Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

How Has Prostate Cancer Radiotherapy Changed in Italy between 2004 and 2011? An Analysis of the National Patterns-Of-Practice (POP) Database by the Uro-Oncology Study Group of the Italian Society of Radiotherapy and Clinical Oncology (AIRO).

BACKGROUND AND PURPOSE: Two previous "Patterns Of Practice" surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a "benchmark" Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. METHODS: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. RESULTS: More than 50% of POP III patients were classified as low or intermediate risk using D'Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy. CONCLUSIONS: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004-2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT-allowing for tighter margins-would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies.

Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas.

OBJECTIVES: To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. METHODS: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I-IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit. RESULTS: Among 45 consecutively enrolled patients with a median age of 68 years (range 22-86), 26 (58%) were female. Thirty-one patients (69%) with a stage I-II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. CONCLUSIONS: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. ADVANCES IN KNOWLEDGE: This study shows the efficacy of LDRT in the treatment of MALT and MZL.

An external validation of the Candiolo nomogram in a cohort of prostate cancer patients treated by external-beam radiotherapy.

BACKGROUND: the aim of this study is to perform an external validation for the Candiolo nomogram, a predictive algorithm of biochemical and clinical recurrences in prostate cancer patients treated by radical Radiotherapy, published in 2016 on the journal "Radiation Oncology". METHODS: 561 patients, treated by Radiotherapy with curative intent between 2003 and 2012, were classified according to the five risk-classes of the Candiolo nomogram and the three risk-classes of the D'Amico classification for comparison. Patients were treated with a mean prostatic dose of 77.7 Gy and a combined treatment with Androgen-Deprivation-Therapy in 76% of cases. The end-points of the study were biochemical-progression-free-survival (bPFS) and clinical-Progression-Free-Survival (cPFS). With a median follow-up of 50 months, 56 patients (10%) had a biochemical relapse, and 30 patients (5.4%) a clinical progression. The cases were divided according to D'Amico in low-risk 21%, intermediate 40%, high-risk 39%; according to Candiolo very-low-risk 24%, low 37%, intermediate 24%, high 10%, very-high-risk 5%. Statistically, the Kaplan-Meier survival curves were processed and compared using Log-Rank tests and Harrell-C concordance index. RESULTS: The 5-year bPFS for the Candiolo risk-classes range between 98 and 38%, and the 5-year cPFS between 98 and 50% for very-low and very-high-risk, respectively. The Candiolo nomogram is highly significant for the stratification of both bPFS and cPFS (P < 0.0001), as well as the D'Amico classification (P = 0.004 and P = 0.001, respectively). For the Candiolo nomogram, the C indexes for bPFS and cPFS are 75 and 80%, respectively, while for D'Amico classification they are 64 and 69%, respectively. The Candiolo nomogram can identify a greater number of patients with low and very-low-risk prostate cancer (61% versus 21% according to D'Amico) and it better picks out patients with high and very-high-risk of recurrence, equal to only 15% of the total cases but subject to 48% (27/56) of biochemical relapses and 63% (19/30) of clinical progressions. CONCLUSIONS: the external validation of the Candiolo nomogram was overall successful with C indexes approximately 10% higher than the D'Amico control classification for bPFS and cPFS. Therefore, its clinical use is justified in prostate cancer patients before radical Radiotherapy. Trial registration Retrospectively registered.

Adoption of Expansion Margins to Reduce the Dose Received by the Coronary Arteries and the Risk of Cardiovascular Events in Lymphoma Patients.

PURPOSE: Mediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit. METHODS AND MATERIALS: Forty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (Dmax), median (Dmed), and mean (Dmean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications. RESULTS: Plan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in Dmax, Dmed, and Dmean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV. CONCLUSIONS: Integration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.

Role of Radiotherapy in Post-transplant Lymphoproliferative Disorders: Three Case Reports and Review of the Literature.

Post-transplant lymphoproliferative disorder (PTLD) is an aggressive malignancy that occurs in patients who have undergone solid organ transplantation or hematopoietic stem cell transplantation. It develops as the result of uncontrolled cell proliferations owing to reduced immunological surveillance. PTLD may occur with a various spectrum of clinical presentations, including both localized and extensive disease. Management can be significantly variable according both to the clinical presentation and to the histologic features. The most important systemic treatment strategies are reduction of immunosuppressive therapy, chemotherapy, anti B-cell antibodies, especially rituximab and cytokine-based therapies. The localized form of PTLD could be efficiently treated, and potentially cured, with surgery or radiotherapy (RT). Involved site RT may be a feasible effective option for the treatment of patients with PTLD, given the excellent radio-sensitivity of lymphoid disorders. In this report, we describe 3 adult patients with PTLD treated with moderate-dose RT (24-36 Gy) having a good local control with negligible toxicity. We also review the literature data on the role of radiation therapy in this particular setting.

