Radiation Therapy Oncology Group Grade Research Articles

CSMed® wound dressing for prophylaxis and management of radiation dermatitis in breast and head–neck cancer patients: a single hospital prospective clinical trial

PurposeCSMed® wound dressing, a dressing with various herb extracts, was tested for its therapeutic effect in radiation dermatitis of breast and head-and-neck cancer patients.MethodsThis study included 20 breast cancer patients and 10 head-and-neck cancer patients. Half of the irradiated area was covered with CSMed® and the other half was under routine treatment. The severity of radiation dermatitis was evaluated with radiation therapy oncology group (RTOG) grade throughout the treatment and the follow-up period. The RTOG grade between the dressed and undressed area were compared to illustrate the therapeutic effect of CSMed® dressing.ResultsThe results showed that CSMed® dressed area had significant lower RTOG score at 3–7 weeks and final record during the treatment, and 1–3 weeks during follow-up than undressed area.ConclusionsThis indicated that CSMed® can delay the onset, reduce the severity, and enhance healing of radiation dermatitis. CSMed® can be used for prophylaxis and management of radiation dermatitis.

Does use of apalutamide enhance outcomes in combination with radiotherapy in metastatic hormone-sensitive prostate cancer? A real-world experience from the UK.

73 Background: Management of metastatic prostate cancer has undergone a significant change over the past decade, with the introduction of several novel agents and repurposing of others. Latest update from STAMPEDE trials shown prostate radiotherapy (RT) improves OS, without detriment in QoL in metastatic home sensitive prostate cancer mHSPC along with Docetaxel in those with low volume metastatic disease. There is no published data on impact of radiotherapy to prostate on Apalutamide treated mHSPC patients. Here we report our real-world experience of Apalutamide in mHSPC with radiotherapy. Methods: Patients with mHSPC (N = 266) from 5 UK centres, were treated with Apalutamide (240 mg) and ADT along with radiotherapy to prostate as per treating clinician’s discretion. The primary endpoint was objective rate (ORR) as determined by patients achieving a PSA decline of ≥90% (PSA90) and ≥50% (PSA50) and secondary endpoints included biochemical progression free survival (bPFS) and safety. Results: The median age for the whole cohort was 73.4 years (interquartile range 52 - 91), A total of 11.6% had received prior radical treatment (prostatectomy or radiotherapy for localised disease) and 88.4% had de novo metastatic disease. Median baseline PSA was 47 ng/ml (range 0.4-17100). The proportion of patients PSA90 and PSA50 at 3, 6 and 12 months is shown in the Table. Median PSA nadir was 0.1 ng/ml(rage 0.01- 48.2) and median time to reach nadir was 6 months (range 3-24 months). 13.5% (35) patients were treated with radiotherapy (RT) after at least 3 months (range 3 -6 months) of starting apalutamide. Patients received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) of radiotherapy (68 % vs 32%). Higher number of patients in RT group had achieved PSA90 compared to no radiotherapy cohort (97.14 % vs 87.3%, p =0.15). Patients treated with RT had median post treatment of PSA 0.01 ng/ml compared to 0.1 ng/ml in non RT group (p=0.0062). After median follow up of 8.4 months, proportion of patients shown biochemical progression in RT vs non RT group were 5.7 % vs 15 % respectively (p= 0.04). Patients with de novo metastatic disease have shown poor PSA response and higher chance of progression compared to patients who had initial radical treatment. Radiotherapy was well tolerated, with 17 % adverse events (Radiation Therapy Oncology Group grade 3–4) reported in radiotherapy group. Conclusions: Early experience of using apalutamide and radiotherapy in mHSPC showed improved PSA response and delayed progression. Treatment was well tolerated. Further follow up and clinical trials are needed to understand the impact on overall survival. [Table: see text]

Dose-Escalated Preoperative Proton Therapy for Retroperitoneal Sarcomas: Initial Outcomes of a New Treatment Paradigm

