Radiation Therapy Oncology Group Scale Research Articles

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial

Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p=0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p=0.004). The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. This study was funded by Science and Engineering Research Board (SERB), India.

Safety of Ultrahypofractionated Pelvic Nodal Irradiation in the Definitive Management of Prostate Cancer: Systematic Review and Meta-analysis

Aim: This systematic review and meta-analysis aimed to evaluate the evidence for ultra-hypofractionated pelvic nodal irradiation in prostate cancer patients, with a focus on reported acute and late toxicities. Methods: A comprehensive search was conducted in five electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, Clinicaltrials.gov) from inception until 23 March 2023. Eligible publications included patients with intermediate- and high-risk and node positive prostate cancer who underwent elective or therapeutic ultra-hypofractionated pelvic nodal irradiation. Primary outcomes included the presence of grade ≥2 rates of acute and late gastrointestinal and genitourinary toxicity based on the Common Terminology Criteria for Adverse Events (CTCAE) scale or Radiation Therapy Oncology Group (RTOG) scales. Quality assessment was performed using NIH tools for non-controlled before and after clinical trials, as well as single-arm observational studies. Since all outcomes were categorical variables, proportion was calculated to estimate the effect size and compare the outcomes after the intervention. Results: We identified 16 publications that reported the use of ultra-hypofractionated radiotherapy to treat the pelvis in prostate cancer. Seven publications met our criteria and were included in the meta-analysis, including 417 patients. The median total dose to the pelvic lymph nodes was 25 Gy (range: 25 - 28.5 Gy), with a median of 5 fractions. The prostate received a median dose of 40 Gy (range: 35 to 47.5 Gy). All studies utilized androgen deprivation therapy for a median duration of 18 months. The median follow-up period was 3 years (range: 0.5-5.6 years). The rates of acute grade ≥2 gastrointestinal and genitourinary toxicity were 8% (CI 95%: 1% to 15%) and 29% (CI 95%: 18% to 41%), respectively. For late grade ≥2 gastrointestinal and genitourinary toxicity, the rates were 13% (CI 95%: 5% to 21%) and 29% (CI 95%: 17% to 42%), respectively. Conclusion: Ultra-hypofractionated pelvic nodal irradiation appears to be a safe approach in terms of acute and late genitourinary and gastrointestinal toxicity.

Toxicity and Efficacy of Hypofractionated Regional Nodal Irradiation

Hypofractionated whole-breast irradiation (HF-WBI) has been widely adopted. However, there are still limited data on whether hypofractionated regional nodal irradiation (HF-RNI) is safe and effective. We report toxicity and cancer outcomes with our HF-RNI approach. This retrospective study included 154 patients with node-positive or high-risk node-negative breast cancer treated with HF-RNI with curative intent at a single academic institution from 2008-2020. Median dose to the breast or chest wall/reconstructed breast was 40 Gy in 16 fractions (interquartile range [IQR], 40-45 Gy in 16-18 fractions). Median dose to the regional nodes was 40 Gy in 16 fractions (IQR, 40-40 Gy in 16-16 fractions). The primary end-point was the rate of chronic toxicity. Secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), disease-free survival (DFS), and overall survival (OS). Toxicities were scored using the Common Terminology Criteria for Adverse Events v5.0 and Radiation Therapy Oncology Group scale where appropriate. This study was approved by the Institutional Review Board. Median follow-up was 46 months (IQR 33-63 mo). Median age at diagnosis was 58 years. Sentinel lymph node biopsy (SLNB) was performed in 49% of patients, 16% underwent both SLNB and axillary lymph node dissection (ALND), 32% underwent ALND alone, and 3% had no axillary surgery; 79% had partial mastectomy and 21% had total mastectomy with or without reconstruction. The nodal target included the supraclavicular and axillary Level 1-3 nodes in 66% of patients and supraclavicular and Level 3 nodes in 34%. The crude incidence of grade 1 chronic brachial plexopathy was 2%, grade 1 chronic limited range of motion (LROM) of the upper extremity was 3%, and chronic upper extremity lymphedema was 8% (11 patients with grade 1 toxicity and 1 patient with grade 2 toxicity). The only grade 3+ chronic toxicity was hyperpigmentation (1%). The median time to the development of the highest-grade toxicity was 10 months for brachial plexopathy, 10 months for LROM, and 11 months for lymphedema, respectively. Five-year actuarial rates of LRFS, RRFS, DFS, and OS were 98%, 99%, 90%, and 88%, respectively. HF-RNI resulted in low rates of chronic toxicities and excellent disease control in this study. Results of randomized trials of HF-RNI are needed for definitive evidence, but these retrospective data support wider adoption of HF-RNI.

