Radiation Therapy Oncology Group Research Articles

Doses delivered to small and large breasts and adjacent organs in left breast cancer patients utilizing 3D and IM radiotherapy

BackgroundRadiotherapy is still the most facilitated modality for treatment of malignant tumors, including breast cancer, with or without chemotherapy and after surgery or when surgery is impossible. AimThe present article concerns a number of parameters used in radiation therapy techniques, involving the minimum, maximum, mean dose, volume covered with 95% of dose, and global maximum dose delivered to planning target volume (PTV), and the organs at risk, including left lung, heart, thyroid gland, spinal cord, humerus, super clavicle lymph node, and the right breast using the constraints of Radiation Therapy Oncology Group (RTOG). Patients and MethodsTwenty patients with breast tumors, females only, were enrolled in the study. A LINAC with a 6 MV photon beam was used to deliver the prescribed dose. The whole breast irradiation was applied to each patient using two planning techniques: 3D conformal and intensity modulated radiotherapy, and the planning was constructed within 95%–107% of the prescribed dose to the planning target volume as recommended by the RTOG. ResultsThe results showed a significant difference (at the level of P < 0.05) between the two planning techniques based on the doses received by PTV and the OARs. The results were discussed. ConclusionWe concluded that inverse intensity modulation radiation therapy (IMRT) for breast cancer does not improve late toxicity or oncologic outcomes. So, inverse IMRT is not yet the norm, and health insurance usually doesn't pay for treatment unless it's absolutely necessary, like to stop a heart attack. .

Racial survival disparities in head and neck cancer clinical trials.

Survival disparities between Black and White head and neck cancer patients are well documented, with access to care and socioeconomic status as major contributors. We set out to assess the role of self-reported race in head and neck cancer by evaluating treatment outcomes of patients enrolled in clinical trials, where access to care and socioeconomic status confounders are minimized. Clinical trial data from the Radiation Therapy Oncology Group studies were obtained. Studies were included if they were therapeutic trials that employed survival as an endpoint. Studies that did not report survival as an endpoint were excluded; 7 Radiation Therapy Oncology Group Studies were included for study. For each Black patient enrolled in a clinical trial, a study arm-matched White patient was used as a control. A total of 468 Black participants were identified and matched with 468 White study arm-specific controls. White participants had better outcomes than Black participants in 60% of matched pairs (P < .001). Black participants were consistently more likely to have worse outcomes. When outcomes were measured by progression-free survival or disease-free survival, the failure rate was statistically significantly higher in Black participants (hazard ratio [HR] = 1.50, P < .001). Failure was largely due to locoregional failure, and Black participants were at higher risk (subdistribution HR =1.51, P = .002). The development of distant metastasis within the paired cohorts was not statistically significantly different. In this study of clinical trial participants using self-reported race, Black participants consistently had worse outcomes in comparison to study arm-specific White controls. Further study is needed to confirm these findings and to explore causes underlying this disparity.

Electronic Portal Imaging Device in Pre-Treatment Patient-Specific Quality Assurance of volumetric-modulated arc therapy delivery

Abstract Background: Radiotherapy treatment delivery is evaluated by a pre-treatment patient-specific quality assurance (PSQA) procedure to ensure the patient receives an accurate radiation dose. The current PSQA practice by using conventional phantoms requires more set-up time and cost of purchasing the tools. Therefore, this study aimed to investigate the efficiency of an electronic portal imaging device (EPID) of linear accelerator (LINAC) as a PSQA tool for volumetric-modulated arc therapy (VMAT) planning technique for nasopharyngeal carcinoma (NPC) treatment delivery. Methods: A NPC VMAT plan on a Rando phantom was performed by following the Radiation Therapy Oncology Group (RTOG) 0615 protocol. The gamma passing rate of the EPID and PSQA phantom (ArcCHECK) were compared among the gamma criteria of 3%/3 mm, 2%/2 mm and 1%/1 mm, respectively. Results: Both EPID and ArcCHECK phantom had distinguishable gamma passing rates in 3%/3 mm and 2%/2 mm with a difference of 0·87% and 0·30%, respectively. Meanwhile, the EPID system had a lower gamma passing rate than the ArcCHECK phantom in 1%/1 mm (21·23% difference). Furthermore, the sensitivity of the EPID system was evaluated and had the largest deviation in gamma passing rate from the reference position in gamma criteria of 2%/2 mm (41·14%) compared to the 3%/3 mm (25·45%) and 1%/1 mm (31·78%), discretely. The best fit line of the linear regression model for EPID was steeper than the ArcCHECK phantom in 3%/3 mm and 2%/2 mm, and vice versa in gamma criteria of 1%/1 mm. This indicates that the EPID had a higher sensitivity than the ArcCHECK phantom in 3%/3 mm and 2%/2 mm but less sensitivity in 1%/1 mm. Conclusions: The EPID system was efficient in performing the PSQA test of VMAT treatment in HUSM with the gamma criteria of 3%/3 mm and 2%/2 mm.

