Radiation Therapy Oncology Group Toxicity Research Articles

Stereotactic body radiotherapy with CyberKnife® System for low- and intermediate-risk prostate cancer: clinical outcomes and toxicities of CyPro Trial.

Stereotactic body radiotherapy (SBRT) of 35-36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low-intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups. Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial. A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months. The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3-4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant. Our study confirms that SBRT of 35-36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low-intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.

Salvage Radiation Therapy After Radical Prostatectomy: Analysis of Toxicity by Dose-Fractionation in the RADICALS-RT Trial

Emerging data indicate comparable disease control and toxicity of normal postoperative fractionation and moderate hypofractionation radiation therapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66 Gy in 33 fractions (f) over 6.5 weeks or 52.5 Gy in 20 f over 4 weeks. This non-randomized, exploratory analysis explored the toxicity of these 2 schedules in patients who had adjuvant RT. Information on RT dose was collected in all patients. The Radiation Therapy Oncology Group toxicity score was recorded every 4 months for 2 years, every 6 months until 5 years, then annually until 15 years. Patient-reported data were collected at baseline and at 1, 5, and 10 years using standard measures, including the Vaizey fecal incontinence score (bowel) and the International Continence Society Male Short-Form questionnaire (urinary incontinence). The highest event grade was recorded within the first 2 years and beyond 2 years and compared between treatment groups using the χ² test. Of 634 patients, 217 (34%) were planned for 52.5 Gy/20f and 417 (66%) for 66 Gy/33f. In the first 2 years, grade 1 to 2 cystitis was reported more frequently among the 66 Gy/33f group (52.5 Gy/20f: 20% vs 66 Gy/33f: 30%; P=.04). After 2 years, grade 1 to 2 cystitis was reported in 16% in the 66-Gy group and 9% in the 52.5-Gy group (P=.08). Other toxic effects were similar in the 2 groups, and very few patients had any grade 3 to 4 toxic effects. Patients reported slightly higher urinary and fecal incontinence scores at 1 year than at baseline, but no clinically meaningful differences were reported between the 52.5 Gy/20f and 66 Gy/33f groups. Patient-reported health was similar at baseline and at 1 year and similar between the 52.5 Gy/20f and 66 Gy/33f groups. Severe toxic effects were rare after prostate bed radiation therapy with either 52.5 Gy/20f or 66 Gy/33f. Only modest differences were recorded in toxic effects or in patient-reported outcomes between these 2 schedules.

Superficial kilovoltage x-ray radiotherapy for the treatment of cutaneous mast cell tumors on the head in three dogs and one cat: a limited retrospective case series.

To report preliminary findings of hypofractionated superficial radiotherapy for treatment of cutaneous mast cell tumors (MCTs) and report the acute and late toxicity associated with its use. 3 dogs and 1 cat. In this retrospective study, medical records from January 2021 through July 2022 were searched for animals that received superficial radiation therapy for MCTs of the head. 4 patients with 5 MCTs were included. Three of the masses were periocular and required protection of the globe with a tungsten eye shield. One patient did not complete the intended protocol due to diffuse metastatic spread noted after the second fraction. Of the 3 patients that completed their protocol, 100% had a complete response. Two canine patients were treated adjunctively with toceranib. Two of the 4 patients experienced grade 1 acute veterinary radiation therapy oncology group (VRTOG) toxicity, and the 3 patients that completed their protocol experienced grade 1 late VRTOG toxicity. No radiation effects were documented to the cornea or lens in any patient. Superficial radiation therapy was effective in our limited study population, and patients experienced minimal side effects for treatment of cutaneous MCTs.

Differences in Quality of Life and Toxicity for Male and Female Patients following Chemo(radiotherapy) for Bladder Cancer

