss of the normal tissue sparing benefit of fractionated radiation. These findings were used to develop a modified biologically effective dose model to determine alternative radiation schedules with or without WSD0628 that result in similar levels of toxicity. Successful radiosensitizer dose escalation to a maximally effective therapeutic dose will require careful deliberation of tumor site and reduction of radiation dose volume limits for organs at risk.

SMILE—stereotactic multiple fraction radiotherapy for non-spine bone metastases: study protocol for a multicenter, open-label phase III randomized controlled trial

BackgroundThe SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions.MethodsThis international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information.DiscussionIf the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology.Trial registrationThe trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022.

CTIM-16. SAFETY AND PRELIMINARY EFFICACY OF AZD1390 + RADIATION THERAPY FOR GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma is an aggressive cancer; intensity-modulated radiation therapy (IMRT) with concomitant and adjuvant temozolomide is the first-line standard of care. AZD1390, an ataxia telangiectasia mutated kinase inhibitor, aims to augment the efficacy of IMRT without exacerbating neurotoxicity. AZD1390 is optimized for blood–brain barrier penetration, confirmed in healthy volunteers (NCT03215381) and patients with glioblastoma (Phase 0; NCT05182905). This Phase 1, open-label study (NCT03423628) evaluated safety and efficacy of AZD1390 and IMRT in patients with glioblastoma. METHODS Adult patients received escalating once-daily AZD1390 doses with IMRT 35 Gy in 10 fractions over 2 weeks (Arm A, recurrent glioblastoma) or IMRT 60 Gy in 30 fractions over 6 weeks (Arm C, newly-diagnosed O-6-methylguanine-DNA methyltransferase unmethylated glioblastoma). Patients received 2 additional weeks of adjuvant AZD1390 post-IMRT. Primary objective was safety; secondary objectives included efficacy and pharmacokinetics. RESULTS As of Feb 6, 2024, 115 patients (Arm A=75; Arm C=40) received AZD1390 10–900 mg/day. Pharmacokinetics were linear, with a slightly more-than dose-proportional increase and mean elimination half-life ~9–11 hours. Most patients had ≥1 treatment-emergent adverse event (AE), most commonly fatigue (51.3%), nausea (39.1%) and headache (38.3%). Grade ≥3 AZD1390-related AEs occurred in 18/115 patients. The maximum tolerated dose was 400 mg (Arm A) and 300 mg (Arm C). Dose-limiting toxicities included creatinine kinase elevation (Arm A) and radiation skin injury (Arm C). AEs led to AZD1390 discontinuation in 15/115 patients. Safety profiles were mostly consistent across Arms despite different radiation schedules. At target-engaging doses, median overall survival was 12.7 months (95% CI: 10.7–18.9; Arm A) and still maturing (Arm C). CONCLUSIONS Concurrent AZD1390 and IMRT demonstrated manageable safety at doses with known target engagement. Preliminary efficacy is encouraging (Arm A). AZD1390 can potentially act as a radiosensitizer for glioblastoma treatment. Clinical investigation is ongoing.

RADT-31. EMBRACING HYPOFRACTIONATED RADIOTHERAPY FOR GLIOBLASTOMA IN A RESOURCE CONSTRAINED SETTING

Abstract BACKGROUND Various hypofractionated schedules of radiation have been tried in glioblastoma with limited success. Though the shorter fractionation is appealing and there is evidence (since 2017) to use the 40Gy in 15 fractions regime in the elderly, the fear of toxicity limits its use, especially in the developing nations. We have tried this regime in younger patients (not eligible for supportive care alone) who had a poor Performance status or if only a biopsy had been performed. METHODS 25 patients treated for glioblastoma from 2017 to 2023 using 4000cGy delivered in 15 fractions were included in the study. The patient details were obtained retrospectively from the medical records and the Eclipse Treatment Planning system. RESULTS There were 16 males and 9 females. Median age was 62 years (range 52 to 77 years). 56% of the patients had an ECOG performance score of 3; and the rest 2. 12 lesions were on the Right side, 9 in the left and the rest extended across the midline. Surgery was limited to biopsy alone in 8; almost as many (n=7) had a Near Total Resection; the rest underwent decompression. Surprisingly, almost half the patients were MGMT unmethylated. 16 patients were on steroids either during or after radiation. All 25 maintained their Performance Status and completed radiation as planned. The mean GTV Volume - 53.48 cc (Range 6-201). Dmax was never above 103%; Brainstem and Optic Apparatus Dmax were also kept below 100%. In the majority, 3 beams of mixed energy were used. 19 patients received both Concurrent and adjuvant temozolomide; only adjuvant was given to 6. The median overall survival was 7.7 months (range 2-60.6 months) and the Disease free survival was 7.5 months (Range 1-60.5 months). CONCLUSIONS Hypofractionated radiotherapy of 4000 cGy in 15 fractions seems to be a kinder treatment in glioblastoma patients with a poor performance status.

