Radiation Therapy Oncology Group Research Articles

Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer

BackgroundWhether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.MethodsWe conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.ResultsA total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P=0.94).ConclusionsFive-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.)

Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial.

This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival. The patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022. Between April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%). For patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.

Well calculated is better than quickly calculated: Comparison of Pencil beam and Monte Carlo algorithms according to the number of lesions and fractionation in radiosurgery of multiple brain metastases

PurposeIn this work we compared pencil beam (PB) and Monte Carlo (MC) algorithms in single isocenter plans of multiple brain metastases radiosurgery (SIMM-SRS) plans using the quality indices reported for SRS. MethodThe plans were evaluated concerning the prescribed dose, fractions and the number of metastases. The quality indices studied were mean dose (Dmean), D95, Paddick conformity index (PCI), Radiation Therapy Oncology Group (RTOG) homogeneity (HIRTOG) and quality of coverage indices (QRTOG), gradient index (GI), efficiency index for targets (Gη12Gy) and organs at risk (OARη12Gy) and V12-V18 for brain. ResultsThe D95 for plans calculated with PB algorithm increased and differences were statistically significant (p < 0.001). For Dmean no differences were observed (p > 0.194). The PCI for the single-fraction cases showed statistical significant differences (p < 0.039). The PCI for the three-fraction cases did not show statistical significant difference (p < 0.569). However, the mean value of the index for all cases did not differ significantly between PB (0.84) and MC (0.81). The GI showed statistically significant differences, only for the plans with more than 10 metastases for a single-fraction (p = 0.0001). The Gη12Gy values reported are within the interval of 0.26–0.80, and for all cases, there were no statistically significant differences. ConclusionConsidering that MC is more accurate for small volumes and heterogeneities, and computational time is reasonable for clinical use, it should be selected in all cases for SIMM-SRS plans. We introduced the potential of novel indices as Gη12Gy, and OARη12Gy for clinical evaluation that potentially serve as optimization factor.

Dosimetric analysis of LAD dose in left-sided breast cancer radiotherapy with deep inspiratory breath hold

Objectives To analyze the dose to the left anterior descending artery (LAD) in patients who have received radiotherapy for left breast cancer with Deep Inspiratory Breath Hold (DIBH) technique and compare it with other cardiac dosimetric parameters, as well as the accepted dose constraints. Materials and Methods 20 patients (10 prospective and 10 retrospective) were selected for this study. All patients underwent 2 non-contrast radiation planning CT scans of 2.5 mm thickness - one with DIBH and one with free breathing. Contouring was done using the Radiation Therapy Oncology Group (RTOG) guidelines. LAD was delineated and given a PRV of 3 mm and 5 mm. Dose-volume histograms (DVH) were used to obtain the data from the approved plans. Results The lung volume receiving 17 Gy in percentage, Dmean of the heart, LAD Dmean and Dmax, and the Dmean and Dmax received by 3 mm and 5 mm PRVs were both very well achieved when compared to the dose constraints given by the DBCG HYPO trial. The study found a higher correlation between the mean heart dose and the 5 mm PRV dose (R2 = 0.81 and 0.71 respectively for the mean and max dose) than the 3 mm PRV, and a positive correlation between the heart dose and LAD making it a useful structure for predicting acute cardiac events. Conclusion The study of 20 patients found that DIBH is effective to minimize cardiac dose and potentially cardiac toxicity, with heart and LAD doses being comparable or lower compared to other studies. The LAD doses recorded were significantly less than those in non-DIBH studies, demonstrating the feasibility of routine contouring and recording LAD dose in left-sided breast radiation patients. Further research is needed to determine the dosimetry and clinical consequences of the Dmean and Dmax of the 5mm PRV to the LAD.

Prevention of radiation induced dermatitis in head and neck cancer patients using cryptomphalus aspersa secretion.