AimsBC2001, a randomised trial of treatment for muscle-invasive bladder cancer, demonstrated no difference in health-related quality of life (HRQoL) or late toxicity between patients receiving radical radiotherapy with and without chemotherapy. This secondary analysis explored sex-based differences in HRQoL and toxicity. Materials and methodsParticipants completed the Functional Assessment of Cancer Therapy Bladder (FACT-BL) HRQoL questionnaires at baseline, end of treatment, 6 months and annually until 5 years. Clinicians assessed toxicity with the Radiation Therapy Oncology Group (RTOG) and Late Effects in Normal Tissues Subjective, Objective and Management (LENT/SOM) scoring systems at the same timepoints. The impact of sex on patient-reported HRQoL was evaluated using multivariate analyses of change in FACT-BL subscores from baseline to the timepoints of interest. For clinician-reported toxicity, differences were compared by calculating the proportion of patients with grade 3–4 toxicities occurring over the follow-up period. ResultsFor both males and females, all FACT-BL subscores had a reduction in HRQoL at the end of treatment. For males, the mean bladder cancer subscale (BLCS) score remained stable through to year 5. For females, there was a decline in BLCS from baseline at years 2 and 3 with a return to baseline at year 5. At year 3, females had a statistically significant and clinically meaningful worsening of mean BLCS score (–5.18; 95% confidence interval –8.37 to –1.99), which was not seen in males (0.24; –0.76 to 1.23). RTOG toxicity was more frequent in females than males (27% versus 16%, P = 0.027). ConclusionResults suggest that female patients treated with radiotherapy ± chemotherapy for localised bladder cancer report worse treatment-related toxicity in post-treatment years 2 and 3 than males.

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.

Primary radiation therapy for advanced-stage laryngeal cancer: A laryngo-esophageal dysfunction disease-free survival.

To evaluate the outcomes of advanced-stage laryngeal squamous cell carcinoma (SCC) patients treated with functional-preservation strategy with a specific focus on laryngo-esophageal dysfunction disease-free survival (LEDDFS). A retrospective review was conducted of stage III-IVB laryngeal SCC patients who were treated with curative-intent radiotherapy (RT) (2007-2018). Patients were preferentially managed with upfront chemoradiation (CCRT); except for those with cN2-3, cT4, or large volume cT3 (induction chemotherapy followed by RT or CCRT is an option), and those who were unfit or declined chemotherapy (received altered RT). The primary endpoint was 3-year LEDDFS, and secondary endpoints were 3-year local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), disease-free survival (DFS), and acute and late toxicities. Cox proportional hazard tests were used for multivariable analysis (MVA). A total of 213 cases were included. With a median follow-up of 37 months, the 3-year LEDDFS was 50%, while the 3-year OS, DFS, LF, RF, and DM were 81%, 74%, 9%, 5%, and 7%, respectively. On MVA, cT4-category was the only predictor of inferior LEDDFS (HR: 0.47, [95% CI: 0.29-0.74], p < .01). The most common grade ≥ 3 acute and late radiation therapy oncology group (RTOG) toxicity were esophageal toxicity: 16.7% and 29.6%, respectively. Primary RT resulted in favorable oncologic and functional outcomes in only half of the advanced-stage laryngeal cancer patients. Future clinical trials are required to investigate further treatment options aiming to improve the oncologic and maintain functional outcomes with utilization of LEDDFS as the primary endpoint. 4.

Outcomes Associated with the Use of Tissue Equivalent Bolus Tailored by Skin Involvement Status in Postmastectomy Radiotherapy: A Single-Blinded Randomized Clinical Trial

<h3>Purpose/Objective(s)</h3> To assess the impact of tissue equivalent bolus in postmastectomy radiotherapy (PMRT), the present study compared the use of different bolus regimens tailored by skin involvement status. <h3>Materials/Methods</h3> Patients with breast cancer who required PMRT were recruited (NCT01925651) and divided in two subgroups: standard-risk (SR, without skin involvement) and high-risk (HR, with skin involvement). The SR was randomized between no bolus or 5mm-bolus on alternate days and the HR between 5mm-bolus on alternate days or 5mm-bolus daily. Skin changes were graded weekly with the Radiation Therapy Oncology Group (RTOG) toxicity scale (single-blinded). Subsequently, patients were followed to assess local control (LC) in the chest wall (CW). <h3>Results</h3> Fifty-eight patients were enrolled (34 SR and 24 HR). The median age was 48 years and 35.3% had BMI > 30 kg/m². All the baseline characteristics were similar between each arm within the same risk subgroup. The radiotherapy technique used was tridimensional (3D) in 30 cases (58.8%) and conventional (2D) in 21 cases (41.2%). Overall, the maximal radiodermatitis rates were 29.4% (G2) and 15.7% (G3). In the SR arms, there was no difference in the incidence of G2 radiodermatitis between no bolus and alternate days bolus (p=0.70), and no G3 event occurred. In the HR arms, the incidences of G2 (100% vs. 44.5%, p=0.01) and G3 radiodermatitis (70% vs. 11.1%, p=0.02) were higher with daily bolus. G2 events occurred earlier with daily bolus, but four of the six G3 events occurred 1-3 weeks after the last RT fraction. After a median follow-up of 6.2 years, the 5-year LC was 95.8% (95%CI: 88.2%-100%) in the SR and 91.7% (95%CI: 77.3%-100%) in the HR subgroups. Per randomization arm, there was no LC difference between the SR arms (p=0.90) or between the HR arms (p=0.70). All CW failures occurred in the tangent field's margins and when using 2D technique. <h3>Conclusion</h3> Within the same risk subgroup, no difference in LC was detected with a more intense bolus regimen. Due to increased G3 radiodermatitis and location of the CW failures (field borders), further studies testing the benefit of increasing superficial dose within the field (by adding bolus or increasing its intensity) are warranted.