Retroperitoneal sarcomas (RPS) have varied treatment practices with regard to the use of radiation therapy (RT). Preoperative RT ∼50 Gy is commonly used, but the Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma (STRASS-1) randomized trial demonstrated no improvement in abdominal recurrence-free survival with preoperative RT. Dose escalation has been proposed to improve the efficacy of preoperative RT. We analyzed RPS treated with preoperative intensity modulated proton therapy (IMPT) to an escalated dose of 63 Gy at a single institution. Patients who received preoperative RT with IMPT with RPS between January 2015 and October 2021 were reviewed. IMPT 63 Gy in 28 fractions to the clinical target volume high-risk and 50.4 Gy in 28 fractions to clinical target volume low-risk was used. Patient baseline characteristics, RT dose parameters, toxicities, margin status, and recurrence patterns were recorded. Local control was computed by Fine-Gray analysis and overall survival by Kaplan-Meier analysis. Sixteen patients met the study criteria (n = 16): 12 primary and 4 isolated local recurrences. Median age was 62 years (IQR, 43.5-66 years) and 62.5% were male; 10 were liposarcoma. The median maximum tumor diameter was 19.9 cm (IQR, 12-24 cm). With a median follow-up of 18 months (IQR, 11.5-37 months), the estimated 3-year freedom from local failure rate was 68.2% (95% CI, 41.7%-94.7%); 3-year overall survival (OS) rate was 68.8% (95% CI, 41.9%-95.8%). No Radiation Therapy Oncology Group grade ≥3 acute or late toxicities were noted. In our RPS cohort, preoperative dose-escalated RT to 63 Gy demonstrated comparable local control without G3 acute toxicities. Given the high local recurrence rates of RPS, this approach warrants further study to validate these results and identify patients most likely to benefit from therapy.

Comparison of Acute Gastrointestinal Toxicity of Intensity-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiotherapy in Patients of Carcinoma Cervix.

Introduction Cervical cancer is the most common gynaecological malignancy worldwide, with a higher prevalence in middle- and low-income countries. Chemoradiotherapy, followed by intracavitary brachytherapy, is the treatment of choice in locally advanced cervical cancer. The most common acute side effect of external beam radiotherapy (EBRT) is bowel toxicity in the form of diarrhoea and abdominal cramps. The treatment techniques of EBRT were revolutionised with the advent of intensity modulation. This study aims to prospectively analyse whether the dosimetric advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3DCRT) is translated clinically into a decrease in acute toxicity. Method Twenty-four patients were randomised into two groups: the 3DCRT and the IMRT. Acute gastrointestinal (GI) toxicity was assessed during treatment using radiation therapy oncology group grading. The factors under consideration were age, stage of the disease, treatment technique, chemotherapy, and the intention of therapy (radical or adjuvant). The mean bowel bag dose of the two techniques was analysed. Result Among the factors under consideration, it was found that the treatment technique was the only factor that had a significant association with acute bowel toxicity in both univariate (p = 0.036) and multivariate analyses (p = 0.028). The mean V25 (the volume receiving 25 Gy), V45, and V50 of the bowel bag in the IMRT arm were significantly less than the 3DCRT arm. Grades 2 and 3 acute bowel toxicities were also higher in the 3DCRT arm. Conclusion The treatment technique is essential to determining acute GI toxicity during pelvic radiotherapy. With IMRT, the dose to the bowel bag and, in turn, the acute bowel toxicity can be reduced.

A novel, multi-active emollient for the prevention of acute radiation dermatitis in breast cancer patients: a randomized clinical trial.