Clinical Outcome and Risk Factors of Chronic Radiation Proctitis Following Pelvic Radiation Therapy.

Pelvic radiation therapy (RT) is a common treatment for malignancies, including gynecological, genitourinary, and lower gastrointestinal tract cancers. However, chronic radiation proctitis (RP) is an unavoidable side effect, and its clinical presentation varies from asymptomatic to potentially life-threatening. This study evaluated the clinical characteristics and risk factors of chronic RP. Patients with chronic RP (212) following RT for various pelvic cancers between January 2015 and December 2021 were enrolled. Clinical characteristics of RP were analyzed retrospectively. Severity was graded according to the Radiation Therapy Oncology Group (RTOG) modified rectal toxicity score and Vienna rectoscopy score (VRS), and risk factors were statistically analyzed. The most common pelvic cancer observed was cervical cancer. The patients received three-dimensional conformal RT (3D-CRT), intensity-modulated RT, or a combination of 3D-CRT and intracavitary RT (ICR). Rectal bleeding occurred in 70 (33.0%) patients. Previous abdominopelvic surgery and total radiation dose significantly correlated with the RTOG score and VRS. Previous abdominopelvic surgery, ICR, and total radiation dose were associated with chronic hemorrhagic RP. All patients with chronic hemorrhagic RP were treated with argon plasma coagulation (APC). 91.4% of cases required 1-3 APC sessions to resolve the bleeding, with a mean of 1.7 sessions. Our results showed that previous abdominopelvic surgery and total radiation dose were significant risk factors related to chronic RP, while total radiation dose was related to chronic hemorrhagic RP. We also showed that APC was effective and safe for chronic hemorrhagic RP.

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.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy

Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

Dummy run quality assurance study in the Korean Radiation Oncology Group 19 − 09 multi-institutional prospective cohort study of breast cancer

BackgroundThe Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run.MethodsTwelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans.ResultsWe found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans.ConclusionWe found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

"Big Boom" (4 Gy x 1) Radiation Treatment (RT) Versus "Big Boom" (2 Gy x 2) for Non-Hodgkin Lymphoma (NHL)