A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. ClinicalTrials.gov, identifier NCT40155531.

Topical corticosteroids for the prevention of severe radiation dermatitis: a systematic review and meta-analysis.

Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for the treatment of RD, its role in preventing severe reactions remains unclear. This systematic review and meta-analysis aim to evaluate the evidence on the use of TCs as prophylaxis of RD. A systematic search was conducted using OVID MedLine, Embase, and Cochrane databases (between 1946 and 2023) to identify studies examining TC use in the prevention of severe RD. Statistical analysis was completed using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals. Forest plots were then developed using a random effects model. Ten RCTs with a total of 1041 patients met the inclusion criteria. Six studies reported on mometasone furoate (MF) and four studies reported on betamethasone. Both TCs were associated with a significant improvement in the prevention of moist desquamation [OR = 0.34, 95% CI [0.25, 0.47], p < 0.00001], but betamethasone was found to be more effective than MF [OR = 0.29, 95% CI [0.18, 0.46], p < 0.00001 and OR = 0.39, 95% CI [0.25, 0.61], p < 0.0001, respectively]. A similar finding was seen in reducing the development of grade 2 or higher RD according to the Radiation Therapy Oncology Group scale. The current evidence supports the use of TCs in preventing severe reactions of RD. Both MF and betamethasone were found to be effective; however, betamethasone, a higher potency TC, is more effective despite MF being more commonly reported in literature.

Topical non-steroidal agents for the prevention of radiation dermatitis: a systematic review and meta-analysis.

Radiation dermatitis (RD) is a common side effect of radiation therapy, affecting a majority of breast and head and neck cancer patients with a negative impact on quality of life. Currently, no consensus exists regarding the prevention of RD. PubMed, Embase and Cochrane databases (1946 to December 2022) were searched using PRISMA guidelines to identify randomized controlled trials (RCTs) that investigated the use of topical non-steroidal agents in the prevention of RD in patients undergoing radiotherapy. A total of six RCTs were included, comprising 627 patients. Among the topical non-steroidal agents analyzed, only the use of Biafine® in breast cancer patients was significant in preventing grade 4 and 3 + RD as classified by the Radiation Therapy Oncology group (RTOG) scale (OR = 0.07, 95% CI 0.01-0.63, p = 0.02, and OR 0.11, 95% CI 0.03-0.41, p < 0.01, respectively). The remaining agents (trolamine alone and hyaluronic acid/hyaluronan) did not significantly prevent the occurrence of RD. The results of this systematic review and meta-analysis indicate that Biafine® can prevent grade 3 + RD in breast cancer patients. The use of trolamine and hyaluronic acid does not significantly affect the incidence of RD.

Volumetric Intensity-Modulated Arc Stereotactic Radiosurgery Boost in Oligometastatic Patients with Spine Metastases: a Dose-escalation Study

AimsTo report the final results of a dose-escalation study of volumetric intensity-modulated arc stereotactic radiosurgery (VMAT-SRS) boost after three-dimensional conformal radiation therapy in patients with spine metastases. Materials and methodsOligometastatic cancer patients bearing up to five synchronous metastases (visceral or bone, including vertebral ones) and candidates for surgery or radiosurgery were considered for inclusion. 25 Gy was delivered in 10 daily fractions (2 weeks) to the metastatic lesion, affected vertebrae and adjacent ones (one cranial and one caudal vertebra). Sequentially, the dose to spinal metastases was progressively increased (8 Gy, 10 Gy, 12 Gy) in the patient cohorts. Dose-limiting toxicities were defined as any treatment-related non-hematologic acute adverse effects rated as grade ≥3 or any acute haematological toxicity rated as ≥ 4 by the Radiation Therapy Oncology Group scale. ResultsFifty-two lesions accounting for 40 consecutive patients (male/female: 29/11; median age: 71 years; range 40–85) were treated from April 2011 to September 2020. Most patients had a primary prostate (65.0%) or breast cancer (22.5%). Thirty-two patients received 8 Gy VMAT-SRS boost (total BED α/β10: 45.6 Gy), 14 patients received 10 Gy (total BED α/β10: 51.2 Gy) and six patients received 12 Gy (total BED α/β10: 57.6 Gy). The median follow-up time was over 70 months (range 2–240 months). No acute toxicities > grade 2 and no late toxicities > grade 1 were recorded. The overall response rate based on computed tomography/positron emission tomography–computed tomography/magnetic resonance was 78.8%. The 24-month actuarial local control, distant metastases-free survival and overall survival rates were 88.5%, 27.1% and 90.3%, respectively. ConclusionA 12 Gy spine metastasis SRS boost following 25 Gy to the affected and adjacent vertebrae was feasible with an excellent local control rate and toxicity profile.