To investigate the efficacy of a novel, multi-active emollient in preventing and managing acute radiation dermatitis (ARD) in breast cancer patients undergoing moderate hypofractionated (HF) radiotherapy (RT) compared to standard of care. A monocentric, open-label, randomized clinical trial (RCT) with breast cancer patients receiving moderate HF (dose: 40.05-55.86Gy, fractions: 15-21) was conducted between January 2022 and May 2023. The experimental group received the novel emollient, while the control group received the standard skin care. Patients applied the skin care products twice daily during the complete RT course. The primary outcome was the severity of ARD at the final RT session measured by the modified Radiation Therapy Oncology Group (RTOG) criteria. Secondary outcomes included patient symptoms, quality of life (QoL), and treatment satisfaction. A total of 100 patients with 50 patients per group were enrolled. In the control group, 50% of the patients developed RTOG grade 1 ARD and 48% grade 2 or higher, while in the experimental group, the severity of ARD was significantly lower with 82% grade 1 and 16% grade 2 ARD (P = .013, χ2-test). The frequency and severity of xerosis were significantly lower in the experimental compared to the control group (Ps ≤ .036, Mann Whiney U test). The impact of ARD on the QoL was low, and treatment satisfaction was high in both groups, with no significant difference. This RCT shows that the novel, multi-active emollient significantly reduced the ARD RTOG grade. Research in a more diverse patient population is warranted. ClinicalTrials.gov: NCT04929808 (11/06/2021).

A Phase 2 Trial of Efficacy and Safety of Intraoperative Radiation Therapy for Locally Advanced Laryngocarcinoma

For locally advanced laryngeal cancer (LAL), the local recurrence rate remains 19-40% after radical surgery with postoperative radiotherapy alone or with concurrent chemoradiotherapy in patients with unfavorable prognostic factors. We evaluate local control and acute toxicity of intraoperative radiation therapy (IORT) as a tumor bed boost for locally advanced laryngeal cancer in this prospective phase 2 trial. This phase II clinical study in which a total of 63 LAL patients (T2N1-3/T3N0-3/T4N0-3) were selected and received IORT (T2: 8-10Gy, T3,4:12-15 Gy) as a tumor bed boost during radical surgery, then received external-beam radiation therapy (EBRT) at a total dose of 54-60Gy within 6 weeks after surgery, 5 times per week, 1.8-2Gy per time, 30 times in total. The median follow-up time was 20 months (7 -39 months). The primary outcome was the local control (LC) and 2 - year survival rate determined using the Kaplan-Meier method. This study is registered with ClinicalTrials.gov, NCT04278638. A total of 63 patients consented to participate in the study; 59 males and 4 females, median age was 61 years (40-81 years), 14 patients had supraglottic LAL, 44 patients had glottic LAL and 5 patients had subglottic LAL. 10 patients showed high differentiation and 44 patients showed moderate differentiation and 9 patients showed low differentiation with laryngeal squamous cell carcinoma. 3 patients were in T2N1-2 stage, 40 patients in T3N0-2 stage, and 20 patients in T4N0-2 stage, 48 patients received total laryngectomy and 15 patients received hemilaryngectomy; 16 patients were lymph node-positive and 1 patient developed vascular tumor thrombus after surgery. After surgery combined with IORT and EBRT, the 1- and 2- year LC rates were 98.2% and 93.1 %, respectively, 2-year overall survival rate was 97.4%. Pharyngeal fistula was observed in 1 patient (1. 6 %) and wound infection in 3 patients (4.8%). Radiation Therapy Oncology Group (RTOG) grade 3 pain and RTOG grade 4 dyspnea were noted in one patient (1.6%) and 2 patients (3.2 %), respectively. In summary, our prospective phase II trial proved that the addition of intraoperative radiotherapy as a tumor bed boost to postoperative radiotherapy provided local therapeutic benefit to patients with locally advanced laryngeal cancer. Our data support the safety of this combined therapy. Additional investigation is warranted to determine the role of intraoperative radiotherapy in the local treatment of locally advanced laryngeal cancer.