Radiotherapy (RT) is a technique widely used in oncology, acquiring special prominence in head and neck cancer (HNC). RT of HNC may be associated with secondary effects including skin reaction, being dermatitis the most common radio-induced side effect during treatment. The use of a wide variety of agents is reported to handle skin toxicity. The aim of the present work is to evaluate the different level-concentration of Snail Cryptomphalus Aspersa (SCA) that best protect from radiation-induced radiodermatitis in HNC. We performed a single institutional pilot study to assess the skin toxicity with 0%, 5%, 10% and 15% SCA concentration during RT treatment and 1 and 3months after the treatment finished according to the Radiation Therapy Oncology Group (RTOG) scoring. A total of 72 patients with HNC diagnosis who received RT with/without Chemotherapy (Ch) between January of 2018 and June of 2020 were assessed. Radiodermatitis grade was stastistically correlated with the SCA level-concentration and with the influence of extranodal extension status (ENE). A reduction in the rate of grade ≥ II patients' dermatitis was dependent on SCA level-concentration. We found that with higher SCA level-concentration (10 and 15%, patients had 34 and 38% grade ≥ II respectively), this was less than with 0 and 5% SCA level-concentration where a 58% radiodermatitis grade ≥ II was found by Cox regression analysis; p = 0.017 and p = 0.045 respectively. We could conclude that the application of a 10-15% SCA level-concentration after adjusting by ENE, was the best concentration to reduce the rate of grade ≥ II radiodermatitis.

Lung SBRT: Dose gradient optimization based on target size

This study investigated optimization settings that steepen the dose gradient as a function of target size for lung stereotactic body radiation therapy (SBRT). Sixty-eight lung SBRT patients with planning target volumes (PTVs) ranging from 2-203 cc were categorized into small (<20 cc), medium (20-50 cc), and large (>50 cc) groups. VMAT plans were generated using the normal tissue objective (NTO) to penalize the dose gradient at progressively steeper NTO fall-off values (0.1, 0.2, 0.3, 0.4, 0.5 mm-1). Dose was calculated using the AcurosXB algorithm and was normalized so the prescription dose covered 95% of the PTV. Mann-Whitney, Kruskal-Wallis and ANOVA tests were used to assess for statistical differences in the Conformity Index at the 50% isodose level (CI50%), global maximum dose (Dmax), and monitor units (MU) across the various NTO settings. All plans adhered to institutional criteria and met the guidelines of the Radiation Therapy Oncology Group 0813. Steeper NTO fall-off values significantly increased Dmax and MUs across all groups (p < 0.05). CI50% significantly differed with fall-off values in small (0.3 mm-1) and medium (0.2 mm-1) targets, indicating steeper NTO fall-off values improve CI50% for small and medium targets (p < 0.05). Large targets showed no significant CI50% difference across these fall-off values. As target size increases, the importance of fall-off values in achieving an acceptable CI50% diminishes. Smaller targets benefit from steeper fall-off values despite increased Dmax and MUs. Consideration of fall-off value relative to target size is crucial to limit dose spillage outside the target.

Treatment Outcomes and Toxicity Profiles with PORTEC-3 Trial Regimen in South Asian Cohort of High-Risk Endometrial Cancer Patients: A Single-Center Ambispective Analysis