Ocular Complications After Radiation Therapy: An Observational Study.

AIM OF THE STUDY: The study aims to quantify the incidence of ocular complications in patients irradiated on the head and neck area in our medical center, stratified by type of neoplasm and radiation dose received. MATERIALS AND METHODS: From an existing database of patients radio-treated in our center, we selected 25 patients irradiated in the 2011-2018 period. The patients had been treated for orbital lymphoma, nasopharyngeal carcinoma and cranial base meningioma. The selected patients received an ophthalmologic evaluation which included a complete ophthalmological and orthoptic assessment. RESULTS: Our results showed a significantly higher incidence of DES (dry eye syndrome) and corneal complications for eyes receiving a Dmax higher than 40 Gy, as well as for cataract incidence in eyes that had received a Dmax to the lens higher than 5 Gy. We found an overall thinning of the RNFL (retinal nerve fiber layer) in eyes that had received a Dmax higher than 50 Gy, as well as a greater MD (mean deviation) from normal visual field values. CONCLUSION: In conclusion, we can say that the study confirms the presence of a correlation between the received radiation dose and the onset of eye complications, despite the small sample.

Automatic genetic planning for volumetric modulated arc therapy: A large multi-centre validation for prostate cancer.

PURPOSE: The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual). METHODS: Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning. RESULTS: For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D15% and Dmean were reduced by 8.1% and 17.9%, bladder D25% and Dmean by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable. CONCLUSION: A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning.

68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy.

OBJECTIVES: The primary objective is to assess the efficacy of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in hormone-sensitive prostate cancer (PCa). Secondary objectives are (1) to evaluate changes in clinical management; (2) to determine which covariates independently predict positive scan; (3) to assess 68Ga-PSMA-11-PET/CT performance in different settings of PSA relapse. MATERIALS AND METHODS: Inclusion criteria include (1) histologically diagnosed PCa; (2) previous radical therapy; (3) proven biochemical recurrence (BCR) or biochemical persistence (BCP); (4) hormone-sensitive PCa (HSPC); (5) androgen deprivation therapy (ADT)-free for at least 6 months; (6) PSA < 1.5 ng/mL or any PSA in case of negative choline-PET/CT (n = 38). Changes in clinical management were defined by multidisciplinary tumour-board. Clinical settings were BCP (group-1, n = 25); first-time BCR (group-2, n = 121); BCR after salvage therapy (group-3, n = 77). RESULTS: Two hundred twenty-three (223) consecutive patients were enrolled: median PSA = 0.65 ng/mL (0.2-8.9) and median PSAdt = 9.3 months (0.4-144.6). 96.9% received RP as primary therapy. 68Ga-PSMA-11-PET/CT positivity rate was 39.9% (CI95% 33.5-46.7%). Disease confined to pelvis was detected in 23.3% of cases. At least one distant lesion was observed in 16.6% of cases. Secondary objectives are as follows: (1) changes in clinical management were observed in 34.5% of patients; (2) PSA, PSAdt and T stage > 3a were independent predictors (all p < 0.03); (3) 68Ga-PSMA-11-PET/CT positivity rate was 56% (in group 1, 36.3% in group 2, 40.3% in group 3. CONCLUSION: This study attested the overall good performance of 68Ga-PSMA-11-PET/CT to detect PCa locations in HSPC patients eligible for salvage therapy, influencing the therapy management in 35.4% of cases. Furthermore, patient characteristics are influencing factors of 68Ga-PSMA-11-PET/CT positivity rate and should be considered to reduce false negative scan.

Radiation therapy for oligometastatic oropharyngeal cancer.

At presentation, isolated metastasis from oropharyngeal squamous cell carcinoma is rare. Liver is a relatively uncommon first site of failure, especially in the absence of other distant metastases, particularly without diagnosis of lung metastases. We report on a case of HPV-related oropharyngeal squamous cell carcinoma with synchronous liver metastasis treated with radiation therapy. This condition, defined as "oligometastatic state," describes a subset of patients with limited volume metastatic disease in whom favorable outcomes were reported with the use of local ablative therapies on both the primary tumor and metastatic sites. As a definitive treatment, we offered the patient, ineligible for other therapeutic approaches, exclusive radiation treatment on the head and neck region and a stereotactic ablative approach targeted to the liver metastasis.