Skin Microbiome Composition is Associated with Radiation Dermatitis in Breast Cancer Patients Undergoing Radiation after Reconstructive Surgery: A Prospective, Longitudinal Study

Approximately 95% of breast cancer (BC) patients receiving radiotherapy (RT) develop varying degrees of radiation dermatitis (RD), which can greatly affect the patient's quality of life and aesthetics. Severe acute RD can lead to interruption or delay of RT. Currently, there is no consensus on the prevention and management of RD. The skin microbiota (SM), which are mainly composed of bacteria and fungi, are essential for skin homeostasis and microbial dysbiosis is correlated with the onset and progression of many common skin diseases. However, to date, research on the role of the SM in RD remains scarce. This prospective, longitudinal study aims to analyze the association of SM with RD. We collected 200 SM samples both before and after RT from the region in the irradiated chest wall of 100 BC patients receiving RT after reconstructive surgery and samples from the corresponding region in the contralateral breast for bacterial 16S and fungal ITS (internal transcribed spacer) rRNA sequencing. Acute RD was graded according to the Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG). Patients were divided into no or mild dermatitis (N/MD, RTOG grade 0 or 1) and severe dermatitis (SD, RTOG grade 2 and above). The compositional differences across groups were compared using STAMP and high-dimensional class comparisons by linear discriminant analysis of effect size (LEfSe). Differences in metabolic function between groups were predicted by the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) method. Significant differences were observed in the diversity and composition of the SM between N/MD and SD both before and after RT. Analysis of bacterial 16S sequencing (n = 89, 63 N/MD, 26 SD) showed significantly higher relative abundance of particular taxa such as Ralstonia, Truepera, Methyloversatilis genera and lower abundance of particular taxa including Staphylococcus, Corynebacterium genera in N/MD patients. Besides, analysis of fungal ITS sequencing (n = 71, 53 N/MD, 18 SD) showed significantly higher relative abundance of particular taxa such as Hypocreaceae family and lower abundance of particular taxa such as Sporidiobolus genus in N/MD patients. Pathways including fatty acid synthesis were predicted to be enriched in N/MD patients. The SM and pathway markers were identified in this study to be associated with the severity of acute RD in BC patients undergoing RT after reconstructive surgery. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level.

Intensity-Modulated Radiation Therapy Alone Versus Intensity-Modulated Radiation Therapy and Brachytherapy for Early-Stage Oropharyngeal Cancers: Results From a Randomized Controlled Trial

The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC). This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival. Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24). The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.

Natural and miscellaneous agents for the prevention of acute radiation dermatitis: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the available literature describing the efficacy of natural and miscellaneous agents in preventing acute radiation dermatitis (RD) in cancer patients. OVID MedLine, Embase, and Cochrane literature databases were searched from 1946 to January 2023 for randomized controlled trials studying the use of natural and miscellaneous agents to prevent RD. RevMan 5.4 was used for the meta-analysis to calculate the pooled effect sizes and 95% confidence intervals (CI) using the random effects analysis. For the systematic review and meta-analysis, 19 and 16 studies were included, respectively. Of the five studied natural products (aloe vera, oral enzymes, olive oil, calendula, and curcumin), only oral enzymes and olive oil significantly reduced the incidence of Radiation Therapy Oncology Group grade 2+ (RR: 0.42, 95%CI 0.30-0.58, p < 0.00001, RR: 0.66, 95% CI 0.51-0.85, p = 0.001, resp.). The oral enzymes also reduced the grade 3+ RD incidence (RR: 0.18, 95%CI 0.06-0.55, p = 0.003). The other agents demonstrated no significant effect. This review and meta-analysis on natural and miscellaneous agents in preventing RD in cancer patients demonstrated that oral enzymes and olive oil prevented RD severity. However, evidence supporting natural agents to prevent RD is inconsistent, mainly because of low studies numbers, low-quality study designs, and small sample sizes. Therefore, concrete conclusions cannot be made. Research on (new) natural or miscellaneous agents should focus on a randomized controlled double-blinded study design with a large patient population, a higher consistency in research methods, and clinician- and patient-reported outcomes.