Efficacy of Epigallocatechin-3-Gallate in Preventing Dermatitis in Patients With Breast Cancer Receiving Postoperative Radiotherapy

Safe and effective prophylactic therapies for radiation-induced dermatitis (RID) remain an unmet need. To determine if epigallocatechin-3-gallate (EGCG) solution reduces the incidence of RID in patients undergoing radiotherapy after breast cancer surgery. This phase 2 double-blind, placebo-controlled randomized clinical trial enrolled 180 patients with breast cancer receiving postoperative radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China, between November 2014 and June 2019. Data analysis was performed from September 2019 to January 2020. Participants were randomly assigned (2:1) to receive either EGCG solution (660 μmol/L) or placebo (0.9% NaCl saline) sprayed to the whole radiation field from day 1 of the radiation until 2 weeks after radiation completion. The primary end point was incidence of grade 2 or worse RID, defined by the Radiation Therapy Oncology Group scale. The secondary end points included RID index (RIDI), symptom index, changes in the skin temperature measured by infrared thermal images, and safety. A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]). In this randomized clinical trial, prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer. It has the potential to become a new choice of skin care for patients receiving radiotherapy. ClinicalTrials.gov Identifier: NCT02580279.

Urinary toxicity in patients treated with radical EBRT for prostate cancer: Analysis of predictive factors in an historical series

The present study aims to identify predictive factors for urinary toxicity and self-reported symptoms after external beam radiotherapy (EBRT) for prostate cancer. Two-hundred and eighty patients treated with EBRT for prostate cancer were included in the present study. Toxicity was scored following the grading system based on Radiation Therapy Oncology Group (RTOG) scale. International Prostatic Symptom Score (IPSS) and Consultation on Incontinence Questionnaires-Short Form (ICIQ-SF) were used to analyse self-reported symptoms. Acute and late urinary toxicities were correlated to clinical and treatment parameters, radiation dosimetry data, IPSS and ICIQ-SF. Median patient age was 74 years (range, 64-83). Thirty-one percent experienced acute G1 urinary toxicity, 24% G2 and 3% G3. Fourteen percent experienced G1 late urinary toxicity and 3% G2. Bladder volume<200 cc was associated with acute urinary toxicity (P=0.014); use of MRI for treatment planning allowed a lower incidence of late toxicity (P=0.062) and use of IMRT allowed for reduced incidence in late toxicity (P=0.038). Maximum bladder dose correlated with late urinary toxicity (P=0.014). The analysis of self-reported symptoms showed a significant correlation between IPSS baseline values (P=0.009), presence of nocturia (P=0.002), bladder urgency (P=0.024) and incontinence (P=0.024) and development of acute urinary toxicity at univariate analysis. At multivariate logistic regression analysis, bladder filling, IPSS value, nocturia, and urinary incontinence retained significant correlation with acute toxicity (P=0.0003). Significant independent predictors for acute urinary toxicity grade≥2 were bladder filling, IPSS value, nocturia, and urinary incontinence at baseline assessment.

How to manage radiation-induced dermatitis?

Radiotherapy is one of the treatment methods available for cancer patients. More than half of all cancer patients tre­ated with radiotherapy will experience radiodermatitis during their treatment. There are two commonly used scales to evaluate clinical manifestations: Common Terminology Criteria for Adverse Events (CTCAE) and the Radiation Therapy Oncology Group (RTOG) scale. According to them, the severity of radiation dermatitis ranges from mild erythema to moist desquamation and ulceration. Prevention methods for radiation dermatitis include proper skin hygiene, the use of topical corticosteroids, other non-corticosteroid agents and systemic drugs. Treatment of radiation dermatitis is guided by the severity of skin damage. In grade 1 it can be limited to moisturising the irritated skin field but in more severe reactions (grade 2–4) the use of dressing is essential. There is still a need to investigate new products, techniques or novel approaches to minimize, prevent or treat radiation dermatitis in patients undergoing radiotherapy.