Inclusion of heart substructures in the optimization process of volumetric modulated arc therapy techniques may reduce the risk of heart disease in Hodgkin's lymphoma patients.

BACKGROUND AND PURPOSE: Radiotherapy is an effective treatment for Hodgkin's lymphoma (HL), but increases the risk of long term complications as cardiac events and second cancers. This study aimed to reduce the risk of cardiovascular events through an optimization of the dose distribution on heart substructures in mediastinal HL patients with the adoption of different volumetric modulated arc therapy (VMAT) techniques, while maintaining the same risk of second cancer induction on lungs and breasts. MATERIALS AND METHODS: Thirty patients (15 males and 15 females, 15 bulky lesions) treated between 2012 and 2017 at our institution were selected. Disease extent was mediastinum plus neck (n = 10), mediastinum plus unilateral axilla (n = 10) and mediastinum alone (n = 10). Lungs, breasts, whole heart and sub-structures (coronary arteries, valves and chambers) were contoured as organs at risk and included in the optimization process. A "first-generation" multi-arc butterfly VMAT (B-VMAT) planning solution was compared to a full-arc butterfly VMAT (FaB-VMAT) approach, consisting of a full arc plus a non-coplanar arc. Lifetime attributable risk (LAR) of second breast and lung cancer and relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. RESULTS: FaB-VMAT resulted in lower mean dose to whole heart (7.6 vs 6.9 Gy, p = 0.003), all coronary arteries (16.1 vs 13.5 Gy, p < 0.001), left ventricle (4.2 vs 3.4 Gy, p = 0.007) and in lower V20Gy to the lungs (15% vs 14%, p = 0.008). A significant lower RR for CAD and CHF was observed for FaB-VMAT. The risk of second breast and lung cancer was comparable between the two solutions, with the exception of female patients with mediastinal bulky involvement, where B-VMAT resulted in lower mean dose (2.8 vs 3.5 Gy, p = 0.03) and V4Gy (22% vs 16%, 0.04) to breasts, with a significant reduction in LAR (p = 0.03). CONCLUSIONS: FaB-VMAT significantly decreased the RR for CAD and CHF compared to B-VMAT, with almost the same overall risk of lung and breast cancer induction. These results are influenced by the different anatomical presentations, supporting the need for an individualized approach.

Plan optimization for mediastinal radiotherapy: Estimation of coronary arteries motion with ECG-gated cardiac imaging and creation of compensatory expansion margins.

BACKGROUND AND PURPOSE: Inadvertent heart and coronary arteries (CA) irradiation may increase the risk of coronary artery disease (CAD) in patients receiving thoracic irradiation. To date, the entity of cardiac-related CA displacement and the possible margins to be used for planning organs at risk volume (PRV) have been poorly described. Aim of this study was to quantify CA displacement and to estimate PRV through the use of ECG-gated computed tomography (CT) scans. MATERIAL AND METHODS: Eight patients received an ECG-gated intravenous contrast enhanced CT for non-cancer related reasons. Nine data sets were reconstructed over the entire R-R cycle with a dedicated retrospective algorithm and the following structures were delineated: Left main trunk (LM), left anterior descending (LAD), left circumflex (CX) and right coronary artery (RCA). CA displacements across the different cardiac phases were evaluated in left-right (X), cranio-caudal (Y) and anteroposterior (Z) directions using the McKenzie-van Herk formula (1.3 * Σ + 0.5 * σ). RESULTS: The following CA displacements were found in X, Y and Z coordinates: 3.6, 2.7 and 2.7 mm for LMT, respectively; 2.6, 5.0 and 6.8 mm for LAD, respectively; 3.5, 4.5 and 3.7 mm for CX, respectively; 3.6, 4.6 and 6.9 mm for RCA, respectively. Based on the mean displacements, we created a PRV of 3 mm for LM, 4 mm for CX and 5 mm for LAD and RCA. CONCLUSION: CA showed relevant displacements over the heart cycle, suggesting the need for a specific PRV margin to accurately estimate the dose received by these structures and optimize the planning process.