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.

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study.

Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. Cancer Research UK, National Institute for Health Research.

PD54-07 COMPARATIVE EFFECTIVENESS ANALYSES OF SALVAGE PROSTATECTOMY AND SALVAGE RADIOTHERAPY OUTCOMES FOLLOWING FOCAL OR WHOLE-GLAND ABLATIVE THERAPY (HIGH INTENSITY FOCUSED ULTRASOUND (HIFU), CRYOTHERAPY OR ELECTROPORATION) FOR LOCALISED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD54-07 COMPARATIVE EFFECTIVENESS ANALYSES OF SALVAGE PROSTATECTOMY AND SALVAGE RADIOTHERAPY OUTCOMES FOLLOWING FOCAL OR WHOLE-GLAND ABLATIVE THERAPY (HIGH INTENSITY FOCUSED ULTRASOUND (HIFU), CRYOTHERAPY OR ELECTROPORATION) FOR LOCALISED PROSTATE CANCER Alexander Ng, Arjun Nathan, Anita Mitra, Prasanna Sooriakumaran, Reena Davda, Sonam Patel, Monty Fricker, John Kelly, Greg Shaw, Prabhakar Rajan, Ashwin Sridhar, Senthil Nathan, and Heather Payne Alexander NgAlexander Ng More articles by this author , Arjun NathanArjun Nathan More articles by this author , Anita MitraAnita Mitra More articles by this author , Prasanna SooriakumaranPrasanna Sooriakumaran More articles by this author , Reena DavdaReena Davda More articles by this author , Sonam PatelSonam Patel More articles by this author , Monty FrickerMonty Fricker More articles by this author , John KellyJohn Kelly More articles by this author , Greg ShawGreg Shaw More articles by this author , Prabhakar RajanPrabhakar Rajan More articles by this author , Ashwin SridharAshwin Sridhar More articles by this author , Senthil NathanSenthil Nathan More articles by this author , and Heather PayneHeather Payne More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002631.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ablative therapy, such as focal therapy, cryotherapy or electroporation, aims to treat clinically significant prostate cancer with reduced treatment-related toxicity. Up to a third of patients may require further local salvage treatment after ablative therapy failure. Limited descriptive, but no comparative, evidence exists between different salvage treatments. We compare oncological and functional outcomes after salvage robot-assisted radical prostatectomy (SRARP) and salvage radiotherapy (SRT). METHODS: Data were collected prospectively and retrospectively on 100 consecutive SRARP cases and 100 consecutive SRT cases, after ablative therapy failure, in a high-volume tertiary centre. RESULTS: High-risk patients were over-represented in the SRARP group (66.0%) compared to the SRT group (48.0%) (p=0.013). Median (IQR) follow-up after SRARP was 16.5 (10.0-30.0) months and 37.0 (18.5-64.0) months after SRT. SRT appeared to confer greater biochemical recurrence (BCR)-free survival at one, two and three years compared to SRARP in high-risk patients (year 3: 86.3% vs 66.0%), but BCR-free survival was similar for intermediate-risk patients (year 3: 90.0% vs 75.6%). There was no statistical difference in pad-free continence at 12- and 24-months between SRARP (77.2% and 84.7%) and SRT (75.0% and 74.0%) (p=0.724, 0.114). Erectile function was more likely to be preserved in men who underwent SRT. After SRT, cumulative bowel and urinary Radiation Therapy Oncology Group toxicity grade I were 25.0% and 45.0%, grade II were 11.0% and 11.0%, and grade III or IV complications were 4.0% and 5.0%, respectively. CONCLUSIONS: We report the first comparative analyses of salvage prostatectomy and radiotherapy following ablative therapy. Men with high-risk disease appear to have superior oncological outcomes after SRT; however, treatment allocation does not appear to influence oncological outcomes for men with intermediate-risk disease. Treatment allocation was associated with a different spectrum of toxicity profile. Our data may inform shared decision-making when considering salvage treatment following focal or whole-gland ablative therapy. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e918 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Ng More articles by this author Arjun Nathan More articles by this author Anita Mitra More articles by this author Prasanna Sooriakumaran More articles by this author Reena Davda More articles by this author Sonam Patel More articles by this author Monty Fricker More articles by this author John Kelly More articles by this author Greg Shaw More articles by this author Prabhakar Rajan More articles by this author Ashwin Sridhar More articles by this author Senthil Nathan More articles by this author Heather Payne More articles by this author Expand All Advertisement PDF DownloadLoading ...

