RTOG 0915-compliant patient specific QA for lung stereotactic body radiotherapy using the new PTW 1600SRS detector array.

PURPOSE: An area of focus in radiotherapy is the treatment of oligometastatic lung cancer using highly conformal techniques such as SBRT, performed using VMAT that involves flattening filter free (FFF) beams. This study proposes a new calibration procedure for PTW Octavius 1600SRS detector array and was designed to also evaluate clinical and dosimetric aspects of a patient-specific quality assurance (PSQA) for lung SBRT patients. METHODS: The cohort consists of 20 patients, treated for lung metastases using SBRT with 50 Gy dose in 5 fractions (10 Gy/fr). The proposed calibration method uses only one calibration factor determined at maximum dose rate of 6MV FFF photon beam. The dosimetric accuracy of achieving a high dose gradient was analyzed using the RTOG 0915 protocol and was confirmed by PSQA procedures using the PTW Octavius 1600SRS detector. RESULTS: Conformity index, gradient index, maximum dose at 2 cm and V20 parameters were evaluated with clinical favorable results, with only two plans with lesions situated in the inferior lobe exceeding the deviation allowed for the gradient index. Gamma passing rates using the new calibration method were 98.93% and 99.38% for different gamma criteria of 2 mm/2% and 1 mm/3%, respectively. CONCLUSIONS: The proposed method for calibration using one calibration factor at maximum dose rate for the involved photon beam shows clinically acceptable gamma passing rates. Employing the RTOG 0915 protocol for lung SBRT treatment plan evaluation brings important dosimetric information about treatment plan quality and dose gradient fall-off which can be correlated with the results achieved during the pretreatment verification procedures.

Comparative Analysis of Dosimetry: IMRT versus 3DCRT in Left-Sided Breast Cancer Patients with Considering Some Organs in Out - of - Field Borders.

Purpose: The local management approach for node-positive breast cancer has undergone substantial evolution. Consequently, there exists a pressing need to enhance our treatment strategies by placing greater emphasis on planning and dosimetric factors, given the availability of more conformal techniques and delineation criteria, achieving optimal goals of radiotherapy treatment. The primary aim of this article is to discuss how the extent of regional nodal coverage influences the choice between IMRT and 3D radiation therapy for patients. Patients and Methods: A total of 15 patients diagnosed with left breast cancer with disease involved lymph nodes were included in this study. Delivering the recommended dose required the use of a linear accelerator (LINAC) with photon beams energy of 6 mega voltage (6MV). Each patient had full breast radiation using two planning procedures: intensity-modulated radiotherapy (IMRT) and three-dimensional radiotherapy (3D conformal). Following the guidelines set forth by the Radiation Therapy Oncology Group (RTOG), the planned treatment coverage was carefully designed to fall between 95% and 107% of the recommended dose. Additionally, Dose Volume Histograms (DVHs) were generated the dose distribution within these anatomical contours. Results and Conclusion: The DVH parameters were subjected to a comparative analysis, focusing on the doses absorbed by both Organs at Risk (OARs) and the Planning Target Volume (PTV). The findings suggest that low doses in IMRT plan might raise the risk of adverse oncological outcomes or potentially result in an increased incidence of subsequent malignancies. Consequently, the adoption of inverse IMRT remains limited, and the decision to opt for this therapy should be reserved for situations where it is genuinely necessary to uphold a satisfactory quality of life. Additionally, this approach helps in reducing the likelihood of developing thyroid problems and mitigates the risk of injuries to the supraclavicular area and the proximal head of the humerus bone.

Effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy.