Objectives Adjuvant chemoradiation followed by chemotherapy is the current standard of care in high-risk endometrial cancer after the PORTEC-3 trial. There is a lack of data on this treatment regimen in the South Asian patient cohort. The present study aims to assess toxicity profiles and outcomes in this cohort of patients. Materials and Methods High-risk endometrial cancer patients planned for adjuvant chemoradiation followed by chemotherapy were included. Toxicity was graded using the Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events criteria. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Survival curves were compared using the log-rank test. Cox regression analysis was done to find out the predictors of DFS. Results This study included 58 patients treated from October 2016 to August 2022. Median age was 61 years (interquartile range [IQR] 56–66), with Fédération Internationale de Gynécologie et d'Obstétrique Stages I = 26 (44.8%), II = 5 (8.6%), and III = 27 (46.6%). p53 positivity was seen in 38 (65.5%) patients. Intensity-modulated radiotherapy was used in 44 (79.3%) patients. There was no treatment discontinuation during chemoradiation. Acute Grade 2 and above toxicity during chemoradiation were diarrhea in 10 (17.2%) and hematological in 2 (3.4%). For the planned adjuvant chemotherapy in 55 patients, 51 (92.7%) completed four cycles. Grade 2 or above neuropathy was seen in 11 (20%), with 5 (9%) having persisting neuropathy at 1-year follow-up. At a median follow-up of 31 months, 15 (25.8%) patients recurred; distant = 13 and isolated para-aortic = 2. The median time to recurrence was 16 months (IQR 12–22), with 80% (12 out of 15) of recurrence within the first 2 years of follow-up. The actuarial 5-year DFS and OS were 63.8 and 76.5%, respectively. In univariate analysis, p53 positivity and lymphovascular space invasion were predictors for DFS, with p-values 0.031 and 0.027, respectively. There was no significant predictor identified in multivariate analysis. Conclusion There is good tolerance and compliance to adjuvant chemoradiation and chemotherapy in this South Asian cohort of patients with high-risk endometrial cancer, with no toxicity-related treatment breaks during radiation. The majority of the recurrences were seen at distant sites and within the first 2 years of follow-up. These findings are in line with the outcomes of the PORTEC-3 trial.

Concomitant Boost With Six Fractions of Radiation a Week in Locally Advanced Head and Neck Cancer Patients: A Prospective Study.

Background and objective Radiation therapy plays a significant role in the radical treatment of locally advanced head and neck cancers. Studies have shown theradiobiological advantage of accelerated chemoradiation over conventional chemoradiation as it reduces the chances of accelerated repopulation and decreases overall treatment time. This study aimed to assess the response and toxicities of accelerated concomitant chemoradiation inlocally advanced head and neck cancer patients. Methods A total of 51 patients were enrolled and treated with accelerated concomitant chemoradiation, receiving one fraction of radiation per day, six fractions per week, with the sixth fraction as a boost on Saturdays, with weekly concurrent cisplatin at 40 mg/m2. Patients were followed up till six months after treatment completion. Radiological investigation was done to assess response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.128, and acute toxicities were assessed according to Radiation Therapy Oncology Group (RTOG) criteria. Results The median follow-up period was six months; 28 patients (62.22%) had a complete response and 17(37.78%) had a partial response at six months post-completion of the treatment. The maximum acute toxicities developed at the completion of treatment. Grade III and IV mucositis developed in 14 patients (31.11%) and grade III dermatitis developed in one patient (2.22%), without any grade IV dermatitis during the total duration of treatment. The toxicities were manageable, and most of them resolved after three months of treatment completion. Conclusions Accelerated concomitant chemoradiation with six fractions of radiation in a week led to a decrease in overall treatment time. Of note, 62.22% of patients had complete remission, with manageable acute mucositis and dermatitis, which resolved in 82% and 67%, respectivelywithin three months of treatment completion. However, further studies involving larger samples and longer follow-ups are needed for this regimen to be established as the standard of care in the future.

Hippocampal-Sparing Radiation Therapy in Primary Sinonasal and Cutaneous Tumors of the Head and Neck