De-escalation of breast radiotherapy after conserving surgery in low-risk early breast cancer patients.

The reduction in the burden related to treatment is becoming more and more important in modern oncology. Radiation therapy is a mainstay option in the postoperative setting for early breast cancer patients after breast-conserving surgery. Nowadays, different options are available to de-escalate radiotherapy in this scenario such as the use of hypofractionated whole-breast radiation, the selective delivery of the boost dose to the lumpectomy cavity, the introduction of accelerated partial breast irradiation and the omission of treatment in appropriately selected patients with low-risk features. We herein provide a review article on this topic.

Volumetric modulated arc therapy (VMAT) to deliver nodal irradiation in breast cancer patients.

To evaluate feasibility, safety, toxicity profile and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver regional nodal irradiation (RNI) after either mastectomy or breast conservation (BCS) in high-risk breast cancer patients. Between January 2015 and January 2017, a total of 45 patients were treated with VMAT to deliver RNI together with whole breast or post-mastectomy radiotherapy. The fractionation schedule comprised 50 Gy in 25 fractions given to supraclavicular and axillary apex nodes and to whole breast (after BCS) or chest wall (after mastectomy). Two opposite 50°-60° width arcs were employed for breast ad chest wall irradiation, while a single VMAT arc was used for nodal treatment. Treatment was generally well tolerated. Acute skin toxicity was G2 in 13.3% of patients. Late skin toxicity consisted of G1 induration/fibrosis in six patients (13.3%) and G2 in 1 (2.2%). Dosimetric results were consistent in terms of both target coverage and normal tissue sparing. In conclusion, VMAT proved to be a feasible, safe and effective strategy to deliver RNI in breast cancer patients after either BCS or mastectomy with promising dosimetric results and a mild toxicity profile.

No differences in radiological changes after 3D conformal vs VMAT-based stereotactic radiotherapy for early stage non-small cell lung cancer.

OBJECTIVE: To compare patterns of acute and late radiological lung injury following either 3D conformal or image-guided volumetric modulated arc therapy stereotactic radiotherapy for Stage I non-small-cell lung cancer. METHODS: We included 148 patients from a prospective mono-institutional stereotactic body radiation therapy (SBRT) series (time interval 2004-2014), treated with prescription BED10 Gy (at 80%) in the range 100-120 Gy. The first 95 patients (2004-2010) were planned with 3D-CRT, with a stereotactic body frame. The second cohort (2010-2014) included 53 patients, planned with volumetric IMRT on a smaller planning target volume generated from a patient's specific internal target volume, with a frameless approach through cone-beam CT guidance. Acute and late radiological modifications were scored based on modified Kimura's and Koenig's classifications, respectively. RESULTS: Median follow-up time was 20.5 months. The incidence of acute radiological changes was superimposable between the groups: increased density was observed in 68.4 and 64.2% of patients for 3D-CRT and VMAT, respectively, and patchy ground glass opacity in 23.7 and 24.5%, respectively; diffuse ground glass opacity was 2.6 vs 9.4%, respectively, and patchy consolidation 2.6 vs 1.9%, respectively. Late changes occurred in approximately 60% of patients: modified conventional pattern was the most frequent modification (25 vs 32.6%, respectively); other patterns were less common (mass-like 19.6 vs 17.4%, and scar-like 13 vs 10.9%, respectively). CONCLUSION: Results of the present study indicate that the pattern of radiological lung changes following SBRT for peripheral early stage non-small-cell lung cancer is not influenced by the different techniques used for planning and delivery. Advances in knowledge: This comparative observational study shows that smaller margins, image guidance and most importantly dose distribution do not change the pattern of radiological injury after lung SBRT; the same scoring system can be used, and expected incidence is similar.

Risk stratification system and pattern of relapse in patients treated with adjuvant radiotherapy after radical prostatectomy.