Once-a-Week Ablative Radiotherapy as Replacement of Prolonged Fractionation in Frail Patients: Feasibility and Toxicity Results

Introduction The aim of this work was to explore the use of an original once-weekly radiotherapy fractionation in elderly or frail patients with recurrence or metastasis from different solid malignancies. Material and Methods A retrospective analysis was conducted on 29 patients treated from 2011 to 2019 with a once-weekly radiotherapy schedule. Patients received a median dose of 27.5 Gy, with weekly fractions of 4-5 Gy over 7-10 weeks. The treatment aimed at both palliative and cytoreductive objectives. Primary endpoints were feasibility and compliance, secondary outcome was acute toxicity. Results All patients completed the planned radiotherapy without interruptions. Acute toxicity was mild, with only one patient developing grade 3 toxicity (bowel perforation). Three months post-treatment, 74% of patients experienced symptom relief and tumor response. One-year local control rates were 26.7%, and treatment was generally well-tolerated. Conclusion This once-weekly hypofractionated radiotherapy regimen demonstrated feasibility, good tolerance, and promising tumor response in frail and elderly patients. Although limited by a small sample size, the approach offers a practical alternative for patients unable to undergo conventional daily radiotherapy. Further studies on larger cohorts are required to validate these findings.

Current Radiotherapy Management of Extensive-Stage Small-Cell Lung Cancer in the Immunotherapy Era: An Italian National Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients.

Subclinical cardiac damage monitoring in breast cancer patients treated with an anthracycline-based chemotherapy receiving left-sided breast radiation therapy: subgroup analysis from a phase 3 trial.

This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT). Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software. In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5Gy; for patients with subclinical heart damage, the mean MHD was 1.6Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage. Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events.

Cancer Patients' Views on Ultrahypofractionated Radiotherapy: A Questionnaire-Based Survey.

Ultrahypofractionated (UHF) radiotherapy provides several treatment schedules, including five fractions per week (5/5-UHF), three fractions per week (3/5-UHF), and one fraction per week (1/5-UHF). This study aimed to assess patient preferences for these UHFradiotherapy schedules and offer insights to support patient-centered radiotherapy. A questionnaire survey was conducted among cancer patients who had received at least 10 fractions of definitive or palliative radiotherapy, delivered on consecutive weekdays at our institution. The survey was administered during the final week of treatment and included four questions regarding the patients' living conditions and seven questions about their perceptions of radiotherapy, including preferences for UHFradiotherapy schedules. Between April and July 2023, 71 eligible patients completed the questionnaire. The mean age was 65.2 years; 48 patients (68%) were male, and 36 patients (51%) were inpatients. Thirty-one patients (44%) traveled more than one hour to the hospital, and 34 patients (47%) reported stress from daily hospital visits for radiotherapy. In response to the question, "If you were to receive 5-fraction radiotherapy, would you choose 5/5-UHF, 3/5-UHF, or 1/5-UHF?" 64 patients responded. Among these, 27 (42%) chose 5/5-UHF, 19 (30%) chose 3/5-UHF, and 18 (28%) chose 1/5-UHF. Regarding the question, "Which is more important: a shorter treatment period with the same fractionation or reduced fractionation with the same treatment period?" 31 patients (48%) prioritized shorter treatment periods, while 12 (19%) preferred reduced fractionation. Although approximately half of the patients expressed distress from consecutive days of radiotherapy, the shortest treatment period was generally preferred, even if it involved consecutive sessions. The 1/5-UHF radiotherapy schedule was particularly popular among younger male patients, those with longer travel times, and those working full-time. These findings suggest that tailoring radiotherapy schedules to patients' social circumstances may enhance overall satisfaction with treatment.

Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma

Objective The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. Methods A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. Results Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, p < .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. Conclusion Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.

Exploring the feasibility of preoperative tumor-bed boost, oncoplastic surgery, and adjuvant radiotherapy schedule in early-stage breast cancer: A phase II clinical trial.