Patients with primary sinonasal and cutaneous head and neck (H&N) malignancies often receive meaningful radiation dose to their hippocampi, but this not a classic avoidance structure in radiation planning. We aimed to characterize the feasibility and tradeoffs of hippocampal-sparing radiation therapy (HSRT) for patients with primary sinonasal and cutaneous H&N malignancies. We retrospectively selected patients who were treated definitively for primary sinonasal or cutaneous malignancies of the H&N at an academic medical center. All received (chemo)radiation alone or adjuvantly and substantial radiation dose to 1 or both hippocampi. We created new HSRT plans for each patient with intensity modulated radiation therapy using the original target and organ-at-risk (OAR) volumes. Hippocampi were contoured based on Radiation Therapy Oncology Group guidelines and reviewed by a neuroradiologist. Absolute and relative differences in radiation dose to the hippocampi, planning target volumes (PTVs), and OARs were recorded and compared. There were 18 sinonasal and 12 cutaneous H&N primary tumors (30 patients in total). Median prescription dose was 6600 cGy (range, 5000-7440 cGy), and 14 of the 30 patients received 120 cGy/fraction twice daily, 13 of the 30 patients received 200 cGy/fraction once daily, whereas others received 180-275 cGy/fraction once daily. The relative decrease in ipsilateral hippocampal Dmax and D100% using HSRT was 44% (median, 2009 cGy from 3586 cGy) and 65% (median 434 cGy from 1257 cGy), respectively. There were no statistically significant or clinically meaningful differences in PTV V100%, PTV D1%, or radiation dose to other OARs between HSRT and non-HSRT plans. HSRT is feasible and results in meaningful dose reduction to the hippocampi without reducing PTV coverage or increasing dose to other OARs. We suggest target hippocampal constraints of Dmax < 1600 cGy and D100% < 500 cGy when feasible (without compromising PTV coverage or impacting other critical OARs). The clinical significance of HSRT in patients with primary H&N tumors should be investigated prospectively.

Clinical implementation of real time motion management for prostate SBRT: A radiation therapist’s perspective

Background and purposeThe adoption of hypo-fractionated stereotactic body radiotherapy (SBRT) for treating prostate cancer has led to an increase in specialised techniques for monitoring prostate motion. The aim of this study was to comprehensively review a radiation therapist (RTT) led treatment process in which two such systems were utilised, and present initial findings on their use within a SBRT prostate clinical trial. Materials and Methods18 patients were investigated, nine were fitted with the Micropos RayPilotTM (RP) system (Micropos Medical, Gothenburg, SE) and nine were fitted with the Micropos Raypilot Hypocath TM (HC) system. 36.25 Gray (Gy) was delivered in 5 fractions over 7 days with daily pre- and post-treatment cone beam computed tomography (CBCT) images acquired. Acute toxicity was reported on completion of treatment at six- and 12-weeks post-treatment, using the Radiation Therapy Oncology Group (RTOG) grading system and vertical (Vrt), longitudinal (Lng) and lateral (Lat) transmitter displacements recorded. ResultsA significant difference was found in the Lat displacement between devices (P=0.003). A more consistent bladder volume was reported in the HC group (68.03 cc to 483.7 cc RP, 196.11 cc to 313.85 cc HC). No significant difference was observed in mean dose to the bladder, rectum and bladder dose maximum between the groups. Comparison of the rectal dose maximum between the groups reported a significant result (P=0.09). Comparing displacements with toxicity endpoints identified two significant correlations: Grade 2 Genitourinary (GU) at 6 weeks, P=0.029; and no toxicity, Gastrointestinal (GI) at 12 weeks P=0.013. ConclusionBoth the directly implanted RP device and the urinary catheter-based HC device are capable of real time motion monitoring. Here, the HC system was advantageous in the SBRT prostate workflow.

Increased dicentric chromosome in peripheral lymphocytes is related to acute skin toxicity induced by radiotherapy in cancer patients

ObjectiveTo investigate the impacts of radiotherapy (RT) on dicentric chromosomes in peripheral blood lymphocytes of cancer patients, in order to explore the relationship between dicentric chromosomes and RT-induced adverse reactions. MethodsA total of 33 cancer patients after postoperative RT in a tertiary hospital from October 2021 to May 2022 were enrolled in this study. These patients were grouped according to the grade of acute skin and marrow toxicities determined based on the scoring criteria for acute morbidity developed by the Radiation Therapy Oncology Group (RTOG). Peripheral blood samples were collected from each patient before and after RT, followed by whole-blood lymphocyte culture and chromosome analysis. Dicentric chromosomes were searched automatically using a high-throughput chromosome analysis system and were then confirmed manually. Finally, the relationships of the frequency of dicentric chromosomes (also referred to as the dic frequency) with acute skin and marrow toxicities were assessed. ResultsAfter RT, the mean counts of white blood cells (WBCs), lymphocytes, and platelets significantly decreased, while the red blood cells (RBCs) and hemoglobin notably increased (P ​< ​0.001), while the dic frequency was elevated remarkably, significantly higher in patients with higher-grade (>1) acute skin toxicities compared to those with lower-grade (=1) acute skin toxicities (Z ​= ​−1.985, P ​= ​0.047). However, no significant relationship was observed between the dic frequency and acute marrow toxicity after RT (P ​> ​0.05). Logistic regression showed that radiosensitivity denoted by the post-RT dic frequency in peripheral blood lymphocytes produced insignificant impacts on the severity of RT-induced acute skin toxicities (P ​= ​0.060). ConclusionThe elevated dic frequency in peripheral blood lymphocytes of cancer patients with higher-grade acute skin toxicities suggests enhanced radiosensitivity of peripheral blood lymphocytes, which is associated with the occurrence of RT-induced adverse reactions.