Objective: To find out the effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy. Methods: This was a retrospective study. Sixty six patients with nasopharyngeal carcinoma who received radiotherapy in the Affiliated Hospital of Hebei University from March 2021 to March 2022 were included and randomly divided into the observation group and the control group, with 33 cases in each group. Patients in the control group were given conventional care measures, while those in the observation group were given psychological support intervention on top of conventional care measures. The nursing effects between the two groups were compared. Results: After the intervention, the psychological resilience score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). The psychological resilience scores after the intervention were significantly higher in the observation group than before the intervention, and those in the control group were higher than before the intervention, with a statistically significant difference(P<0.05). The overall health score of quality of life in the observation group was significantly higher than that in the control group after the intervention, with a statistically significant difference(P<0.05). Moreover, the skin reaction in the observation group after radiotherapy was significantly better than that of the control group (P<0.01). Conclusion: Psychological support intervention is an effective means to treat patients with nasopharyngeal carcinoma, which results in various benefits such as improving patients' mental resilience and quality of life and reducing the incidence of adverse reactions after radiotherapy.

Reirradiation in head and neck squamous cell carcinoma; prognostic indicators, oncologic and functional outcomes.

OBJECTIVES: Patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) have a poor prognosis and limited therapeutic alternatives. While reirradiation is feasible, it is usually associated with high treatment toxicity and is not yet considered the standard of care. Based on current NCCN guidelines, in the context of very advanced head and neck cancer (recurrent and/or persistent disease), surgical intervention is explored initially with/without adjuvants while unresectable disease is approached with radiation and/or systemic therapies. Specific and reliable prognostic indicators for both -oncologic and functional outcomes- have yet to be defined for this population. METHODS: Retrospective chart review of 54 patients treated with reirradiation at a tertiary academic institution between January of 1998 and January of 2024. Only patients with non-metastatic recurrent, and second primary HNSCC were included in the series. Demographics, staging, radiation dose and technique, additional therapy, histopathologic variables, EORTC toxicity, pre- and post-treatment PEG/tracheotomy dependency and oncologic outcomes were retrieved. RESULTS: The study cohort consisted of 54 patients (37 males, 17 females) with HNSCC, averaging 62.7 years in age. Initial tumors were locally advanced in over 42 % of cases, with 58 % being node-negative. The head and cutaneous regions (24.5 %) and tongue (20.8 %) were the most common tumor sites. Primary surgical resection and adjuvant radiation were performed in 47.2 % of cases, and concurrent chemotherapy was used in 40.7 %. Reirradiation was mainly for local or regional recurrence (88.9 %), often following salvage surgery (68.5 %), with a mean dose of 5623 Gy over 52.5 fractions. Positive surgical margins were present in 29.4 % of cases, and extracapsular spread in 59.5 %. No significant differences were found between the salvage surgery and definitive reirradiation groups except for tumor site (P = 0.022). Median follow-up was 52.6 months, with 27 deaths reported. Lymphovascular invasion was significantly correlated with overall survival (P = 0.017), while initial tumor T-stage and neck disease involvement were linked to local-regional control (P = 0.030 and P = 0.033, respectively). Reirradiation increased tracheotomy and PEG-tube dependency by 20 % (P = 0.011) and 23 % (P = 0.003), respectively. CONCLUSIONS: Reirradiation is a feasible therapeutic alternative in recurrent head and neck SCC. Oncologic outcomes observed in this series compare favorably to most published reports. Complete response and perineural invasion were independent prognostic factors for survival and locoregional control. While no mortality directly associated with treatment was observed in this series, reirradiation had a significant impact in functional outcomes in terms of increased risk of tracheotomy and peg tube dependency. Further studies are required to define the role of this treatment in head and neck cancer.

Patient-reported outcomes (PROs) in NRG Oncology RTOG 0436: a phase III trial evaluating the addition of cetuximab to paclitaxel, cisplatin, and radiation for esophageal cancer treated without surgery.

