Pelvic bone marrow dose-volume predictors of late lymphopenia following pelvic lymph node radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study. MATERIALS AND METHODS: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/µL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap. RESULTS: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation. CONCLUSIONS: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.

Inter-institutional variability of knowledge-based plan prediction of left whole breast irradiation.

PURPOSE: Within a multi-institutional project, we aimed to assess the transferability of knowledge-based (KB) plan prediction models in the case of whole breast irradiation (WBI) for left-side breast irradiation with tangential fields (TF). METHODS: Eight institutions set KB models, following previously shared common criteria. Plan prediction performance was tested on 16 new patients (2 pts per centre) extracting dose-volume-histogram (DVH) prediction bands of heart, ipsilateral lung, contralateral lung and breast. The inter-institutional variability was quantified by the standard deviations (SDint) of predicted DVHs and mean-dose (Dmean). The transferability of models, for the heart and the ipsilateral lung, was evaluated by the range of geometric Principal Component (PC1) applicability of a model to test patients of the other 7 institutions. RESULTS: SDint of the DVH was 1.8 % and 1.6 % for the ipsilateral lung and the heart, respectively (20 %-80 % dose range); concerning Dmean, SDint was 0.9 Gy and 0.6 Gy for the ipsilateral lung and the heart, respectively (<0.2 Gy for contralateral organs). Mean predicted doses ranged between 4.3 and 5.9 Gy for the ipsilateral lung and 1.1-2.3 Gy for the heart. PC1 analysis suggested no relevant differences among models, except for one centre showing a systematic larger sparing of the heart, concomitant to a worse PTV coverage, due to high priority in sparing the left anterior descending coronary artery. CONCLUSIONS: Results showed high transferability among models and low inter-institutional variability of 2% for plan prediction. These findings encourage the building of benchmark models in the case of TF-WBI.

Quality of Life Longitudinal Evaluation in Prostate Cancer Patients from Radiotherapy Start to 5 Years after IMRT-IGRT.

PURPOSE: The purpose of this study is to study the evolution of quality of life (QoL) in the first 5 years following Intensity-modulated radiation therapy (IMRT) for prostate cancer (PCa) and to determine possible associations with clinical/treatment data. MATERIAL AND METHODS: Patients were enrolled in a prospective multicentre observational trial in 2010-2014 and treated with conventional (74-80 Gy, 1.8-2 Gy/fr) or moderately hypofractionated IMRT (65-75.2 Gy, 2.2-2.7 Gy/fr). QoL was evaluated by means of EORTC QLQ-C30 at baseline, at radiation therapy (RT) end, and every 6 months up to 5 years after IMRT end. Fourteen QoL dimensions were investigated separately. The longitudinal evaluation of QoL was analysed by means of Analysis of variances (ANOVA) for multiple measures. RESULTS: A total of 391 patients with complete sets of questionnaires across 5 years were available. The longitudinal analysis showed a trend toward the significant worsening of QoL at RT end for global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. QoL worsening was recovered within 6 months from RT end, with the only exception being physical functioning. Based on ANOVA, the most impaired time point was RT end. QoL dimension analysis at this time indicated that acute Grade ≥ 2 gastrointestinal (GI) toxicity significantly impacted global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. Acute Grade ≥ 2 genitourinary (GU) toxicity resulted in lower role functioning and higher pain. Prophylactic lymph-nodal irradiation (WPRT) resulted in significantly lower QoL for global health, fatigue, appetite loss, and diarrhoea; lower pain with the use of neoadjuvant/concomitant hormonal therapy; and lower fatigue with the use of an anti-androgen. CONCLUSIONS: In this prospective, longitudinal, observational study, high radiation IMRT doses delivered for PCa led to a temporary worsening of QoL, which tended to be completely resolved at six months. Such transient worsening was mostly associated with acute GI/GU toxicity, WPRT, and higher prescription doses.

Nanodiamond Effects on Cancer Cell Radiosensitivity: The Interplay between Their Chemical/Physical Characteristics and the Irradiation Energy.