A dose escalated fiducial marker-based image guided radical radiotherapy in locally advanced prostate cancers: A single institute experience from India

Image guided radiotherapy (IGRT) is one of the most commonly used treatment in LAPC. Dose escalation >74 Gy has shown to improve the biochemical control and freedom from failure rate in LAPC.We started treating LAPC patients with dose escalated IGRT in our institute since 2008. We did a retrospective analysis to see the biochemical relapse-free survival, cancer-specific survival, and bladder and rectal toxicity. A total of 50 consecutive prostate cancer patients were treated with dose escalated IGRT between January 2008 to Dec 2013. Out of these, 37 patients of LAPC were analyzed and their medical records were retrieved. All were biopsy proven adenocarcinoma of prostate with D'Amico high risk category (PSA >20 ng/mL or Gleason score (GS) >7 or T2c-T4). Three gold fiducial markers were placed in the prostate. Patients were immobilized in supine position with either ankle or knee rest. Partial bladder filling and rectum emptying protocol was followed. Clinical target volume (CTV) segmentation was done according to EORTC recommendation. Population based PTV expansion from CTV of 10 mm (cranio-caudal), 10 mm (medio-lateral), 10 mm (anterior) and 5 mm (posterior) was given. In patients with radiologically enlarged pelvic lymph node, whole pelvis intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy/28# followed by prostatic boost 26Gy/13# by IMRT using image guidance. Rest of the patients received prostate only RT to a dose of 76Gy/38# by IGRT. Daily On board KV images were taken and 2D-2D fiducial marker matching was done and shifts were applied on machine before treatment. Biochemical relapse was defined as per Phoenix definition (nadir + 2 ng/mL). Radiation Therapy Oncology Group (RTOG) toxicity grading system was used to document acute and late toxicity. Median age of patients was 66 years. Median pre-treatment PSA was 22 ng/mL. Thirty patients (81%) had T3/T4 lesions and nodal metastasis was seen in 11 (30%). Median GS was 8. Median radiotherapy dose was 76 Gy. Imaging before radiation delivery was done in 19(51%) patients and 100% in 14 (38%) patients. With a median follow up of 6.5 years, 5-year biochemical relapse-free survival (bRFS) and cancer-specific survival (CSS) was 66% and 79% respectively. Mean bRFS and CSS were 71 months and 83 months however Median bRFS and CSS were not reached. Distant metastasis was seen in 8 (22%). RTOG grade III bladder and rectal toxicity was seen in 2 (6%) and 2 (6%) patients respectively. Dose escalated IGRT with fiducial marker positional verification for LAPC is doable in Indian setup provided more emphasis given on daily on-board imaging with rigorous bladder filling and rectal emptying protocol. Long term follow up is needed to assess the effect on distant disease-free survival and CSS.

Palliative radiation therapy as a treatment for feline urinary bladder masses in four cats.

Urinary bladder masses in four cats were treated with palliative radiation therapy (RT). Three cats were previously diagnosed with chronic kidney disease (CKD): International Renal Interest Society (IRIS) stage 2 in two cats and IRIS stage 3 in one cat. One cat had a diagnosis of hyperthyroidism and inflammatory bowel disease. Three cats had urinary tract infections diagnosed by urine culture and susceptibility testing prior to or during treatment. All patients had urine cytospin cytology performed; one case showed suspect urothelial carcinoma and three had no cytological evidence of neoplasia. All clients declined further sampling from the bladder masses. Therefore, cytologic/histologic diagnosis in all cases was not available. An abdominal ultrasound was performed in all cats, which revealed urinary bladder mass(es) prior to referral for RT. Three cats had pretreatment thoracic radiographs, which revealed no evidence of pulmonary metastasis. An abdominal CT was performed in all cases and one case had thoracic CT performed for staging. The thoracic CT showed a focal lesion of unknown etiology in the right caudal lung lobe. Palliative RT was performed with four weekly 6 Gy fractions (24 Gy in total). The urinary signs in all cats resolved over the course of RT: after the first RT treatment in two cats and after the second RT treatment in two cats. There were two Veterinary Radiation Therapy Oncology Group grade 1 gastrointestinal and one grade 2 genitourinary acute RT side effects. This is the first report in the literature of a standardized RT protocol as a treatment option for feline urinary bladder masses.