PURPOSE/OBJECTIVES: NRG/RTOG 0436 evaluated cetuximab added to chemoradiation (CRT) for non-operative esophageal cancer management. PRO objectives assessed improvement in the FACT-Esophageal cancer subscale (ECS), version 4, with cetuximab, and if improved ECS correlated with clinical complete response (cCR). MATERIALS/METHODS: Patients were randomized to cisplatin/paclitaxel/radiation ± cetuximab. Overall survival (OS) was the primary endpoint, with a 420 patient target, which also provided 82% power to detect ≥ 15 increase in the proportion of cetuximab patients with ECS improvement from baseline to 6-8 weeks post-CRT; α = 0.05, using a χ2 test. Improvement in ECS and its Swallowing and Eating Indices (SI, EI) was defined as 5, 4 and 2 point increases, respectively, from baseline to 6-8 weeks post-CRT. Univariate logistic regression assessed if cCR was associated with improved ECS. RESULTS: This study was stopped early for not meeting a pre-specified OS endpoint and did not show survival benefit. Of 420 planned patients, 344 enrolled and 281 consented to PROs. ECS was completed by 261 (93%) at baseline, 173 (66%) 6-8 weeks post-CRT, and 117 (64%) at 1 year. At 6-8 weeks, patients receiving CRT + Cetuximab didn't have improved ECS; they experienced a lower proportion of improvement compared to standard CRT (37% vs. 53%; P = 0.04). The proportion of CRT patients with improvement in SI was 9% higher than with cetuximab, but not statistically significant (39% vs. 30%, P = 0.22). There was no association between treatment and EI. When examining ECS scores at 1 year by cCR vs. residual disease, a higher proportion of cCR patients improved, but not statistically significant (48% vs. 45%, P = 0.74). CONCLUSIONS: The addition of cetuximab to CRT for the nonoperative management of esophageal cancer did not improve PROs.

Radiation Therapy Oncology Group 8502 "QUAD shot" regimen using volumetric modulated arc therapy for incurable head and neck cancer.

OBJECTIVES: We aimed to evaluate the outcomes of the Radiation Therapy Oncology Group 8502 "QUAD shot" regimen using volumetric modulated arc therapy (VMAT) for incurable head and neck cancer (HNC). MATERIALS AND METHODS: We included 105 patients with HNC in the study, undergoing at least one QUAD shot regimen cycle. We planned the radiotherapy using VMAT with 6 MV photons. One QUAD shot cycle included 14.8 Gy in 4 fractions with at least 6-hour intervals over 2 consecutive days, repeated every 3-6 weeks up to 3 cycles. RESULTS: We completed 1, 2, and 3 cycles in 11 (10 %), 17 (16 %), and 77 (73 %) patients, respectively. We concurrently performed systemic therapy in 13 (12 %) patients. Tumor response was observed in 92 (88 %) patients and at least one symptom relief in 51 (71 %) of 72 patients. We observed an overall response (tumor response or symptom relief) in 98 (93 %) patients with all patients who completed 3 cycles achieving it. The median overall survival (OS) was 6.8 months. Our multivariate analysis revealed that non-squamous cell carcinoma (p < 0.001), T category of 0-2 (p = 0.021), and 3 QUAD shot cycles (p < 0.001) were independent prognostic factors of better OS. We observed Grade 3 toxicity in 2 (2 %) patients while no ≥ Grade 4 acute or ≥ Grade 3 late toxicity. CONCLUSIONS: The QUAD shot regimen using VMAT exerts appropriate palliative effect in patients with incurable HNC. Treatment with higher QUAD shot cycle number would be recommended for better treatment outcomes.

A dosimetric comparative study following RTOG and ESTRO contouring guidelines for breast radiation therapy.