Does stereotactic body radiation improve outcomes compared to conventional radiation for liver cancer patients?

IntroductionOver the past decade, there has been a paradigm shift to higher doses per fraction of liver stereotactic body radiotherapy (SBRT). However, this shift may not be due to evidence alone, but rather result of convenience and remuneration. This prospective cohort study aims to compare outcomes of patients who received moderately hypofractionated and hypofractionated radiotherapy treatments for liver tumours. MethodsPatients treated for liver cancer with radiotherapy between 2004 and 2020 were prospectively entered in this study. Patients were stratified into two groups: hypofractionation group of patients receiving an average of 5 fractions, and moderate hypofractionation group of patients receiving an average of 17 fractions. Other components of precision radiotherapy such as image guidance were the same between groups. The primary outcome was 2-year overall survival. The secondary outcomes were (1) change in toxicity as assessed by the Radiation Therapy Oncology Group (RTOG) toxicity criteria from baseline to 3 months, and from baseline to 6 months; and (2) change in Child Pugh score from baseline to 3 months. Type I error was prespecified at 0.05. Results397 patients were included. A larger proportion of patients on hypofractionated regimens were alive at the 2-year time point, relative to those who received moderately hypofractionated regimens (42% vs 27% p = 0.010); no difference was noted at the 1-year time point. Mean toxicity change in RTOG symptoms from baseline to 3 and 6 months, and in Child Pugh score from baseline to 3 months, were not statistically different between the two groups. ConclusionWhen compared to conventional radiation fractionation, liver SBRT tends to be associated with a significant overall survival benefit, justifying a randomized trial to confirm. The concern that the trend to higher dose per fraction may result in increased toxicity, specifically in the treatment of high-risk liver patients, appears to be unfounded. The hypofractionated component of SBRT may be the critical dosimetric factor impacting on survival.

Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis\u2014a\xa0safety analysis and validation of the EANO-ESMO classification

BackgroundAlthough there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known about the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO (European Association of Neuro-oncology—European Society for Medical Oncology) classification in this unique cohort.MethodsTreatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to RTOG (Radiation Therapy Oncology Group) toxicity criteria and NCI CTCAE V5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0). Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan–Meier analysis and Breslow test.ResultsIn all, 40 patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events ≥grade 3 according to RTOG toxicity criteria; in 22 patients (55%) NCI CTCAE ≥grade 3 were detected. Median overall survival was 124 days. Median time to neurological progression was 52 days. Patients with positive cerebrospinal fluid (CSF) cytology (n = 26) showed worse prognosis compared to patients with negative CSF cytology (n = 14; mOS (median overall survival) 84 days versus 198 days, p = 0.006, respectively). The EANO-ESMO response assessment was significantly associated with survival: “stable” (n = 7) mOS 233 days, “response” (n = 10) mOS 206 days, “progression” (n = 17) mOS 45 days, “suspicion of progression” (n = 6) mOS 133 days; overall, p < 0.001.ConclusionsIn this retrospective analysis, combined treatment of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile and may indicate a trend towards improved efficacy. The EANO-ESMO classification for diagnosis and treatment response predicts survival.

