BACKGROUND: Recently, the PORT-C and LUNG-ART trials, which evaluated the role of postoperative radiation therapy (PORT), have significantly altered the treatment landscape for NSCLC pN2 patients who previously underwent surgery. In response, the Italian Association of Radiotherapy and Oncology Thoracic Oncology study group has initiated an observational multicenter trial to assess both acute and late toxicities of PORT in pN2 NSCLC patients treated with modern techniques.
METHODS: Data on NSCLC patients submitted to PORT after radical surgery treated between 2015 and 2020 in six Italian Centers were collected. Heart, lung, and esophageal acute and late toxicities have been retrospectively analyzed and related to radiation therapy dosimetric parameters. Furthermore, loco-regional control, distant metastasis and overall survival have been analyzed.
RESULTS: A total of 212 patients with a median age of 68 years from six different centers were included in this analysis (142 males and 70 females). Prior to undergoing PORT, 96 patients (45.8%) had a history of heart disease, 110 patients (51.9%) had hypertension, and 51 patients (24%) had COPD. Acute toxicity was observed in 147 patients (69.3%), with lung toxicity occurring in 93 patients (G1 in 70 patients, G2 in 17 patients, and G3 in 4 patients), esophageal toxicity in 114 patients (G1 in 89 patients, G2 in 23 patients, and G3 in 1 patient), and cardiac toxicity in 4 patients (G1 in 2 patients and G3 in 2 patients). Late side effects were found in 60 patients (28.3%), predominantly involving the lungs (51 patients: 32 G1, 11 G2, and 1 G3) and the esophagus (11 patients: 8 G1 and 3 G2), with no reported late cardiac side effects. Various clinical and dosimetric parameters were found to correlate with both acute and chronic toxicities. Over a median follow-up period of 54 months, 48 patients (22.6%) showed locoregional disease relapse, 106 patients (50%) developed distant metastases, and 66 patients (31.1%) died.
CONCLUSIONS: RAC-TAC retrospective multicentric study showed the low toxicity of PORT when advanced technology is used. At the same time, it\'s noteworthy to underline that 50% of the patients develop distant recurrences in the follow up.

BACKGROUND: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT.
METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement.
RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years.
CONCLUSIONS: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

Introduction: With the evolution of radiotherapy techniques and a better understanding of clinicopathological factors, we aimed to evaluate the treatment effect of post-operative radiotherapy (PORT) and associated predictive factors in patients with completely resected pN2 stage III non-small cell lung cancer (R0 pN2-stage III NSCLC). Material and Method: The cancer registration database of a single medical center was searched for R0 pN2-stage III NSCLC. Clinicopathological factors and information about post-operative therapies, including PORT and adjuvant systemic treatment, were retrospectively collected and analyzed. The Kaplan-Meier method and a Cox regression model were applied for time-to-event analysis, with disease-free survival (DFS) being the primary outcome. Results: From 2010 to 2021, 82 R0 pN2-stage III NSCLC patients were evaluated, with 70.1% of tumors harboring epidermal growth factor receptor mutations (EGFR mut.). PORT was performed in 73.2% of cases, and the median dose was 54 Gy. After a median follow-up of 42 months, the 3-year DFS and overall survival (OS) rates were 40.6% and 77.3%, respectively. Distant metastasis (DM) was the main failure pattern. In the overall cohort, DFS was improved with PORT (3-year DFS: 44.9% vs. 29.8%; HR: 0.552, p = 0.045). Positive predictive factors for PORT benefit, including EGFR mut., negative extranodal extension, positive lymphovascular invasion, 1-3 positive lymph nodes, and a positive-to-dissected lymph node ratio ≤0.22, were recognized. OS improvement was also observed in subgroups with less lymph node burden. Conclusions: For R0 pN2-stage III NSCLC, PORT prolongs DFS and OS in selected patients. Further studies on predictive factors and the development of nomograms guiding the application of PORT are highly warranted, aiming to enhance the personalization of lung cancer treatment.