Purpose/Objectives Indolent lymphomas are exquisitely sensitive to radiation. Recently, programs of only 4 Gy in 2 daily fractions (Boom-Boom) were shown to be highly effective in controlling irradiated site(s). During the COVID-19 pandemic, the International Lymphoma Radiation Oncology Group (ILROG) proposed guidelines that allowed substitution of the Boom Boom (2 Gy x 2) regimen with Big Boom single fraction regimen of only 4 Gy. This report compares our center's experience with Big Boom to Boom-Boom. Materials/Methods All consecutive indolent lymphomas were included. After April 2020 both options of very low dose as well as choice of a standard full dose of 24 Gy were discussed with the patient and choice was made with consideration of access logistics, patient preference as well as disease site(s). Patients were treated with a definitive or palliative intent depending on disease stage and prior therapy exposure. Patients treated with 24 Gy are not included in this report. Overall response rate was assessed with Lugano PET criteria at the initial post-RT imaging. Differences between the two groups were examined using the Fisher's exact test and Mann-Whitney test. Results We evaluated a total of 440 lesions in 363 patients, including 142 lesions (32%) treated with 4 Gy x 1 ("Big Boom") and 298 lesions (67%) treated with 2 Gy x 2 ("Boom Boom"). Table 1 summarizes the patient and treatment characteristics. Patient age at the time of RT, sex, and the proportion of treated lesions with maximum axial diameter of greater than 5 cm were not significantly different between the two groups. Marginal zone lymphoma comprised 27% of each cohort. The Big Boom cohort was more likely to have follicular lymphomas (66% vs 52%, p = 0 .003), though the proportion of higher-grade follicular lymphomas was similar between cohorts. The overall response rate was 87% for both groups at the first post-RT evaluation (median of 2 months from RT for both cohorts). Furthermore, there was no significance difference in the rate of complete response, partial response, stable disease, or progressive disease between the cohorts at initial post-RT imaging. For both regimens, no directly related short-term side effects were observed. Conclusions Both the Big Boom and Boom Boom regimens demonstrated excellent overall response rates at the initial post-RT imaging assessment among patients with indolent lymphomas. While longer term follow-up is required to confirm durability of these findings, our initial experience suggests that the single dose, single visit Big Boom regimen (4 Gy x 1) recommended by ILROG during the Covid-19 pandemic is an effective treatment approach. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Individualized Clinical Target Volume for Irradiation of the Supraclavicular Region in Breast Cancer Based on Mapping of the Involved Ipsilateral Supraclavicular Lymph Nodes

To map supraclavicular fossa-involved lymph nodes (SCF-LNs) in patients with nonmetastatic breast cancer, evaluate the coverage of widely adopted atlases, and propose modified borders for individualized regional irradiation. M0 patients with biopsy-proven SCF-LNs who were SCF treatment-naïve were included. The SCF was spatially divided into subregions, with each node mapped on the original images. The geographic misses after the borders of multiple atlases were evaluated and factors affecting SCF-LNs' spread pattern were analyzed. From 1998 to 2022, 209 patients with 1242 SCF-LNs were eligible. Patients had a median of 4 nodes. At least 537 nodes (43.2%) in 147 patients (70.3%) were lateral to the sternocleidomastoid muscle (SCM), and 403 nodes (32.4%) in 127 patients (60.8%) were dorsal to the anterior scalene muscle (ASM). In the 88 patients with ≤3 SCF-LNs, at least 66 nodes (39.1%) in 40 patients (45.5%) were lateral to the SCM, and 34 nodes (20.1%) in 29 patients (33.0%) were dorsal to the ASM. These nodes were not covered by the Radiation Therapy Oncology Group (RTOG) atlas and partly within the Radiotherapy Comparative Effectiveness atlas. One hundred four patients (49.8%) had 432 SCF-LNs (34.8%) beyond the upper border of the European Society for Radiotherapy and Oncology (ESTRO) atlas. In multivariate regression, nodal sizes were associated with wider spread in the primary group. Being triple-negative (TN) subtype was associated with less spread in the recurrent group. Situation-based clinical target volumes (CTVs) were theorized, in which for a sequential spread, the posterior border could be the posterior scalene muscle or even be more constringent; otherwise, it should touch the anterior trapezius surface. SCF-LNs tend to spread laterally and dorsally beyond the RTOG borders, even in M0 stages with ≤3 SCF-LNs. The ESTRO upper border does not guarantee coverage with multiple SCF-LNs. Nodal burden and non-TN types are predictive of wider dissemination. A situation-based CTV is possibly feasible. Deciphering the SCF-LN spread route is needed.

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.

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.