Oncoplastic breast-conserving surgery (OBCS) improves satisfaction in patients who would fare otherwise sub-optimal cosmetic outcome, while brings challenge in tumor-bed identification during adjuvant radiotherapy. The ultra-hypofractionated breast radiotherapy further shortens treatment sessions from moderately hypofractionated regimens. To circumscribe the difficulty in tumor-bed contouring and the additional toxicity from larger boost volumes, we propose to move forward the boost session preoperatively from the adjuvant radiation part. Thus, the present study aims to evaluate the feasibility of a new treatment paradigm of preoperative primary-tumor boost before breast-conserving surgery (BCS) or OBCS followed by adjuvant ultra-hypofractionated whole-breast irradiation (u-WBRT) for patients with early-stage breast cancer. There was a phase II study. Patients younger than 55 years old, with a biopsy confirmed mono-centric breast cancer, without lymph node involvement were enrolled. Preoperative primary-tumor boost was given by a single 10Gy in 1 fraction, and BCS or OBCS was conducted within two weeks afterwards. Adjuvant u-WBRT (26Gy/5.2Gy/5f) was given in 6 weeks postoperatively without any boost, after the full recovery from surgery. Surgical complications and patient-reported outcomes, as assessed via Breast-Q questionnaires, were documented. A propensity score matching approach was employed to identify a control group at a 1:1 ratio for BREAST-Q outcomes comparison. From May 2022 to September 2023, 36 patients were prospectively enrolled. Surgical complications were observed in 7 cases (19.4%), including 3 cases with Clavien-Dindo (CD) grade 1-2 and 4 cases with CD grade 3 complications. All but four patients (11.1%) started the planned u-WBRT within one week after the pre-defined due dates postoperatively (≤49d). Four patients (11.1%) developed grade 2 radiodermatitis after chemotherapy initiation. Compared to the study group, the control patients reported higher scores in chest physical well-being (P=0.045) and in their attitudes towards arm swelling (P=0.01). No significant difference was detected in the other of domains (Satisfaction with Breasts, Sexual and Psychosocial Well-Being, and Adverse Effects of Radiation). With a median follow-up period of 9.8 months (2.4-18.9mo), none had any sign of relapse. This Phase II clinical trial confirmed the technical and safety feasibility of novel radiation schedule in patients undergoing BCS or OBCS. According to the BREAST-Q questionnaire, patients who underwent novel radiation schedules reported lower satisfaction in chest physical well-being. A randomized controlled trial is necessary to further investigate these findings. Additionally, long-term follow-up is required to assess oncological outcomes.

Choosing Wisely Between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients.

This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules. This multi-institutional retrospective study included patients aged ≥65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established. A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3-149.9), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: HR 1.52, p<0.001; CFRT+TMZ vs. radiotherapy alone: HR 2.52, p<0.001). In a combined analysis with the NOA-08 and NORDIC trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770). CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

Palliative Thoracic Radiotherapy in the Era of Modern Cancer Care for NSCLC.

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher radiation doses administered over longer periods have shown modest survival benefits. These findings stem from studies conducted before the advent of immunotherapy and targeted therapy in clinical practice. Currently, there are no large prospective studies specifically dedicated to palliative radiotherapy conducted in this new treatment era. Modern radiotherapy technologies are now widely available and are increasingly used for palliative purposes in selected patients, reflecting the expanded array of therapeutic options for disseminated NSCLC and improved prognosis. Some traditional tenets of palliative thoracic radiotherapy, such as the improvement of overall survival with a protracted radiation schedule and the use of simple, cost-effective radiation techniques for palliative purposes, may no longer hold true for patients receiving immunotherapy or targeted therapy. The application of IMRT or SBRT in the context of palliative radiotherapy for NSCLC is not yet sufficiently explored, and this is addressed in this review. Moreover, new risks associated with combining palliative radiotherapy with these systemic treatments are being explored and are discussed within the context of palliative care. The optimal timing, doses, fractionation schedules, and treatment volumes for radiotherapy combined with immunotherapy or targeted therapy are currently subjects of investigation. In emergencies, radiotherapy should be used as a life-saving measure without delay. However, for other indications of palliative thoracic radiotherapy, decisions regarding doses, timing relative to systemic treatments, and treatment volumes should be made in a multidisciplinary context, considering the patient's prognosis, anticipated outcomes, and access to potentially effective treatments. We still lack robust data from prospective studies on this matter. This review examines and discusses available evidence on the use of palliative thoracic radiotherapy within the framework of modern treatment strategies for NSCLC.

Long-term Results of Hypofractionated Radiotherapy With Intra-prostatic Boosts in Men With Intermediate- and High-risk Prostate Cancer: A Phase II Trial

AimsIn the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. Material and methodsBIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). Results61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. ConclusionFocal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. ClinicalTrials.gov identifierNCT02125175.