Comparison of Sequential Boost and Simultaneous Integrated Boost Volumetric Modulated Arc Therapy in Treatment of Head and Neck Carcinoma: A Prospective Interventional Study

Introduction: Volumetric Modulated Arc Therapy (VMAT) is a radiotherapy in head and neck cancer can be delivered by two boost techniques: Sequential Boost (SEQ) and Simultaneous Integrated Boost (SIB). There is still limited data comparing these two techniques. Aim: To compare SEQ and SIB planning techniques of VMAT in patients of Head And Neck Squamous Cell Carcinoma (HNSCC) in terms of disease response and acute toxicities. Materials and Methods: A prospective interventional study was conducted at Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India from January 2019 to December 2020. Fifty two patients of HNSCC planned for radical chemoradiation were enrolled into two study arms SEQ-VMAT and SIB-VMAT. Chemotherapy given as weekly cisplatin 40 mg/m2 . Dosimetric comparison was done using Dose Volume Histogram (DVH) analysis. Response evaluation was done as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 8-10 weeks follow-up. Acute toxicity evaluation was done as per Radiation Therapy Oncology Group (RTOG) toxicity grading. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 20.0 software. Results: A total of 52 subjects were included in the study, out of which 26 subjects were included in SEB group while 26 subjects in SIB group. No significant difference was observed in demographic data in terms of age 56.2 vs 53.5 years, sex (24 males and 2 females in both the arms), disease site (oropharynx is the most common site 38.5% in both arms)and stage (IVA 69.2% in SEQ arm vs 46.2% in SIB arm and III 30.8% in SEQ arm vs 42.3% in SIB arm). Dosimetric data was comparable between the two arms. SIB-VMAT shows significantly higher incidence of acute dermatitis (grade1 dermatitis at two weeks 69.2% vs 38.5%, p=0.0279 and grade 2 dermatitis at six weeks 84.6% vs 38.5%, p=0.0007) and acute mucositis (grade 1 mucositis at two weeks 84.6% vs 38.5%, p=0.0007) as compared to SEQ-VMAT. SEQVMAT shows significantly higher incidence of dysphagia (grade 1 at four weeks 84.5% vs 50%, p=0.0087). No significant differences were observed in terms of xerostomia and laryngeal toxicity.No significant difference in overall response was observed between SIB vs SEQ (complete response 65.4% vs 53.85% p=0.40). Conclusion: SEQ appears better in terms of acute toxicities but SIB was more convenient as no re-planning was required. For head and neck radiotherapy SIB and Sequential VMAT are comparable in terms of overall response.

THE EFFECT OF INTENSITY-MODULATED RADIOTHERAPY AND RECTUM VOLUME ON FORMATION OF ACUTE GASTROINTESTINAL TOXICITY IN PROSTATE CANCER

Objective: High-dose radiotherapy (RT) in prostate cancer has a high local control rate. Generally, the normal tissue toxicity of high doses is overlooked. We aimed to evaluate the rectal volume, diameter, and related dosimetric evaluation that may cause acute gastrointestinal (GIS) side effects in prostate cancer that we treated with intensity-modulated radiotherapy (IMRT). Method: Seventy-nine patients we treated with definitive or postoperative IMRT were evaluated for acute GIS toxicity according to Radiation Therapy Oncology Group (RTOG) toxicity criteria. The presence of acute GIS side effects and dosimetric parameters including grade and rectal volume and diameter were evaluated. Results: Seventy-nine patients treated with IMRT were evaluated. Acute GIS toxicity was observed in 21 (26.6%) patients after RT, Grade II side effects were observed in 7 (8.8%), and grade I acute side effects were observed in 14 (17.6%). Grade III and IV toxicity was not observed in any of the cases. No significant correlation was found between the grade of acute GIS side effects and the rectum values of V75, V65, V40, and V30 in dose-volume histograms (DVH), respectively, and rectal volume (cm3) and largest diameter (cm) measurements (p>0,05). The D median for definitive RT of PTV was 78 Gy, and the D median was 66 Gy for postoperative RT. No significant correlation was found between the occurrence of acute GIS side effects and grade of definitive or postoperative radiotherapy (p values, respectively, p=0.693, p=0.307). No significant correlation was found between the widest rectal diameter of less than 5 cm in planning and acute GIS side effects and acute GIS side effects Grade I (p=0.414, p=0.546). Conclusions: Prostate cancer treatment with IMRT had low rates of acute GIS toxicity. According to our study, the occurrence of acute GIS side effects was independent of rectal volume, diameter, and dosimetric parameters.