Factors on development and severity of acute radiodermatitis: prospective single-center study

Aim: Although prior literature has examined the treatment and patient-associated factors affecting the development and severity of acute radiodermatitis, there are relatively few prospective studies evaluating both. This study was prospectively designed to evaluate factors affecting the development and extent of radiation-induced acute skin toxicity called radiodermatitis (RD). &#x0D; Material and Method: A total of 63 patients who underwent radiotherapy (RT) in Ankara Atatürk Research and Education Hospital between July 2017 and October 2018 were evaluated. Patients’ demographic status, disease/treatment details, hemoglobin, ferritin, folic acid, Vit B12, and hemoglobin A1c values were recorded. The development and grade of RD were evaluated weekly by the same radiation oncologist using the Radiation Therapy Oncology Group (RTOG) radiation toxicity guideline.&#x0D; Results: There was no significant relationship between the development of any degree of RD and gender, concomitant chemotherapy (CT), pre-RT CT, comorbid disease, RT technique and blood parameters (Hb, Hba1c, ferritin, folic acid and B12). The development of grade 2-3 RD was significantly affected by the number of operations (p=0.032) and total dose of RT (p=0.008). In patients with grade 2/3 RD, the RT dose at which RD first appeared was 20 Gy (range, 14-36); in patients with grade 1 RD, this value was 32 Gy (range, 16-56) (p=0.018).&#x0D; Conclusion: There is no significant relationship between the development of acute radiodermatitis and Hba1c, hemoglobin, ferritin, B12 and folic acid levels. There was a significant correlation between grade of RD and repeated surgery, increase in total RT dose and early onset of RD.

A Single-Blind, Randomized Controlled Trial of Sanyrene — A Complex of Linoleic Acid and Vitamin E for Prophylaxis of Radiation Dermatitis in Patients with Breast and Head Neck Cancer

<h3>Purpose/Objective(s)</h3> Radiation dermatitis (RD) is a common side effect of radiation therapy (RT). The severity of RD is significantly associated with patients' quality of life (QOL), even negatively affect anticancer efficacy. There is still a lack of consensus on RD prophylaxis and management. Serveal studies reported linoleic acid could reduce incidence rate of skin injury from ultraviolet ray. Here, we investigate the effects of Sanyrene-a complex of linoleic acid and vitamin E versus Vitamin E on RD in patients with breast cancer and head neck cancer receiving radical radiotherapy (≥50Gy). <h3>Materials/Methods</h3> A prospective single-blind, randomized controlled trial was conducted. Patients either received Sanyrene or Vitamin E (usual care). Patients were randomly assigned in 1:1 ratio to receive Sanyrene and Vitamin E. All drugs were topically applied on the area of skin being irradiated at the onset of radiotherapy, twice a day up to 2 weeks post treatment. Radiation therapy oncology group (RTOG) for skin toxicity score and dermatitis-related QOL scale were used to evaluate skin toxicity, pain and skin-related quality of life. The primary endpoint was incidence rate of ≥grade 2 skin toxicity. Secondary endpoint was dermatitis-related QOL. (Trial Registration: ChiCTR2100050910) <h3>Results</h3> A total of 102 patients were randomized in this study. At the end of radiation treatment, Sanyrene arm had a lower percentage of grade 2 (59.2%) and grade 3 (28.7%) skin toxicity compared with Vitamin E arm (84.3% and 41.1%, respectively) (P<0.001). The incidence rate of ≥grade 2 skin toxicity were 2% and 41.9% in Sanyrene arm and 8.2% and 88.8% in Vitamin E arm at day 25 and day 50 during radiation course (HR:0.67, 95%CI:0.472-0.861, P=0.018). Moreover, patients receiving Sanyrene had a 29.4% reduced risk of developing ≥grade 1 skin toxicity throughout treatment compared to Vitamin E arm (HR:0.706, 95%CI:0.581-0.897, P=0.037). Patients in Sanyrene arm reported better scores of dermatitis-related QOL compared to Vitamin E arm at the end of treatment (8.3 vs.25, P=0.013) and 2 weeks post treatment (1.0 vs.22.9, P<0.001). No treatment interruptions and adverse events related to study products were reported in either arm. <h3>Conclusion</h3> Sanyrene is effective for preventing, and delaying the development of any grade skin toxicity. Meanwhile, patients receiving Sanyrene have better dermatitis-related QOL at the end of radiation course.