OBJECTIVE: Although postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC.
METHODS: This study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan-Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability.
RESULTS: Of all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85-0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93-1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85-1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94-1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98-1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99-1.23, P = 0.07).
CONCLUSIONS: PORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

OBJECTIVE: Shortening the overall radiation therapy (RT) treatment time has advantages in cost and treatment burden, but data on hypofractionated RT in head and neck squamous cell carcinoma are limited. This study assessed the safety of moderately hypofractionated RT in the postoperative setting.
METHODS: Patients with completely resected stage I-IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with intermediate risk factor(s) including T3/4 disease, positive lymph node(s), close margin(s), perineural invasion, and/or lymphovascular invasion were enrolled on a rolling 6-design phase 1 study. Levels 0 and 1 consisted of 46.5 Gy in 15 fractions delivered 5 days a week and 44.4 Gy in 12 fractions delivered 4 days a week, respectively. The primary endpoint was maximum tolerated dose/fractionation of moderately hypofractionated postoperative RT.
RESULTS: Twelve patients were enrolled with 6 each on levels 0 and 1. No patient experienced a dose-limiting toxicity or grade 4 to 5 toxicity. Acute grade 3 toxicity occurred in 2 patients on level 0 (weight loss, neck abscess) and 3 patients on level 1 (all oral mucositis). One patient on level 0 experienced late grade 3 toxicity (persistent neck abscess). With a median follow-up of 18.6 months, 2 patients on level 1 had a recurrence: a regional recurrence in the undissected, unirradiated contralateral neck from a well-lateralized tonsil primary and an in-field local recurrence of oral tongue primary. The maximum tolerated dose/fractionation was determined to be 44.4 Gy in 12 fractions, but owing to more favorable tolerability in the setting of equivalent biologically effective dose, 46.5 Gy in 15 fractions was deemed the recommended phase 2 dose/fractionation.
CONCLUSIONS: Moderately hypofractionated RT delivered over 3 weeks is well tolerated in the short term in this phase 1 cohort of patients with head and neck squamous cell carcinoma following surgical resection. The follow-up phase 2 randomized trial will deliver 46.5 Gy in 15 fractions as the experimental arm.

OBJECTIVE: Most patients with resected brain metastases receive post-operative radiotherapy. This study investigated outcomes of fractionated stereotactic radiotherapy (FSRT) alone or whole-brain irradiation plus simultaneous integrated boost (WBI+SIB) in the post-operative setting.
METHODS: Forty-four patients receiving FSRT alone (n=32) or WBI+SIB (n=12) after resection of 1-3 brain metastases from 2014-2022 were analyzed. Twelve factors were evaluated for local control (LC), distant brain control (DBC), and overall survival (OS).
RESULTS: On univariate and multivariate analyses, single brain metastasis was associated with improved LC and DBC. Longer interval between tumor diagnosis and radiotherapy, single brain metastasis, and Karnofsky performance score >80 were associated with improved OS. WBI+SIB showed a trend towards better DBC.
CONCLUSIONS: Several independent predictors of outcomes after FSRT or WBI+SIB following resection of brain metastases were identified. Given similar survival in the post-operative setting between FSRT and WBI+SIB, potential toxicity remains a significant factor in treatment recommendations.

The role of postoperative radiotherapy (PORT) in patients with resected locally advanced non-small-cell lung cancer (NSCLC) remains controversial due to the radiation techniques used in randomized trials. We conducted a retrospective cohort study evaluating contemporary PORT techniques to evaluate the safety of PORT and risk of death from intercurrent disease .
We analyzed consecutive patients with NSCLC treated in a single center that underwent PORT for pN2 disease and/or positive margin, with 3-dimensional conformal radiotherapy (3DRT), intensity modulated radiotherapy , or proton RT (PRT), between 2008 and 2019. Clinical details were collected including intercurrent deaths, defined as death without cancer recurrence. Kaplan-Meier and Cox-Proportional Hazards Models were used.
Of 119 patients, 21 (17.6%) received 3DRT, 47 (39.5%) intensity modulated radiotherapy, and 51 (42.9%) PRT. Median follow-up was 40 months (range 8-136) and median RT dose was 5040cGy. Most patients (65.5%) received sequential adjuvant chemoRT; 18.5% received concurrent chemoRT. The rate of grade 3 toxicities was 9.2%. There were 13 (10.9%) deaths from intercurrent diseases, including 6 from second primary cancers and 2 from cardiopulmonary diseases. There were 2 additional deaths from cardiopulmonary disease in patients with cancer progression at time of death. Mean, V5Gy, V30Gy heart doses and mean lung doses were significantly lower with PRT. Three-year OS and disease-free-survival were 70.1% and 49.9%.
PORT using contemporary techniques was well tolerated with acceptable toxicity and low rates of intercurrent deaths. Proton therapy significantly reduced heart and lung doses, but radiotherapy modality was not associated with differences in intercurrent disease.