Spatially fractionated radiotherapy (Lattice SFRT) in the palliative treatment of locally advanced bulky unresectable head and neck cancer

ObjectivesLocally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. MethodsPatients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2–3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39–79 years), and the median tumor volume was 208 cc (cc) (range 48–701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. ConclusionsLattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.

Acute radiation skin injury in stage III-IV head and neck cancer: scale correlates and predictive model

PurposeActive radiation skin injury (ARSI) has the highest incidence of acute adverse reactions caused by radiotherapy (RT) in patients with head and neck cancer (HNC). This study aimed to screen risk factors that can facilitate the identification of HNC patients at high risk of ARSI.MethodsData from 255 stage III-IV HNC patients who underwent intensity-modulated radiation therapy (IMRT) were collected. The data from our medical records, including clinical characteristics and hematological indices before RT, were retrospectively collected and arranged. The Common Terminology Criteria for Adverse Events Criteria (CTCAE), Radiation Therapy Oncology Group Criteria (RTOG), World Health Organization Criteria (WHO), Oncology Nursing Society (ONS), Acute Radiation Dermatitis Graduation Scale, Douglas & Fowler and Radiation Dermatitis Severity Scale (RDSS) were used to assess ARSI. Of these, CTCAE was used for further analysis. Binary logistic regression analyses were used to identity risk factors. To establish the correction between each risk factor and the ARSI score, the odds ratio (OR) and 95% confidence interval (CI) were computed.ResultsThe assessment results of the CTCAE with RTOG, WHO, ONS, Graduation Scale, Douglas & Fowler and RDSS have good consistency. After radiotherapy, 18.4% of patients had at least 3 (3 +) grade ARSI. Multivariate logistic regression analysis revealed that the KPS score, blood glucose level, white blood cell count, and plasma free thyroxine (FT4) concentration were independent risk factors for 3 + grade ARSI. A nomogram was constructed on the basis of these risk factors, which demonstrated good predictive power according to the area under the ROC curve (AUC). The satisfactory consistency and clinical efficacy of the nomogram were confirmed by calibration curves and decision curve analysis (DCA).ConclusionA low KPS score, high blood glucose level, high white blood cell count, and high thyroid hormone prior to radiotherapy for stage III-IV HNC are independent risk factors for grade 3 + RSI.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

BackgroundTherapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking.MethodsTrans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses.DiscussionThe SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research.Trial registrationanzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Multi-institutional investigation into the robustness of intra-cranial multi-target stereotactic radiosurgery plans to patient setup errors

PurposeThis study aimed to analyse correlations between planning factors including plan geometry and plan complexity with robustness to patient setup errors. MethodsMultiple-target brain stereotactic radiosurgery (SRS) plans were obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets with a 20 Gy prescription. Setup error was simulated using an in-house tool. Dose to targets was assessed via dose covering 99 % (D99 %) of gross tumour volume (GTV) and 98 % of planning target volume (PTV). Dose to organs at risk was assessed using volume of normal brain receiving 12 Gy and maximum dose covering 0.03 cc of brainstem. Plan complexity was assessed via edge metric, modulation complexity score, mean multi-leaf collimator (MLC) gap, mean MLC speed and plan modulation. ResultsEven for small (0.5 mm/°) errors, GTV D99 % was reduced by up to 20 %. The strongest correlation was found between lower complexity plans (larger mean MLC gap and lower edge metric) and higher robustness to setup error. Lower complexity plans had 1 %–20 % fewer targets/scenarios with GTV D99 % falling below the specified tolerance threshold. These complexity metrics correlated with 100 % isodose volume sphericity and dose conformity, though similar conformity was achievable with a range of complexities. ConclusionsA higher level of importance should be directed towards plan complexity when considering plan robustness. It is recommended when planning multi-target SRS, larger MLC gaps and lower MLC aperture irregularity be considered during plan optimisation due to higher robustness should patient positioning errors occur.