Can Superficial Parotid Sparing Alone Reduce Xerostomia? A Retrospective Study Correlating Type of Tobacco Use, Chronic Xerostomia and Parotid Sparing

<h3>Purpose/Objective(s)</h3> Head and neck cancer is one of the most common cancers in India. Tobacco chewing is the most widespread form of tobacco consumption. Majority of the patients present in locally advanced stage and achieving parotid sparing with IMRT in these patients can be challenging. We aimed to correlate the incidence of chronic xerostomia with the type of tobacco use and parotid volumes. <h3>Materials/Methods</h3> Patients with squamous carcinomas of head and neck region treated with conventionally fractionated curative-intent radiotherapy (bilateral neck) to a dose of 60-70 Gy between June 2017 and March 2020 were included in the study. The superficial and deep lobes of parotid were contoured retrospectively and the dosimetric data along with physician-assessed Radiation Therapy Oncology Group (RTOG) xerostomia toxicity grades at one year were retrieved. The individual, superficial and deep lobe parotids were considered spared if the mean dose was less than 26Gy. Patients were divided into five groups: Group 1 constituted bilateral parotid-spared, Group 2 of contralateral parotid-spared, Group 3 of contralateral superficial parotid-spared, Group 4 of bilateral superficial parotid-spared, and Group 5 where no sparing could be achieved. The groups were compared using chi-square test. <h3>Results</h3> 174 patients were included in the study. The median age was 59 years (IRQ 20 - 89). Chewing (40%), followed by smoking (35%) were the most frequent forms of tobacco consumption. The most common subsite was oropharynx (30.5%) followed by hypopharynx (26.4%), and about 83% had locally advanced disease. The mean bilateral parotid volume was 55.9 cc (18-130 cc). Tobacco chewers had significantly smaller mean parotid (53cc vs 60cc, p=0.02) and submandibular gland volumes (6cc vs 14cc, p<0.001) as compared to smokers. Bilateral or contralateral parotid sparing was achieved in 62.7%, bilateral or contralateral superficial lobe in 27.6%, and no sparing in 9.8% of patients. At one year, grade 0/I xerostomia was reported by 89.5%, and ≥grade II xerostomia in 11.5%. The grade of xerostomia was similar in smokers and chewers (p=0.95). The ipsilateral (26.5 Gy vs 37.8 Gy, p <0.001) and contralateral (23.3 Gy vs 34.1 Gy, p <0.001) superficial parotid mean dose in patients with grade 0/I and ≥grade II xerostomia was significantly different. Patients with bilateral or contralateral superficial lobe sparing had lower rates of grade II/III xerostomia compared to no sparing group (p<0.001). <h3>Conclusion</h3> Tobacco chewers have smaller parotid and submandibular glands compared to smokers. This did not impact the sparing of glands or the severity of xerostomia. Contralateral or bilateral superficial parotid sparing translated into superior salivary gland function at 1 year.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography–based Lymph Node Atlas for Salvage Radiotherapy in Patients with Recurrent Prostate Cancer: A Validation of the New NRG Oncology 2020 guideline

BackgroundApproximately 20–40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020). ObjectiveTo evaluate and validate the updated NRG 2020 guideline with our established LN atlas. Design, setting, and participantsWe screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients. Outcome measurements and statistical analysisWe evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10–90%), or outside (<10%). Results and limitationsIn comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results. ConclusionsThe updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread. Patient summaryWe compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

Randomized, Multicenter, Phase 3 Study of Accelerated Fraction Radiation Therapy With Concomitant Boost to the Gross Tumor Volume Compared With Conventional Fractionation in Concurrent Chemoradiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer: The Korean Radiation Oncology Group 09-03 Trial