PURPOSE: To compare the dosimetric parameters considering the Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) guidelines for breast cancer radiotherapy. Two radiotherapy techniques, intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT), were considered. PATIENTS AND METHODS: Twenty-eight patients with left-sided medially-located TanyN2M0 tumors were contoured based on RTOG and ESTRO guidelines. 9-field IMRT, 10-field IMRT, 11-field IMRT, and VMAT treatment plans were applied as radiotherapy (RT) techniques for both contouring sets. The dosimetric parameters of the RT plans were extracted and compared. RESULTS: Comparing dose-volume histogram (DVH) parameters, equivalent uniform dose (EUD), and normal tissue complication probability (NTCP) of OARs across the contouring guidelines and considering each RT technique showed that the only significant differences were higher Dmax, Dmean, V30, and V45, EUD, and NTCP of the thyroid in all treatment modalities when the RTOG guideline had been adopted. Using the VMAT technique, PTV's EUD and the tumor control probability (TCP) were considerably higher when the ESTRO guideline was adopted. Moreover, the conformity index (CI) of VMAT plans was significantly higher when the ESTRO guideline was used. CONCLUSION: Unless having higher doses to thyroid when the RTOG guideline was adopted, the doses to other organs-at-risk (OAR) were similar between the two considering guidelines. Moreover, except for higher EUD, TCP, and CI for VMAT when the ESTRO guideline was used, no other significant differences were obtained between dosimetric parameters of target volumes considering the RT techniques and contouring guidelines.

Effect of melatonin cream on acute radiation dermatitis in patients with primary breast cancer: A double-blind, randomized, placebo-controlled trial.

AIM: This was a double-blind, placebo-controlled randomized study investigating whether melatonin can protect against radiation dermatitis in women receiving radiation therapy for primary breast cancer. METHODS: Patients were included before radiation therapy and followed once weekly throughout treatment with a 3-week follow-up. Patients applied 1 g of cream to the irradiated skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or placebo. Our outcomes were the Radiation Therapy Oncology Group's (RTOG) acute radiation morbidity scoring criteria for skin, a pixel analysis of erythema in clinical photographs, and patients' use of corticosteroid cream. Outcomes were evaluated once weekly throughout the trial. The primary outcomes were RTOG-score and pixel analysis at 2 weeks follow-up. Secondary outcomes were the use of corticosteroid cream and analyses of RTOG-scores and pixel analyses throughout the trial. RESULTS: Sixty-five patients were included, 17 dropped out, totaling 26 and 22 patients randomized to melatonin and placebo, respectively. RTOG-scores and pixel analyses at 2 weeks follow-up showed no difference p = .441 and p = .890, respectively). There was no difference in the use of corticosteroid cream (p = .055). Using logistic regression, the melatonin group had a higher likelihood of having a low RTOG-score (p = .0016). The logistic regression showed no difference between the groups for the pixel analyses. CONCLUSION: Our primary outcome showed no difference in RTOG-scores at 2 weeks follow-up, however, the RTOG-score over the entire duration of the study demonstrated a protective effect of melatonin. Further studies are warranted investigating higher doses of melatonin, and whether corticosteroids may influence the effect of melatonin cream against radiation dermatitis.

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Current Trends in Neurosurgical Management of Adult Diffuse Low-Grade Gliomas in Canada.

There is considerable variability in the management of diffuse low-grade gliomas (LGGs). To characterize treatment paradigms, a survey of Canadian neurosurgeons was performed with forty neurosurgeons responding. Their responses show that the management of patients with LGGs has evolved in the past decade and findings from the RTOG9802 trial have been integrated into the practice of Canadian neurosurgeons. Most respondents stated that the patient selection and treatment strategy advocated by the RTOG9802 trial needs further evaluation. Overall, there is a trend toward more aggressive surgical resections, and future investigations will have to more accurately stratify patient risk profiles.

Current and Future Frontiers of Molecularly Defined Oligodendrogliomas.

Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.

Effect of Nano-Curcumin on Radiotherapy-Induced Skin Reaction in Breast Cancer Patients: A Randomized, Triple-Blind, Placebo-Controlled Trial.