BACKGROUND: Delays in commencing post-operative radiation therapy (PORT) and prolongation of overall treatment times (OTT) are associated with reduced overall survival and higher recurrence rates in patients with head and neck squamous cell carcinoma (HNSCC). The objective of this study was to evaluate treatment delays, factors contributing to those delays and to explore strategies to mitigate them.
METHODS: This retrospective study included patients with mucosal HNSCC at Townsville University Hospital treated with curative intent surgery and PORT between June 2011 and June 2019. The proportion of patients who experienced delays in commencing PORT (>6 weeks) and OTT were evaluated and reasons for these delays were explored.
RESULTS: The study included 94 patients of which 70% experienced PORT delay. Surgery at an external facility (81% vs 56%, P = 0.006) and longer post-operative length of stay (P = 0.011) were significantly associated with a higher incidence of PORT delay. Aboriginal and Torres Strait Islander patients had a higher rate of PORT delay (89% vs 68.2%, P = 0.198). Significant delays were noted from time of surgery to radiation oncology (RO) consult and from RO consult to commencement of radiation treatment.
CONCLUSIONS: This study demonstrates that the prevalence of PORT delay for patients with HNSCC remains high with room for improvement. Potential strategies to improve delays include developing effective care coordination, addressing specific needs of Indigenous patients, implementing reliable automated tracking and communication systems between teams and harnessing existing electronic referral systems.

OBJECTIVE: To evaluate the impact of moderately hypofractionated postoperative radiotherapy (RT) in prostate cancer (PCa).
METHODS: The data of 304 surgically resected PCa patients were analyzed. One hundred and five patients underwent adjuvant RT (aRT), 77 early-savage RT (esRT), and 123 salvage RT (sRT). Biochemical relapse-free survival (BRFS), progression-free survival (PFS) and toxicity were analyzed. A propensity score matching (PSM) was performed to account for potential confounders between aRT and esRT groups.
RESULTS: The median follow-up was 33 months. Three-year BRFS and PFS were 82 and 85.2%, respectively, in the overall population. At the multivariate analysis, Gleason score and hormone therapy were factors independently correlated with BRFS and PFS. After PSM, there was no difference in BRFS and PFS between aRT and esRT patients. Severe toxicity was represented by grade 3 urinary incontinence (3.5%) and urgency (1%), and aRT correlated with increased any-grade acute toxicity. Severe grade 3 gastrointestinal late toxicity occurred in 1.3% of cases.
CONCLUSIONS: Postoperative moderately hypofractionated RT achieved acceptable disease control rate and demonstrated no increased or unexpected toxicity. Future prospective studies should evaluate the role of postoperative RT in patients with unfavorable disease characteristics.

Lymph node ratio (LNR) has been increasingly reported as a prognostic factor in oral cavity squamous cell carcinoma (OCSCC). This study aimed to develop and validate a prognostic nomogram integrating LNR and to further assess its role in guiding adjuvant therapy for OCSCC.
A total of 8703 OCSCC patients treated primarily with surgery in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and randomly divided into training and validation cohorts. The nomogram was created based on the factors identified by Cox model. The value of PORT and chemotherapy was respectively evaluated in each prognostic group according to nomogram-deduced individualized score.
The final nomogram included tumor site, grade, T stage, number of positive lymph nodes and LNR. Calibration plots demonstrated a good match between predicted and observed rates of overall survival (OS). The concordance indexes for training and validation cohorts were 0.720 (95% confidence interval (CI): 0.708, 0.732) and 0.711 (95% CI: 0.687, 0.735), both significantly higher than did TNM stage (p< 0.001). According to individualized nomogram score, patients were stratified into three subgroups with significantly distinct outcome. PORT presented survival benefit among medium- and high-risk groups whereas a near-detrimental effect in low-risk group. Chemotherapy was found to be beneficial only in high-risk group.
This LNR-incorporated nomogram surpassed the conventional TNM stage in predicting prognosis of patients with non-metastatic OCSCC and identified sub-settings that could gain survival benefit from adjuvant thearpy.