The Role of Patient- and Treatment-Related Factors and Early Functional Imaging in Late Radiation-Induced Xerostomia in Oropharyngeal Cancer Patients.

Simple SummaryIn the present prospective study, we assessed the role of various Magnetic Resonance Imaging biomarkers combined with self-assessed xerostomia questionnaires and patient- and treatment-related factors, in predicting xerostomia at 12 months after chemoradiotherapy for oropharyngeal squamous cell carcinoma. We hypothesized that the integration of pre-treatment imaging biomarkers, which addresses the tissue heterogeneity and individual variations among patients, could improve the accuracy of conventional prediction models that are based only on dose information, ultimately providing a better understanding of the pathophysiological mechanisms underlying radiation induced salivary dysfunction. The implementation of multifactorial models, driven by machine learning algorithms, may improve prediction accuracy of radiation-induced toxicity and tailor individual treatment options for patients.The advent of quantitative imaging in personalized radiotherapy (RT) has offered the opportunity for a better understanding of individual variations in intrinsic radiosensitivity. We aimed to assess the role of magnetic resonance imaging (MRI) biomarkers, patient-related factors, and treatment-related factors in predicting xerostomia 12 months after RT (XER12) in patients affected by oropharyngeal squamous cell carcinoma (OSCC). Patients with locally advanced OSCC underwent diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline; DWI was repeated at the 10th fraction of RT. The Radiation Therapy Oncology Group (RTOG) toxicity scale was used to evaluate salivary gland toxicity. Xerostomia-related questionnaires (XQs) were administered weekly during and after RT. RTOG toxicity ≥ grade 2 at XER12 was considered as endpoint to build prediction models. A Decision Tree classification learner was applied to build the prediction models following a five-fold cross-validation. Of the 89 patients enrolled, 63 were eligible for analysis. Thirty-six (57.1%) and 21 (33.3%) patients developed grade 1 and grade 2 XER12, respectively. Including only baseline variables, the model based on DCE-MRI and V65 (%) (volume of both glands receiving doses ≥ 65 Gy) had a fair accuracy (77%, 95% CI: 66.5–85.4%). The model based on V65 (%) and XQ-Intmid (integral of acute XQ scores from the start to the middle of RT) reached the best accuracy (81%, 95% CI: 71–88.7%). In conclusion, non-invasive biomarkers from DCE-MRI, in combination with dosimetric variables and self-assessed acute XQ scores during treatment may help predict grade 2 XER12 with a fair to good accuracy.

Quantitative assessments of late radiation-induced skin and soft tissue toxicity and correlation with RTOG scales and biological equivalent dose in breast cancer

PurposeRadiation-induced toxicity (RIT) is usually assessed by inspection and palpation. Due to their subjective and unquantitative nature, objective methods are required. This study aimed to determine whether a quantitative tool is able to assess RIT and establish an underlying BED-response relationship in breast cancer.MethodsPatients following seven different breast radiation protocols were recruited to this study for RIT assessment with qualitative and quantitative examination. The biologically equivalent dose (BED) was used to directly compare different radiation regimens. RIT was subjectively evaluated by physicians using the Radiation Therapy Oncology Group (RTOG) late toxicity scores. Simultaneously an objective multiprobe device was also used to quantitatively assess late RIT in terms of erythema, hyperpigmentation, elasticity and skin hydration.ResultsIn 194 patients, in terms of the objective measurements, treated breasts showed higher erythema and hyperpigmentation and lower elasticity and hydration than untreated breasts (p < 0.001, p < 0.001, p < 0.001, p = 0.019, respectively). As the BED increased, Δerythema and Δpigmentation gradually increased as well (p = 0.006 and p = 0.002, respectively). Regarding the clinical assessment, the increase in BED resulted in a higher RTOG toxicity grade (p < 0.001). Quantitative assessments were consistent with RTOG scores. As the RTOG toxicity grade increased, the erythema and pigmentation values increased, and the elasticity index decreased (p < 0.001, p = 0.016, p = 0.005, respectively).ConclusionsThe multiprobe device can be a sensitive and simple tool for research purpose and quantitatively assessing RIT in patients undergoing radiotherapy for breast cancer. Physician-assessed toxicity scores and objective measurements revealed that the BED was positively associated with the severity of RIT.