PURPOSE: Despite advances in medical technology, radiation-induced dermatitis occurs in 95% of cancer patients receiving radiation therapy. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The aim of this study was to determine the efficacy of nano-curcumin in alleviating the radiation-induced skin reactions (RISRs) in breast cancer patients. METHODS: A randomized, triple-blinded, placebo-controlled clinical trial was performed on 42 patients with breast cancer. The patients were randomly allocated to receive radiotherapy plus placebo (control group) and radiotherapy plus 80 mg/day nano-curcumin capsules (treatment group) up to two weeks after the end of treatment. Then, the RISRs (graded by the radiation therapy oncology group (RTOG) scale) and pain level of the patients were evaluated at baseline and weekly. Finally, the results were analyzed by T-test and Pearson chi-square test. RESULTS: According to the RTOG scale, 0%, 14.28%, and 85.71% of patients in the control group showed grades 0, 1, and 2 RISRs, respectively. In the treatment group, it was observed that 9.52%, 47.61%, and 42.85% of patients had grades 0, 1, and 2 RISRs, respectively. Compared to the control group, it was found that concomitant use of the nano-curcumin supplement did not significantly reduce the RISR severity during the first to sixth weeks (P > 0.05); however, there was a significant difference at week 7 (P = 0.01). Moreover, the patient-reported pain, as the secondary endpoint, was significantly reduced in the treatment group compared with the control group (P < 0.05). CONCLUSIONS: In general, it was found that the administration of nano-curcumin could alleviate radiation- induced skin toxicity of breast cancer patients, but this effect was not significant.

The Learning Curve and Inter-Observer Variability in Contouring the Hippocampus under the Hippocampal Sparing Guidelines of Radiation Therapy Oncology Group 0933.

Hippocampal-sparing brain radiotherapy (HS-BRT) in cancer patients results in preservation of neurocognitive function after brain RT which can contribute to patients' quality of life (QoL). The crucial element in HS-BRT treatment planning is appropriate contouring of the hippocampus. Ten doctors delineated the left and right hippocampus (LH and RH, respectively) on 10 patients' virtual axial images of brain CT fused with T1-enhanced MRI (1 mm) according to the RTOG 0933 atlas recommendations. Variations in the spatial localization of the structure were described in three directions: right-left (X), cranio-caudal (Y), and forward-backward (Z). Discrepancies concerned three-dimensional localization, shape, volume and size of the hippocampus. The largest differences were observed in the first three delineated cases which were characterized by larger hippocampal volumes than the remaining seven cases. The volumes of LH of more than half of hippocampus contours were marginally bigger than those of RH. Most differences in delineation of the hippocampus were observed in the area of the posterior horn of the lateral ventricle. Conversely, a large number of hippocampal contours overlapped near the brainstem and the anterior horn of the lateral ventricle. The most problematic area of hippocampal contouring is the posterior horn of the lateral ventricle. Training in the manual contouring of the hippocampus during HS-BRT treatment planning under the supervision of experienced radiation oncologists is necessary to achieve optimal outcomes. This would result in superior outcomes of HS-BRT treatment and improvement in QoL of patients compared to without HS-BRT procedure. Correct delineation of the hippocampus is problematic. This study demonstrates difficulties in HS-BRT treatment planning and highlights critical points during hippocampus delineation.

Adjuvant Chemoradiotherapy in Resected Pancreatic Ductal Adenocarcinoma: Where Does the Benefit Lie? A Nomogram for Risk Stratification and Patient Selection.