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.

Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers.

The ability to consistently and accurately assess oral mucositis (OM) is critical to descriptions of its incidence and severity and in evaluating the effectiveness of potential interventions. The lack of a single grading scale compounds outcome interpretation. Consequently, we assessed the concordance of three of the most commonly used OM grading criteria (World Health Organization (WHO), Radiation Therapy Oncology Group (RTOG), and the common terminology criteria for adverse events (CTCAE). Data was evaluated from two hundred patients with oropharyngeal or oral cavity cancers who underwent chemoradiation therapy and were enrolled in a double-blind, randomized, placebo-controlled trial in which trained assessors evaluated patients twice weekly. WHO, RTOG, and CTCAE scores were assigned centrally by independent evaluators blinded to the study group. Concordance among the three scales for all OM scores and severe OM scores (score ≥ 3) was defined as the percentage agreement and measured using Cohen's weighted Kappa. Of 3,578 OM assessments, 57% had identical scores for all three scales. When any score was considered, the concordance between WHO and RTOG scales was 71% (kappa 0.58; 95%CI: 0.56-0.60), 62% for the WHO and CTCAE scales (kappa 0.46; 95%CI: 0.44-0.48) and 78% for the CTCAE and RTOG scales (kappa 0.69; 95%CI: 0.68-0.71). When patients had severe OM (WHO score ≥ 3), 99.6% (521/523) of the CTCAE OM assessments had scores of 3 or 4 (kappa 0.98; 95%CI: 0.98-0.999) and 97.7% of the RTOG ones (511/523) had scores of 3 or 4 (kappa 0.69; 95%CI: 0.62-0.75). Among patients who had a WHO score of 4, 31.7% (63/199) and 96.0% (196/199) of patients had RTOG or CTCAE scores of 2 or 3, respectively. Discordance was seen with patients who exhibited mild to moderate OM or most severe OM (grade 4) as described by WHO criteria. Whereas scale selection seems less critical in studies in which general "severe mucositis" is the primary outcome, it is particularly important in accurately describing OM's clinical trajectory and the frequency and impact in its most severe forms.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05Gy) and SIB to the TB (48Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6months. At univariate analysis, age < 40years, breast volume > 1000cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

HDR brachytherapy boost using MR-only workflow for intermediate- and high-risk prostate cancer: 8-year results of a pilot study

PurposeTo report 8-year clinical outcome with high-dose-rate brachytherapy (HDRBT) boost using MRI-only workflow for intermediate (IR) and high-risk (HR) prostate cancer (PC) patients. Methods and MaterialsFifty-two patients were treated with 46–60 Gy of 3D conformal radiotherapy preceded and/or followed by a single dose of 8–10 Gy MRI-guided HDRBT. Interventions were performed in a 0.35 T MRI scanner. Trajectory planning, navigation, contouring, catheter reconstruction, and dose calculation were exclusively based on MRI images. Biochemical relapse-free- (BRFS), local relapse-free- (LRFS), distant metastasis-free- (DMFS), cancer-specific-(CCS) and overall survival (OS) were analyzed. Late morbidity was scored using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) combined with RTOG (Radiation Therapy Oncology Group) scale for urinary toxicity and rectal urgency (RU) determined by Yeoh. ResultsMedian follow-up time was 107 (range: 19–143) months. The 8-year actuarial rates of BRFS, LRFS, DMFS, CSS and OS were 85.7%, 97%, 97.6%, and 77.6%, respectively. There were no Gr.3 GI side effects. The 8-year actuarial rate of Gr.2 proctitis was 4%. The 8-year cumulative incidence of Gr.3 GU side effects was 8%, including two urinary stenoses (5%) and one cystitis (3%). EPIC urinary and bowel scores did not change significantly over time. ConclusionsMRI-only HDR-BT boost with moderate dose escalation provides excellent 8-year disease control with a favorable toxicity profile for IRPC and HRPC patients. Our results support the clinical importance of MRI across the BT workflow.