Efficacy of topical steroids in preventing radiation dermatitis: A systematic review and meta-analysis.

To evaluate the relative efficacy of topical steroids in preventing radiation dermatitis (RD). Multiple databases including Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Biological Medicine (SinoMed), and Wanfang Database were searched for randomized controlled trials (RCTs) of RD prevention in patients with cancer from inception to November 26, 2021, followed by an update on June 1, 2021. Six RCTs evaluating the efficacy of topical steroids in preventing RD in a total of 661 patients with cancer were included. RD incidence was lower with topical steroids compared with placebo at week 3 (relative risk [RR]=0.68, 95% confidence interval [CI]: 0.31-1.50) and at radiation therapy (RT) completion (RR=0.97, 95% CI: 0.93-1.00). Topical steroids demonstrated a less risk of developing dermatitis of Radiation Therapy Oncology Group (RTOG) grades 2 and 3 at the completion of RT (RR=0.66, 95% CI: 0.55-0.80 and RR=0.54, 95% CI: 0.38-0.77, respectively). However, topical steroids did not reduce RTOG grades 1 and 2 dermatitis at week 3(RR=0.73, 95% CI: 0.45-1.14 and RR=0.66, 95% CI: 0.27-1.60, respectively). Notably, the use of topical steroids did not decrease RD incidence when patients received combined chemotherapy (RR=0.60, 95% CI: 0.42-0.86), and an obvious reduction in the incidence of RD at RT completion was found when patients used the topical steroids twice-daily (RR=0.66, 95% CI: 0.47-0.93, P=0.02). Topical steroids reduced RD incidence in patients receiving RT. Thus, twice-daily topical steroids may be recommended for patients at the beginning of RT.

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial.

Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. Accuray.

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: 5-Year Efficacy and Toxicity in the DELINEATE Trial

Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy. DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years. Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C). The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.

Application and clinical efficacy of Sufu medical chitosan hydrogel dressing in radiation skin damage caused by radiotherapy for cervical cancer.

To investigate the benefits of Sufu medical chitosan hydrogel dressing(Sufu) in the prevention and control of radiation skin damage during radiotherapy for cervical cancer as a combined modality. Ninety-seven cervical cancer patients who underwent radiotherapy at the Cancer Hospital of China Medical University between May 2017 and November 2018 were recruited according to given inclusion and exclusion criteria. The patients were assigned to a control group (n=48, washing the perineal area with normal saline) and an observation group (n=49, application of Sufu onto the site of radiotherapy in addition to washing the perineal area with normal saline). The treatment regimens for the two groups continued until the end of radiotherapy. A comparison of the RTOG (Radiation Therapy Oncology Group) grading of acute radiation-induced skin reactions (ARISRs), pain intensity (measured by the verbal rating scale (VRS)) and post-treatment wound healing was drawn between the two groups. In the observation group, 81.6% (40/49) of the patients had radiation dermatitis, which was significantly lower than the incidence rate (95.8%, 46/48) in the control group (P <0.05). The observation group was at higher risk of radiation dermatitis when given a high radiation dose, while the control group was more likely to have radiation dermatitis when administered with a moderate radiation dose (P <0.05). The median time of occurrence of pain and the median time of onset of skin reactions were significantly later in the observation group as compared with the control group (P <0.05, respectively). In the observation group, the pain relief rate was 92.50% at Day-3, and the wound healing rate was 95.0% at Day-7, significantly higher than in the control group (73.9% and 80.4%) (P <0.05, respectively). During radiotherapy for cervical cancer, Sufu can effectively prevent and control radiation-induced skin and mucous membrane damage, delay the onset of radiation dermatitis and substantially reduce the incidence rate, relieve radiation dermatitis and pain and promote wound healing.