Comparative Effectiveness Analyses of Salvage Prostatectomy and Salvage Radiotherapy Outcomes Following Focal or Whole-Gland Ablative Therapy (High-Intensity Focused Ultrasound, Cryotherapy or Electroporation) for Localised Prostate Cancer

AimsAblative therapy, such as focal therapy, cryotherapy or electroporation, aims to treat clinically significant prostate cancer with reduced treatment-related toxicity. Up to a third of patients may require further local salvage treatment after ablative therapy failure. Limited descriptive, but no comparative, evidence exists between different salvage treatment outcomes. The aim of this study was to compare oncological and functional outcomes after salvage robot-assisted radical prostatectomy (SRARP) and salvage radiotherapy (SRT). Materials and methodsData were collected prospectively and retrospectively on 100 consecutive SRARP cases and 100 consecutive SRT cases after ablative therapy failure in a high-volume tertiary centre. ResultsHigh-risk patients were over-represented in the SRARP group (66.0%) compared with the SRT group (48.0%) (P = 0.013). The median (interquartile range) follow-up after SRARP was 16.5 (10.0–30.0) months and 37.0 (18.5–64.0) months after SRT. SRT appeared to confer greater biochemical recurrence-free survival at 1, 2 and 3 years compared with SRARP in high-risk patients (year 3: 86.3% versus 66.0%), but biochemical recurrence-free survival was similar for intermediate-risk patients (year 3: 90.0% versus 75.6%). There was no statistical difference in pad-free continence at 12 and 24 months between SRARP (77.2 and 84.7%) and SRT (75.0 and 74.0%) (P = 0.724, 0.114). Erectile function was more likely to be preserved in men who underwent SRT. After SRT, cumulative bowel and urinary Radiation Therapy Oncology Group toxicity grade I were 25.0 and 45.0%, grade II were 11.0 and 11.0% and grade III or IV complications were 4.0 and 5.0%, respectively. ConclusionWe report the first comparative analyses of salvage prostatectomy and radiotherapy following ablative therapy. Men with high-risk disease appear to have superior oncological outcomes after SRT; however, treatment allocation does not appear to influence oncological outcomes for men with intermediate-risk disease. Treatment allocation was associated with a different spectrum of toxicity profile. Our data may inform shared decision-making when considering salvage treatment following focal or whole-gland ablative therapy.

A Study Comparing Acute Toxicities of Cetuximab and Cisplatin in Patients Undergoing Definitive Chemoradiation With Intensity-Modulated Radiotherapy for Locally Advanced Carcinoma Head and Neck.

PurposeTo study the acute toxicities of weekly cetuximab used concurrently with intensity-modulated radiotherapy (IMRT) versus weekly cisplatin with concurrent IMRT in locoregionally advanced head and neck squamous cell carcinoma (HNSCC).Materials and methodsFifty eligible patients were randomly assigned to study group (cetuximab group) and control group (cisplatin group) to receive cetuximab 400 mg/m2 intravenously one week prior to the start of RT followed by 250 mg/m2/week, or weekly cisplatin intravenously 40 mg/m2, during RT. RT dose received was 70Gy in 35 fractions with 2Gy/fraction in both the arms with IMRT technique. Patients are reviewed every week and Patients were evaluated for acute toxicities according to radiation therapy oncology group (RTOG) toxicity scoring criteria and toxicities grade was reported.ResultsThe incidence of acute toxicities like oral mucositis, dysphagia, nausea, vomiting, and leukopenia were much less in cetuximab arm and statistically significant difference was observed as compared to cisplatin arm. and no major systemic toxicities were encountered in the cetuximab arm.ConclusionWeekly cetuximab with concurrent radiotherapy in locally advanced HNSCC is a promising regimen with well tolerable toxicity profile. Larger prospective randomized studies with a longer duration of follow-up with direct comparison of both the regimens are needed for strong evaluation of efficacy and toxicity profile.

Multiplatform Radiosurgery for Intracranial Meningiomas and Dose to the Dural Tail.

IntroductionMeningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail.MethodsFrom February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Development Co., Shenzhen, China]), TomoTherapy® (Tomo [Accuray Inc., Sunnyvale, CA]), and CyberKnife® (CK [Accuray Inc.]). All plans were retrospectively reviewed to establish the maximum distance (MaxDis) from the prescription dose to the end of the dural tail and the minimum dose at the dural tail (MinDoseT) at this point. We also established the midpoint distance (MPDis) from the prescription dose to MaxDis and the dose at this point (MPDose). Plans were further distinguished when the physician intended to cover the dural tail versus when not. Patients and tumor response were assessed by imaging and clinical and phone call evaluations.ResultsOf the 143 patients, 81 were treated using Gamma, 34 using Tomo, and 28 using CK. Eighty patients were eligible for follow-up, of whom 58 (72.5%) had an unmistakable dural tail sign. Median follow-up was 1,118 days (range 189-3,496), mean age was 54.5 (range 19-90), and 61 were women, and 19 were men. Overall tumor volume was 6.5 cc (range 0.2-59); mean tumor volumes by different platforms were 2.4, 9.45, and 8 cc; dose prescribed and mean tumor coverage were 14 Gy and 92%, 14.5 Gy and 95%, and 14 Gy and 95.75% with Gamma, Tomo, and CK, respectively. The dural tail was drawn and planned with an attempt to treat in 18 patients (31%); the mean MaxDis, MinDoseT, MPDis, and MPDose were 9.0 mm, 2 Gy, 4.5 mm, and 10.6 Gy, respectively. At last follow-up, tumor control was achieved in 96% of patients for the whole series, and there were no statistical variations regarding tumor volume, dose, conformality, or control when stereotactic radiosurgery was used to cover the dural tail versus when it was not (p=0.105). One patient experienced a Grade 4 Radiation Therapy Oncology Group toxicity as an adverse radiation effect that required surgery, and 11 (7.6%) experienced a Grade 1 toxicity.ConclusionsThis is our preliminary report regarding the efficacy of radiosurgery for meningiomas using diverse platforms at three years of follow-up; the results regarding tumor control are in accordance with the published literature as of this writing. A conscious pursuit of the dural tail with the prescription dose has not proven to provide better tumor control than not doing so - even small areas of the tumor uncovered by the prescription dose did not alter tumor control at current follow-up. The doses delivered to these uncovered areas are quite significant; further follow-up is necessary to validate these findings.

Helical tomotherapy for prostate cancer radiation therapy: An audit of early toxicity and quality of life

Radiation plays a major role in the management of localized prostate cancer (CaP). There are limited studies reporting the quality of life (QOL) and toxicity with CaP tomotherapy. This is a single-institutional prospective observational study evaluating the acute toxicity and QOL of patients with CaP receiving tomotherapy from May 2018 to October 2019. Toxicity assessed using radiation therapy oncology group toxicity grading. QOL assessed using International Prostate Symptom Score (IPSS) and QOL score. A total number of 74 patients received radiation therapy (RT), of which 25 had postoperative RT and 49 had radical RT. The median age was 71 years. During RT, 8 (10.8%) had Grade 2 gastrointestinal (GI) and 4 (5.4%) had Grade 2 genito urinary (GU) toxicities. At 3 months, 1 (1.4%) had Grade 2 GI, 1 (1.4%) had Grade 2 GU, and 1 (1.4%) had Grade 3 GU toxicities. At 6 months, 1 patient had Grade 2 GU and no Grade 2 GI toxicity noted. In postoperative RT Group, 2 (8%) Grade 2 GI and 1 (1.4%) Grade 2 genitourinary toxicity reported during radiation. At 3 months, 1 (1.4%) Grade 2 GI, 1 (1.4%) G2 GU, and 1 (1.4%) G3 GU toxicities noted. At 6 months, no ≥ Grade 2 noted. In radical RT group, during radiation 6 (12.2%) Grade 2 GI and 3 (6.1%) Grade 2 GU recorded. At 3 and 6 months, no ≥ Grade 2 GI/GU toxicity was recorded. No Grade 3/Grade 4 observed in radical RT group. One patient in radical RT and one in postoperative RT had severe IPSS symptom score. Results are comparable to reported studies. Our initial clinical experience with helical tomotherapy in CaP confirms lower rate of toxicities and no significant worsening of QOL with RT.