Efficacy and safety of low-dose celecoxib with chemoradiation in locally advanced head-and-neck squamous cell carcinoma

Background: Head-and-neck squamous cell carcinoma (HNSCC) is a major cancer in India with a poor prognosis. Novel antineoplastic agents, such as selective cyclooxygenase-2 inhibitors such as celecoxib, have shown antitumor, anti-angiogenesis, and radiosensitizing effects, improving radiotherapy response in many cancers. Aims and Objectives: This study aimed to determine the efficacy and safety of low-dose celecoxib combined with concurrent chemoradiation in Locally Advanced HNSCC. Materials and Methods: A double-arm prospective randomized control study was conducted, in which 103 eligible locally advanced HNSCC patients were randomized to concurrent chemoradiotherapy 66 Gy/2 Gy/33 fractions/61/2 weeks along with Inj Cisplatin 40 mg/m2 weekly either with celecoxib 100 mg twice daily (Study Arm – 62) or placebo (Control Arm – 41). Tumor response was evaluated using response evaluation criteria in solid tumors criteria 1.1 and acute toxicities based on the radiation therapy oncology group and common terminology criteria for adverse events criteria 5.0. Results: On analysis using the Chi-square test, the complete response rate was 65.6% in the study arm compared to 44.7% in the control arm, with P=0.0441 (significant at P&lt;0.05). The incidence of acute dermatitis and mucositis (grade ≥3) in the study and control arms was 29.3% versus 23.6%, with P=0.544 and 40% versus 37% with a P=0.782 (insignificant at P&lt;0.05), respectively. The patients in both arms were followed up to assess late toxicities, locoregional control rate, disease-free survival, and overall survival. Conclusion: Adding low-dose daily celecoxib to concurrent chemoradiation with weekly cisplatin in locally advanced HNSCC significantly improved the clinical response rates with acceptable treatment-related toxicities.

Hypofractionated versus Conventional Postmastectomy Irradiation for Breast Cancer: Comparison of Acute Skin Toxicity.

Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors. This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot. Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P < 0.001), and tumor bed planning target volume (PTV-TB) (P = 0.002) were significantly correlated with higher rates of acute skin toxicity. Hypofractionated WBI demonstrated similar acute skin adverse reactions compared to conventional WBI. These findings indicate that hypofractionated radiotherapy offers comparable tolerance, equivalent curative effect, convenience, andeconomic benefits, supporting its clinicalpromotion.

Palliating hematologic oncologic emergencies with radiation in the age of targeted systemic therapies: three illustrative cases.

Hematologic oncologic emergencies with an urgent indication for radiation are a relatively routine occurrence for the radiation oncologist. As patients are living longer and have multiple treatment options for their relapsed or refractory diseases, it is important that palliative treatments avoid precluding patients from or delaying next-line potentially curative treatments wherever possible. We highlight the following experiences from our clinical practice: newly diagnosed plasma cell disease causing cord compression; life threatening cutaneous lymphoma with tumors covering the majority of the body surface area; and relapsed/refractory diffuse large B-cell lymphoma (DLBCL) requiring bridging radiation to a mass impinging on the brachial plexus combined with chimeric antigen receptor (CAR)-T cell therapy. In each case, urgent palliative radiation was utilized, but the approaches were nuanced, with careful consideration of subsequent potential therapies and how the current course of radiation should be tailored for the best interplay with the overall treatment course and trajectory of the disease. With the rapid development of new therapies, it can be difficult to stay up to date on the most recent practice guidelines. Drawing on hematologic-specific guidelines, such as those provided by the International Lymphoma Radiation Oncology Group, and disease site experts can aid in ensuring patients are appropriately palliated and eligible for future therapies.