Radiation Therapy Dose Escalation in Unresectable Ewing Sarcoma: Final Results of a Phase 3 Randomized Controlled Trial

Our aim was to assess the effect of radiation therapy (RT) dose escalation on outcomes in surgically unresectable Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET). Patients with nonmetastatic unresectable ES/PNET (excluding intracranial/chest wall) receiving vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide chemotherapy, planned for definitive RT, were accrued in this single-institution, open-label, phase 3 randomized controlled trial. Randomization was between standard dose RT (SDRT; 55.8 Gy/31 fractions/5 days a week) versus escalated dose RT (EDRT; 70.2 Gy/39 fractions/5 days a week) with a primary objective of improving local control (LC) by 17% (65%-82%). Secondary outcomes included disease-free survival (DFS), overall survival (OS), and functional outcomes by Musculoskeletal Tumor Society score. Between April 2005 and December 2015, 95 patients (SDRT 47 and EDRT 48) with a median age of 17 years (interquartile range, 13-23 years) were accrued. The majority of patients were male (59%). Pelvis was the most common site of primary disease (n=60; 63%). The median largest tumor dimension (9.7 cm) and the median maximum standardized uptake value (8.2) on pretreatment fluorodeoxyglucosepositron emission tomography-computed tomography were similar. At a median follow-up of 67 months, the 5-year LC, DFS, and OS for the entire cohort was 62.4%, 41.3%, and 51.9%, respectively. The 5-year LC was significantly better in EDRT compared with SDRT (76.4% vs 49.4%; P=.02). The differences in DFS and OS at 5 years (for EDRT vs SDRT) did not achieve statistical significance (DFS 46.7% vs 31.8%; P=.22 and OS 58.8% vs 45.4%; P=.08). There was a higher incidence of Radiation Therapy Oncology Group grade >2 skin toxic effects (acute) in the EDRT arm (10.4% vs 2.1%; P=.08) with excellent functional outcomes (median Musculoskeletal Tumor Society score=29) in both arms. EDRT results in improved LC with good functional outcomes without a significant increase in toxic effects. Radiation dose escalation should be considered for surgically unresectable nonmetastatic ES/PNET.

Linac-based hypofractionated stereotactic radiotherapy for metastases involving the brainstem

The long-term efficacy and complications of hypofractionated stereotactic radiotherapy (hSRT) to metastases involving the brainstem are not well reported. Our objective is to review the results of metastases intrinsic to or abutting the brainstem treatedwith hSRT.Patients treated with hSRT in 5 fractions at our institution from 2016 to 2020 were retrospectively reviewed. Varian Eclipse v13.7 TPS was used for treatment planning. MRI images were fused with CT images acquired at the time of simulation, and contoured structures include the brainstem, the GTV, and a 2 mm margin was used to generate the PTV. MR imaging was performed at 3-month intervals. Survival was assessed at the last available follow-up; tumor control was assessed at 6 and 12 months and toxicity was assessed based on the Radiation Therapy Oncology Group grading system at regular follow-up. Twenty patients were treated with 5 fraction treatment dose plans ranging from 20 Gy − 31.25 Gy. GTV mean volume was 3.5 cc ± 4.3 cc (range 0.1 cc – 18.9 cc). The median overall survival was 6.5 months (range: 1 to 29 months). The twelve-month tumor control rate was 80%. Toxicity was generally mild, with only one patient demonstrating Grade 3 toxicity. Two patients had radiographic progression, but neither required surgical intervention. In our series, hSRT resulted in similar rates of survival, tumor control, and toxicity as compared with published single fraction series. Dose escalation of lesions adjacent to the brainstem can be considered and maybe more feasible with a hypofractionated regimen of 5 fractions.

Surface Dose Measurements in Chest Wall Postmastectomy Radiotherapy to Achieve Optimal Dose Delivery with 6 MV Photon Beam.