Topical treatments to reduce severity of radiation dermatitis in breast cancer patients-a systematic review

Breast cancer (BC) patients are likely to undergo radiotherapy (RT) treatment which may lead to the development of the skin toxicity, radiodermatitis (RD). The purpose of this systematic review is to evaluate the effectiveness of topical interventions in reducing the severity of RD in females BC patients. Appropriate clinical studies were independently identified through a bibliographic search in PubMed and clinicaltrials.gov. Nine randomised, controlled clinical trials (RCTs) which stated a clear inclusion and exclusion criteria, were included in this review. The studies included in this review were conducted in the last 10 years and researched the effectiveness of only topical therapies on female BC patients. The severity of RD starting at baseline 0 to endpoint was measured using the Radiation Therapy Oncology Group (RTOG) scale, and results show most patients experienced a RTOG score change of 0-1 or 0-2. A significant relationship between results obtained from 0-1 and 0-2 was shown (p &lt; 0.00001). Results suggest Radioskin 1&amp;2 cream is the most effective topical treatment for RD as 95% of patients experienced a RTOG score change of 0-1 compared to 5% experiencing 0-2. However, controlled treatments like general care and Aqua Cream seem to be the least effective, as 1.9% of patients administrating general care experienced a RTOG score change of 0-1 compared to 41.9% experiencing 0-2.

A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX

In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75%compliance, n=112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P=0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P=0.012). Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.

Quantitative 3-Dimensional Photographic Assessment of Breast Cosmesis After Whole Breast Irradiation for Early Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial

PurposeOur purpose was to use 3-dimensional (3D) surface photography to quantitatively measure breast cosmesis within the framework of a randomized clinical trial of conventionally fractionated (CF) and hypofractionated (HF) whole breast irradiation (WBI); to identify how 3D measurements are associated with patient- and physician-reported cosmesis; and to determine whether objective measures of breast symmetry varied by WBI treatment arm or transforming growth factor β 1 (TGFβ1) status. Methods and MaterialsFrom 2011 to 2014, 287 women age ≥40 with ductal carcinoma in situ or early-stage invasive breast cancer were enrolled in a multicenter trial and randomized to HF-WBI or CF-WBI with a boost. Three-dimensional surface photography was performed at 3 years posttreatment. Patient-reported cosmetic outcomes were recorded with the Breast Cancer Treatment Outcome Scale. Physician-reported cosmetic outcomes were assessed by the Radiation Therapy Oncology Group scale. Volume ratios and 6 quantitative measures of breast symmetry, termed F1-6C, were calculated using the breast contour and fiducial points assessed on 3D surface images. Associations between all metrics, patient- and physician-reported cosmesis, treatment arm, and TGFβ1 genotype were performed using the Kruskal-Wallis test and multivariable logistic regression models. ResultsAmong 77 (39 CF-WBI and 38 HF-WBI) evaluable patients, both patient- and physician-reported cosmetic outcomes were significantly associated with the F1C vertical symmetry measure (both P < .05). Higher dichotomized F1C and volumetric symmetry measures were associated with improved patient- and physician-reported cosmesis on multivariable logistic regression (both P ≤ .05). There were no statistically significant differences in vertical symmetry or volume measures between treatment arms. Increased F6C horizontal symmetry was observed in the CF-WBI arm (P = .05). Patients with the TGFβ1 C-509T variant allele had lower F2C vertical symmetry measures (P = .02). ConclusionsQuantitative 3D image-derived measures revealed comparable cosmetic outcomes with HF-WBI compared with CF-WBI. Our findings suggest that 3D surface imaging may be a more sensitive method for measuring subtle cosmetic changes than global patient- or physician-reported assessments.

The Impact of Radiodermatitis on Breast Cancer Patients' Quality of Life During Radiotherapy: A Prospective Cohort Study