Impact of dose volume parameters and clinical characteristics on radiation-induced acute oral mucositis for head and neck cancer patients treated with carbon-ion radiotherapy dose volume outcome analysis.

To assess the predictive value of different dosimetric parameters for acute radiation oral mucositis (ROM) in head and neck cancer (HNCs) patients treated with carbon-ion radiotherapy (CIRT). 44patients with HNCs treated with CIRT were evaluated for acute ROM which was defined as severe when the score ≥3 (acute ROM was scored prospectively using the Radiation Therapy Oncology Group (RTOG) score system). Predictive dosimetric factors were identified by using univariate and multivariate analysis. Male gender, weight loss >5%, and total dose/fractions were related factors to severe ROM. In multivariate analysis, grade ≥3 ROM was significantly related to the Dmax, D10, D15, and D20 (P < 0.05, respectively). As the receiver operating characteristics (ROC) curve shows, the area under the curve (AUC) for D10 was 0.77 (p = 0.003), and the cutoff value was 51.06 Gy (RBE); The AUC for D15 was 0.75 (p = 0.006), and the cutoff value was 42.82 Gy (RBE); The AUC for D20 was 0.74 (p = 0.009), and the cutoff value was 30.45 Gy (RBE); The AUC for Dmax was 0.81 (p < 0.001), and the cutoff value was 69.33 Gy (RBE). Male gender, weight loss, and total dose/fractions were significantly association with ROM. Dmax, D10, D15 and D20 were identified as the most valuable predictor and we suggest aDmax limit of 69.33 Gy (RBE), D10 limit of 51.06 Gy (RBE), D15 limit of 42.82 Gy (RBE), and D20 limit of 30.45 Gy (RBE) and for oral mucosa.

Sparing the Hippocampus in Prophylactic Cranial Irradiation Using Three Different Linear Accelerators: A Comparative Study.

Hippocampus protection, as an organ at risk in brain radiotherapy, might protect patients' quality of life. Prophylactic cranial irradiation (PCI) has been used traditionally in small cell lung cancer (SCLC) patients as it increases survival. This study aimed to discover the contributing parameters for a successful PCI with simultaneous protection of the hippocampus by using three different treatment machines. For this purpose, treatment plans were generated for 45 SCLC patients using three half-arcs in three linear accelerators (LINACs; Elekta Infinity, Synergy, and Axesse; Elekta Ltd, Stockholm, Sweden) with different radiation field sizes and multileaf collimator (MLC) leaf thickness characteristics. The prescribed dose was 25 Gy in 10 fractions. Thresholds for the hippocampus were calculated based on the Radiation Therapy Oncology Group 0933 dose constraints. The planning and treatment system templates were common to all three LINACs. Plan evaluation was based on the dosimetric target coverage by the 95% isodose, the maximum dose of the plan, the conformity index (CI), the degree of plan modulation (MOD), and the patient-specific quality assurance (QA) pass rate. The mean target coverage was highest for Infinity (97.3%), followed by Axesse (96.6%) and Synergy (95.5%). The mean maximum dose was higher for Synergy (27.5 Gy), followed by Infinity (27.0 Gy) and Axesse (26.9 Gy). Axesse plans had the highest CI (0.93), followed by Infinity (0.91) and Synergy (0.88). Plan MOD was lower for Synergy (2.88) compared with Infinity (3.07) and Axesse (3.69). Finally, patient-specific QA was successful in all Infinity plans, in all but one Synergy plan, and in 17/45 Axesse plans, as was expected from the field size in that treatment unit. Based on overall performance, the most favorable combination of target coverage, hippocampus sparing, and plan deliverability was obtained with the LINAC, which has the largest field opening and thinnest MLC leaves.