PURPOSE: To retrospectively evaluate the role of adjuvant radiotherapy (ART) as monotherapy in a cohort of prostate cancer patients with undetectable prostate-specific antigen (PSA) after surgery and to propose a risk stratification system. METHODS: Between 2003 and 2010, 174 consecutive patients were treated with ART (median dose 71 Gy) at a single institution. Subsequently, we assigned a score of 1 to the following risk factors (RF): T stage ≥3b, presurgical PSA ≥10 ng/mL, pathologic Gleason score (GS) ≥4 + 3, and positive surgical margin (R1). The scores were then summed to stratify the population into low risk (LR), intermediate risk (IR), and high risk (HR). RESULTS: Median follow-up was 61 months (range 4-105). Five-year biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and overall survival (OS) were respectively 93%, 97.1%, and 98.6%. On univariate analyses, GS was the only variable related to bRFS (p = 0.04) and to cRFS (p = 0.05). Any variable was related to OS. Kaplan-Meier analysis showed that HR patients (3-4 RF) had a worse bRFS (p = 0.02) compared to LR patients (0 RF or R1 as single RF); IR patients (1-2 RF) had a lower bRFS compared to LR patients (p = 0.06). Patients with R1 as single RF have the same bRFS as patients with 0 RF (p = 0.6) and are considered as LR patients. CONCLUSIONS: Adjuvant radiotherapy leads to excellent bRFS and cRFS rates at 5 years (93.3% and 97.1%, respectively) in our population. Patients with multiple RF are at higher risk of bRFS. Patients with R1 as single RF have bRFS rates comparable to patients without any RF.

Three-dimensional ultrasound-based image-guided hypofractionated radiotherapy for intermediate-risk prostate cancer: results of a consecutive case series.

External beam radiotherapy (EBRT) is a standard of care in the treatment of prostate cancer. Hypofractionation is a valid option either radiobiologically and logistically in this context. Image-guidance procedures are strongly needed to provide ballistic precision to radiation delivery. The Clarity platform allows for the acquisition of three-dimensional ultrasound scans (3D-US) to perform image-guided radiotherapy. We treated a consecutive series of intermediate-risk prostate cancer patients (according to NCCN stratification) with a hypofractionated schedule (70.2 Gy/26 fractions at 2.7 Gy/daily to the prostate gland excluding the seminal vesicles at 62.1 Gy) under 3D-US guidance with the Clarity platform. The 3-year biochemical-relapse-free survival, distant-metastases-free, cancer-specific and overall survival were 98.6% (CI: 91.1-99.6%), 98.6% (CI: 91.1-99.6%), 97.5% (CI: 94.5-99.1%), and 94.3% (CI: 90.4-96.7%), respectively. Maximum detected acute GU toxicity was G0 in 22 patients (29.7%), G1 in 30 (22.7%), G2 in 19 (25.6%), G3 in 3 (4%). Maximum detected acute GI toxicity at the end of EBRT was G0 in 42 patients (56.8%), G1 in 22 (29.7%), G2 in 9 (12.1%), G3 in 1 (1.4%). The 3-year actuarial rates of ≥ G2 late toxicities were 6.1% for genito-urinary and 8.9% for gastrointestinal. The whole image-guidance workflow resulted in being robust and reliable. EBRT delivered employing a hypofractionated schedule under 3D-US-based image guidance proved to be a safe and effective treatment approach with consistent biochemical control and a mild toxicity profile. Hence, it has been transferred into daily clinical practice in our Department.

Volumetric and positional changes of planning target volumes and organs at risk using computed tomography imaging during intensity-modulated radiation therapy for head-neck cancer: an "old" adaptive radiation therapy approach.

PURPOSE: This study aimed to assess, in a department of radiation oncology not equipped with in-room imaging systems, volumetric and positional changes of planning target volumes (PTVs) and organs at risk in head and neck (H&N) cancer patients treated with intensity-modulated radiation therapy (IMRT), using consecutive off-board computed tomography (CT) imaging. Dosimetric aspects were not investigated. MATERIALS AND METHODS: Ten patients with H&N cancer underwent CT re-scanning at 3, 5, and 7 weeks. Positional changes of the PTVs and parotid glands as distances relative to the virtual isocentre were determined. The parotids glands (PGs) were re-delineated on each CT set and volume differences were computed. Anterior-posterior (AP) and latero-lateral (LL) displacements for the spinal cord at C1 and C6 level were calculated. Changes in patient body contours were evaluated by comparing the volumes within the external skin outline. RESULTS: Apart from two patients requiring re-planning due to substantial weight loss, our results evidenced no significant shifts of PTVs and PGs. PG volume decreased with a trend in volume reduction for the ipsilateral parotid. No significant shift of spinal cord at C1 and C6 level was detected, in either the AP or LL direction. The collected data demonstrated a trend in external skin contour volume loss. CONCLUSIONS: Our preliminary results reflect the literature data and indicate that an off-line adaptive RT approach is appropriate in clinical practice.