ContextIn the oncology field, quality of life (QoL) is recognized as an essential component. However, few studies have evaluated radiotherapy (RT) and its adverse events, specifically radiodermatitis. ObjectivesThe objective of this study was to investigate the influence of radiodermatitis severity on QoL of women with breast cancer (BC) throughout RT. MethodsA prospective cohort study was conducted with 100 BC patients evaluated weekly during RT. The Dermatology Life Quality Index questionnaire and the Radiation Therapy Oncology Group scale were used. The generalized estimated equations were used to examine the association between the total score of QoL and their domains, time of RT, and the radiodermatitis score, controlled by confounding factors. Estimated marginal means and 95% CIs were compared pairwise by applying Sequential Sidak. ResultsThe total QoL score and their domains (work/school, leisure, daily activities, symptoms, and feelings) were significantly associated with the evaluation times of RT (P < 0.001), the radiodermatitis score (P ≤ 0.002), and the interaction between timing (T) of treatment and radiodermatitis score (P < 0.001). When assessing post hoc, it was identified that the worst QoL scores were in the presence of Grade 3 (mean = 6.00) in T3 and Grade 4 (6.50; 7.00) in T5 and T6, respectively, and this difference was statistically significant. ConclusionsRT negatively influenced the QoL of women with BC, with the greatest impact resulting from severe radiodermatitis. Actions aimed at minimizing the impairment on QoL need to be adopted to make this exhausting process less traumatic and easier to complete.

Is there agreement between evaluators that used two scoring systems to measure acute radiation dermatitis?

To analyze the agreement between the nurses evaluating radiodermatitis that used the Radiation Therapy Oncology Group (RTOG) and the World Health Organization (WHO) scales.A prospective and longitudinal study conducted in 2016 to 2017, in a university hospital. We analyzed 855 images of irradiated sites of 100 breast cancer women during radiotherapy. In order to evaluate the agreement between 3 observers that evaluated theses irradiated sites Krippendorff's alpha and weighted kappa were obtained and analyzed.The pairwise agreement among the evaluators was fair and moderate (RTOG scale: 0.408, 95% confidence interval, CI 0.370–0.431; WHO scale: 0.559, 95% CI 0.529–0.590). In addition, the general agreement rates were 10.2% and 29.2%, respectively. When assessing the overall absolute agreement between the evaluators according with different phototypes and types of surgery, there was a fair agreement according to the RTOG scale when evaluating patients with phototype V or VI and mastectomy (3.7% and 8.8%, respectively).The RTOG and WHO scales should be used with caution in clinical practice to identify the prevalence of radiodermatitis and the severity. Another point of caution is that skin phototype and the type of surgery may influence the analysis outcome. An illustrative scale was designed and proposed, by our group, aiming to improve accuracy and agreement between evaluators that will be tested in subsequent clinical studies.

Homeopathy and Complementary Integrative Medicine, Dietary and Lifestyle Advices to Reduce Adverse-Effects of Anti-Cancer Therapy: A Cohort Study with Breast Cancer Patients

Background. To face adverse-effects of anti-cancer treatment, the Homeopathic Clinic of Lucca, in collaboration with the Oncology Department, has set up an Integrative Oncology Outpatient Unit in the Public Hospital Campo di Marte, Aim. To present the results of complementary medicine (CM) treatment targeted towards reducing the adverse effects of anti-cancer therapy and cancer symptoms and improving the quality of life of breast cancer patients. Methods. This is a retrospective observational study conducted on 204 breast cancer patients (all females except 1 male) were consecutively visited from September 2013 to December 2017, mean age 54.8 (35-88) years. Almost all patients were referred by their medical oncologists. The intensity of symptoms was evaluated according to a grading system from G0 (absence of symptoms) to G1 (slight), G2 (moderate), and G3 (strong), as evaluated by the patient in conjunction with the doctor during the course of the visits. The severity of radiodermatitis was evaluated with the Radiation Therapy Oncology Group (RTOG) scale. Homeopathy was the main prescribed therapy, either exclusive (47.5%) or integrated with other complementary medicines (41.7%), mainly botanicals and acupuncture. The Banerji protocol was applied in 3.4% of patients. Results. The most frequently treated symptoms were the adverse-effects of anti-cancer therapies (84.3%): endocrine therapy (36.3%), chemotherapy (33.3%), radiotherapy (9.8%) and surgery (4.9%). The symptoms caused by cancer disease were 25.5%, and comorbidity 21.6%. Comparison of the clinical conditions before and after treatment allowed to observe a significant amelioration of the following symptoms: hot flashes (p < 0.01); nausea (p < 0.01); fatigue (p < 0.01); anxiety (p < 0.05); depression (p < 0.01); insomnia (p < 0.01); mucositis (p < 0.01); joint pain (p < 0.01) . Conclusions. A clinic of integrative oncology is an opportunity to reduce adverse-effects of anti-cancer therapy and to ameliorate cancer patients’ quality of life.