INTRODUCTION: The impact of adjuvant sequential chemoradiotherapy (CRT) on survival in resected pancreatic ductal adenocarcinoma (PDAC) remains unclear and warrants further investigation. METHODS: NCDB patients with R0/R1 resected PDAC who received adjuvant chemotherapy without CRT or followed by CRT per RTOG-0848 protocol were included. Cox regression for 5-year overall survival (OS) was performed and used to construct a pathologic nomogram in patients who did not receive CRT. A risk score was calculated and patients were divided into low-risk and high-risk groups. Patients from each risk stratum were matched for the receipt of CRT to assess the added benefit of CRT on survival. The Kaplan-Meier analysis was performed to compare OS. RESULTS: A total of 7146 patients were selected, 1308 (18.3%) received CRT per RTOG-0848. Cox regression concluded grade, T stage, N stage, node yield < 12, R1, and LVI as significant predictors of 5-year OS which were used to construct the risk score. Matched analysis in low-risk patients (score 0-79) showed no difference in OS between CRT vs. no CRT (47.6 ± 5.7 vs. 45.1 ± 3.9 months; p = 0.847). OS benefit was 3% at 1 year, - 4% at 2 years, and 4% at 5 years. In high-risk patients (score 80-100), median OS was higher in CRT vs. no CRT (24.8 ± 0.7 vs. 21.7 ± 0.8 months; p = 0.043). Absolute OS benefit was 13% at 1 year, 5% at 2 years, and - 1% at 5 years. CONCLUSION: CRT has a short-lived impact on OS in resected PDAC that is only evident in high-risk patients. In this subset, survival benefit peaks at 1 year and subsides at 3 to 5 years following PDAC resection.

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life.

AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.

Evaluation of Automated Treatment Planning and Organ Dose Prediction for Lung Stereotactic Body Radiotherapy.

PURPOSES: To evaluate whether the auto-planning (AP) module can achieve clinically acceptable treatment plans for lung stereotactic body radiotherapy (SBRT) and to evaluate the effectiveness of a dose prediction model. METHODS: Twenty lung SBRT cases planned manually with 50 Gy in five fractions were replanned using the Pinnacle (Philips Radiation Oncology Systems, Fitchburg, WI) AP module according to the dose constraint tables from the Radiation Therapy Oncology Group (RTOG) 0813 protocol. Doses to the organs at risk (OAR) were compared between the manual and AP plans. Using a dose prediction model from a commercial product, PlanIQ (Sun Nuclear Corporation, Melbourne, FL), we also compared OAR doses from AP plans with predicted doses. RESULTS: All manual and AP plans achieved clinically required dose coverage to the target volumes. The AP plans achieved equal or better OAR sparing when compared to the manual plans, most noticeable in the maximum doses of the spinal cord, ipsilateral brachial plexus, esophagus, and trachea. Predicted doses to the heart, esophagus, and trachea were highly correlated with the doses of these OARs from the AP plans with the highest correlation coefficient of 0.911, 0.823, and 0.803, respectively. CONCLUSION: Auto-planning for lung SBRT improved OAR sparing while keeping the same dose coverage to the tumor. The dose prediction model can provide useful planning dose guidance.

RTOG-0129 risk groups are reproducible in a prospective multicenter heterogeneously treated cohort.