We designed the Korean Radiation Oncology Group 09-03 phase III clinical trial to compare accelerated hypofractionated radiation therapy (RT) using a concomitant boost to the gross tumor volume (GTV) with conventionally fractionated 60-Gy RT in patients with stage III unresectable non-small cell lung cancer (NSCLC). A conventionally fractionated RT group (arm 1; 124 patients) received a 2-Gy daily dose to a total cumulative dose of 44 Gy to the planning target volume (PTV) in 22 fractions and 60 Gy to the GTV in 30 fractions over 6 weeks. A hypofractionated RT group (arm 2; 142 patients) received a 1.8-Gy daily dose to the PTV with a synchronous boost of 0.6 Gy to the GTV, for total cumulative doses of 45 Gy to the PTV and 60 Gy to the GTV in 25 fractions over 5 weeks. All patients received concurrent weekly chemotherapy consisting of paclitaxel and cisplatin. The objective response rate of all patients was 86.5% (arm 1, 84.6%; arm 2, 88.1%; P=.612). The median overall survival was 26 months (arm 1, 26 months; arm 2, 27 months; P=.508). The median progression-free survival was 11 months (arm 1, 10 months; arm 2, 13 months; P=.295). The local tumor control rates at 2 and 5 years were 58.3% and 50.7%, respectively (arm 1, 62.4% and 51.0%, respectively; arm 2, 54.0% and 48.6%, respectively; P=.615). There were no significant between-group differences in the cumulative incidence of grade ≥3 radiation pneumonitis (P=.134) or radiation esophagitis (P=.539). This clinical trial did not confirm the superiority of accelerated 2.4-Gy hypofractionated RT compared with conventional 2-Gy fractionation in patients with unresectable stage III NSCLC undergoing concurrent chemoradiation therapy.

Effects of topical timolol for the prevention of radiation-induced dermatitis in breast cancer: a pilot triple-blind, placebo-controlled trial

IntroductionRadiation therapy is one of the standard methods in the treatment of breast cancer. Radiotherapy-induced dermatitis (RID) is a common complication of radiotherapy (RT) resulting in less tolerance in RT and even discontinuation of treatment. Timolol is a β-adrenergic receptor antagonist that presents the best wound healing effects on both chronic and incurable wound healing. Topical forms of timolol could be effective in the prevention of RID due to the role of β-adrenergic receptors in skin cells and keratinocyte migration, as well as the anti-inflammatory effect of timolol. However, no placebo-controlled randomized trial is available to confirm its role. The current trial aimed to evaluate the efficacy of topical timolol 0.5% (w/w) on the RID severity and patients' quality of life (QOL).MethodPatients aged older than 18 years with positive histology confirmed the diagnosis of invasive and localized breast cancer were included. Patients were randomized based on the random number table to receive each of the interventions of timolol 0.5% (w/w) or placebo topical gels from the first day of initiation of RT and for 6 weeks, a thin layer of gel twice daily. Patients were asked to use a thin layer of gel for at least two hours before and after radiation therapy. Primary outcomes were acute radiation dermatitis (ARD) grade using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and severity of desquamation based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Secondary outcomes were QOL based on Skindex16 (SD-16), maximum grade of ARD, and time of initial RD occurrence.ResultsA total of 64 female patients with an age range of 33 to 79 years were included. The means (SD) of age were 53.88 (11.02) and 54.88 (12.48) in the control and timolol groups, respectively. Considering the RTOG/EORTC and CTCAE scores the difference between groups was insignificant (P-Value = 0.182 and P-Value = 0.182, respectively). In addition, the mean (SD) of time of initial RID occurrence in placebo and timolol groups were 4.09 (0.588) and 4.53 (0.983) weeks, respectively (P-Value = 0.035). The maximum grade of RID over time was significantly lower in the timolol group. During the study period, 75.0% of patients in placebo groups had grade 2 of ARD while in the timolol group it was 31.3% (P-Value = 0.002). QoL was not significantly different between groups (P-Value = 0.148).ConclusionAlthough the topical formulation of timolol, 0.5% (w/w), was found to reduce the average maximum grade of ARD and increase the mean (SD) time of initial RID occurrence, it showed no effect on ARD, severity, and QOL. However, future clinical trials should be performed to assess timolol gel formulation in larger study populations.Trial registrationhttps://irct.ir/ IRCT20190810044500N11 (17/03/2021).

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.

Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation: A Phase 2 Trial of Daily Partial Breast Irradiation

Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled. We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost. All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P=.004), breast pain (P=.004), and physician-reported cosmesis (P < .001). Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

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.