Aim:A tissue-equivalent bolus of sufficient thickness is used to overcome build up effect to the chest wall region of postmastectomy radiotherapy (PMRT) patients with tangential technique till Radiation Therapy Oncology Group (RTOG) Grade 2 (dry desquamation) skin reaction is observed. The aim of this study is to optimize surface dose delivered to chest wall in three-dimensional radiotherapy using EBT3 film.Materials and Methods:Measurements were conducted with calibrated EBT3 films with thorax phantom under “open beam, Superflab gel (0.5 cm) and brass bolus conditions to check correlation against TPS planned doses. Eighty-two patients who received 50 Gy in 25# were randomly assigned to Group A (Superflab 0.5 cm gel bolus for first 15 fractions followed by no bolus in remaining 10 fractions), Group B or Group C (Superflab 0.5 cm gel or single layer brass bolus, respectively, till reaching RTOG Grade 2 skin toxicity).Results:Phantom measured and TPS calculated surface doses were within − 5.5%, 4.7%, and 8.6% under open beam, 0.5 cm gel, and single layer of brass bolus applications, respectively. The overall surface doses (OSD) were 80.1% ±2.9% (n = 28), 92.6% ±4.6% (n = 28), and 87.4% ±4.7% (n = 26) in Group A, B, and C, respectively. At the end of treatment, 7 out of 28; 13 out of 28; and 9 out of 26 patients developed Grade 2 skin toxicity having the OSD value of 83.0% ±1.6% (n = 7); 93.7% ±3.2% (n = 13); and 89.9% ±5.6% (n = 9) in Groups A, B, and C, respectively. At the 20th–23rd fraction, 2 out of 7; 6 out of 13; and 4 out of 9 patients in Groups A, B, and C developed a Grade 2 skin toxicity, while the remaining patients in each group developed at the end of treatment.Conclusions:Our objective to estimate the occurrence of optimal dose limit for bolus applications in PMRT could be achieved using clinical EBT3 film dosimetry. This study ensured correct dose to scar area to protect cosmetic effects. This may also serve as quality assurance on optimal dose delivery for expected local control in these patients.

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer

AimsThe safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup. Materials and methodsIn total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35–37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria. ResultsForty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively. ConclusionSBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a).

Outcomes and Tolerability of Definitive and Preoperative Chemoradiation in Elderly Patients With Esophageal Cancer: A Retrospective Institutional Review

PurposeOur purpose was to report outcomes of elderly patients who underwent definitive treatment involving radiation therapy for esophageal cancer at our institution. Methods and MaterialsWe performed a retrospective review of patients aged ≥75 years with esophageal cancer treated with definitive radiation therapy (≥45 Gy) at our institution from 1997 to 2019. Acute and late Radiation Therapy Oncology Group grade 3+ toxicities were recorded. Survival was estimated using the Kaplan-Meier method. ResultsOf the 89 patients included, median age was 80 and 78% were male. Median adjusted Charlson Comorbidity Index and Karnofsky Performance Status were 5 (3-12) and 80 (50-100), respectively. The majority of cancers were adenocarcinoma (58%), distal (67%), and stage III (62%). Fifty-eight percent underwent definitive chemoradiotherapy, and one-third underwent preoperative intent chemoradiotherapy. Median prescribed dose was 50 Gy (45-66 Gy), and intensity modulated radiation therapy was used in 76%. Eighty-five percent completed the radiation therapy course. Among these, 20% had radiation therapy breaks. For those receiving concurrent chemotherapy, 37% had a dose reduction and 39.5% had a break/cycle reduction. Acute grade 3+ toxicity was 22%, with 2% grade 5 toxicity. Twenty-one of the 29 patients (72%) treated with preoperative intent underwent surgery. There were no deaths 90 days postoperatively. For patients who underwent surgery, 1- and 2-year overall survival were 95% and 84%. For those who did not undergo surgery, 1- and 2-year overall survival were 70% and 52%. ConclusionsThere is a role for aggressive radiation therapy in well-selected elderly patients with esophageal cancer. However, optimization of supportive care, chemotherapy regimens, radiation therapy dose/fractionation, and surgical indications are needed to reduce toxicity.