BACKGROUND: Recursive partitioning analysis (RPA) from the Radiation Therapy Oncology Group (RTOG)-0129 has identified a low-risk group of patients with oropharynx cancer (OPC) who might benefit from therapeutic de-intensification. These risk groups have not yet been reproduced in an independent cohort treated heterogeneously. Therefore, the objective of this analysis was to validate the RPA risk groups and examine the prognostic impact of novel factors. METHODS: Patients with OPC were enrolled in a prospective study at 3 academic medical centers from 2013 to 2018. Medical record abstraction was used to ascertain clinical variables including staging and survival according to the 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Human papillomavirus-positive tumor status was determined by p16 immunohistochemistry and/or HPV RNA in situ hybridization. Kaplan-Meier and log-rank methods were used to compare survival. Cox proportional hazards were used to generate univariate and multivariable hazard ratios (HRs). RESULTS: Median follow-up time was 3.2 years. The low-, intermediate-, and high-risk groups had significant differences in 2-year overall survival (OS, 99.1%; 95% CI, 94.4%-99.9% vs OS, 93.0%; 95% CI, 74.7%-98.2% vs OS, 80.0%; 95% CI, 40.9%-94.6%; Poverall = .0001) and 2-year progression-free survival (PFS, 97.5%; 95% CI, 92.4%-99.2% vs PFS, 89.3%; 95% CI, 70.3%-96.4% vs PFS, 80.0%; 95% CI, 40.9%-94.6%; Poverall < .002). After adjustment for age, sex, and level of educational attainment, OS and PFS were significantly lower for the intermediate- (OS adjusted hazard ratio [aHR], 5.0; 95% CI, 1.0-23.0; PFS aHR, 3.4; 95% CI, 1.0-11.5), and high- (OS aHR, 7.3; 95% CI, 1.4-39; PFS aHR, 5.0; 95% CI, 1.2-21.6) risk groups compared with the low-risk group. Lower education was also independently significantly associated with worse OS (aHR, 8.9; 95% CI, 1.8-44.3) and PFS (aHR, 3.1; 95% CI, 1.0-9.6). CONCLUSIONS: In patients with OPC, the RTOG-0129 RPA model is associated with OS and PFS in a heterogeneously treated cohort.

DIBH-IMRT for RTOG 1304, Cancer of the left breast: A case study.

The purpose of this case study is to describe an external beam radiation therapy planning technique for carcinoma of the left breast. A female patient on protocol NSABP B-51/RTOG 1304 presented with unusual anatomy and large habitus. Deep inspiration breath-hold (DIBH) IMRT was used in conjunction a DIBH-3D conformal radiotherapy (3DCRT) tangential boost plan to meet the dose criteria for protocol compliance. Traditionally 3DCRT planning using a DIBH technique would be used for both billing authorization and as DIBH-IMRT involves a longer treatment time and more difficulty in terms of patient compliance; however, the patient tolerated the treatment very well. The subsequent treatment plan met all criteria per protocol with the exception of the ipsilateral lung, which passed with acceptable variation.

Inter-clinician delineation variation for a new highly-conformal flank target volume in children with renal tumors: A SIOP-Renal Tumor Study Group international multicenter exercise.

BACKGROUND AND PURPOSE: Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance. MATERIALS AND METHODS: Six pediatric renal cancer cases were transferred to ten radiation oncologists from seven European countries ('participants'). These participants delineated the pre- and postoperative Gross Tumor Volume (GTVpre/post), and Clinical Target Volume (CTV) during two test phases (case 1-2 and 3-4), followed by guideline refinement and a quality assurance phase (case 5-6). Reference target volumes (TVref) were established by three experienced radiation oncologists. The Dice Similarity Coefficient between the reference and participants (DSCref/part) was calculated per case. Delineations of case 5-6 were graded by four independent reviewers as 'per protocol' (0-4 mm), 'minor deviation' (5-9 mm) or 'major deviation' (≥10 mm) from the delineation guideline using 18 standardized criteria. Also, a major deviation resulting in underestimation of the CTVref was regarded as an unacceptable variation. RESULTS: A total of 57/60 delineation sets were completed. The median DSCref/part for the CTV was 0.55 without improvement after sequential cases (case 3-4 vs. case 5-6: p = 0.15). For case 5-6, a major deviation was found for 5/18, 12/17, 18/18 and 4/9 collected delineations of the GTVpre, GTVpost, CTV-T and CTV-N, respectively. An unacceptable variation from the CTVref was found for 7/9 participants for case 5 and 6/9 participants for case 6. CONCLUSION: This international multicenter delineation exercise demonstrates that the new consensus for highly-conformal postoperative flank target volume delineation leads to geometrical variation among participants. Moreover, standardized review showed an unacceptable delineation variation in the majority of the participants. These findings strongly suggest the need for additional training and centralized pre-treatment review when this target volume delineation approach is implemented on a larger scale.

Evolution of the Role of Radiotherapy for Anal Cancer.

Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.