Nanoparticles are being increasingly studied to enhance radiation effects. Among them, nanodiamonds (NDs) are taken into great consideration due to their low toxicity, inertness, chemical stability, and the possibility of surface functionalization. The objective of this study is to explore the influence of the chemical/physical properties of NDs on cellular radiosensitivity to combined treatments with radiation beams of different energies. DAOY, a human radioresistant medulloblastoma cell line was treated with NDs-differing for surface modifications [hydrogenated (H-NDs) and oxidized (OX-NDs)], size, and concentration-and analysed for (i) ND internalization and intracellular localization, (ii) clonogenic survival after combined treatment with different radiation beam energies and (iii) DNA damage and apoptosis, to explore the nature of ND-radiation biological interactions. Results show that chemical/physical characteristics of NDs are crucial in determining cell toxicity, with hydrogenated NDs (H-NDs) decreasing either cellular viability when administered alone, or cell survival when combined with radiation, depending on ND size and concentration, while OX-NDs do not. Also, irradiation at high energy (γ-rays at 1.25 MeV), in combination with H-NDs, is more efficient in eliciting radiosensitisation when compared to irradiation at lower energy (X-rays at 250 kVp). Finally, the molecular mechanisms of ND radiosensitisation was addressed, demonstrating that cell killing is mediated by the induction of Caspase-3-dependent apoptosis that is independent to DNA damage. Identifying the optimal combination of ND characteristics and radiation energy has the potential to offer a promising therapeutic strategy for tackling radioresistant cancers using H-NDs in conjunction with high-energy radiation.

Clinical-radiomic models based on digital breast tomosynthesis images: a preliminary investigation of a predictive tool for cancer diagnosis.

Objective: This study aimed to develop a clinical-radiomic model based on radiomic features extracted from digital breast tomosynthesis (DBT) images and clinical factors that may help to discriminate between benign and malignant breast lesions. Materials and methods: A total of 150 patients were included in this study. DBT images acquired in the setting of a screening protocol were used. Lesions were delineated by two expert radiologists. Malignity was always confirmed by histopathological data. The data were randomly divided into training and validation set with an 80:20 ratio. A total of 58 radiomic features were extracted from each lesion using the LIFEx Software. Three different key methods of feature selection were implemented in Python: (1) K best (KB), (2) sequential (S), and (3) Random Forrest (RF). A model was therefore produced for each subset of seven variables using a machine-learning algorithm, which exploits the RF classification based on the Gini index. Results: All three clinical-radiomic models show significant differences (p < 0.05) between malignant and benign tumors. The area under the curve (AUC) values of the models obtained with three different feature selection methods were 0.72 [0.64,0.80], 0.72 [0.64,0.80] and 0.74 [0.66,0.82] for KB, SFS, and RF, respectively. Conclusion: The clinical-radiomic models developed by using radiomic features from DBT images showed a good discriminating power and hence may help radiologists in breast cancer tumor diagnoses already at the first screening.

A real-time system to report abnormal events involving staff in a nuclear medicine therapy unit.

A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient's room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.

The Prognostic Value of DCE-MRI Findings before Salvage Radiotherapy after Radical Prostatectomy.

BACKGROUND: To investigate the predictive role of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) findings before salvage radiotherapy after radical prostatectomy (RP). METHODS: This retrospective study selected patients with biochemical failure (BF) after RP restaged with DCE-MRI. Patients underwent sRT in 30 fractions delivering 66-69 Gy and 73.5 Gy to the prostatic fossa and to the local failure as per DCE-MRI, respectively. Pelvic nodes were treated to 54 Gy in selected patients. The endpoint was BF after sRT. RESULTS: In total, 236 patients were analyzed and 146 (61.9%) had presumed local failure at DCE-MRI: 54.8%, 23.8% and 21.4% were found at the vesico-urethral anastomosis (VUA), the bladder neck and the retro-vesical space, respectively. The presence of a local failure at DCE-MRI halved the risk of BF; VUA-only location and lesion volume were independently correlated with survival without evidence of biochemical failure (bNED) at multivariable analysis. For patients with VUA-only disease up to 0.4 cc, the 4-year-bNED was 94.6% (95%CI: 80.2-98.6%) as opposed to 80.9% (95%CI: 71.6-87.4%) and 73.7% (95%CI: 63.1-81.8%) for other lesions and no macrodisease, respectively. CONCLUSIONS: DCE-MRI at restaging for BF after RP provides predictive and therapeutic information. Patients with small lesions at the VUA have an excellent prognosis after sRT.

Knowledge-based multi-institution plan prediction of whole breast irradiation with tangential fields.

PURPOSE: To quantify inter-institute variability of Knowledge-Based (KB) models for right breast cancer patients treated with tangential fields whole breast irradiation (WBI). MATERIALS AND METHODS: Ten institutions set KB models by using RapidPlan (Varian Inc.), following previously shared methodologies. Models were tested on 20 new patients from the same institutes, exporting DVH predictions of heart, ipsilateral lung, contralateral lung, and contralateral breast. Inter-institute variability was quantified by the inter-institute SDint of predicted DVHs/Dmean. Association between lung sparing vs PTV coverage strategy was also investigated. The transferability of models was evaluated by the overlap of each model's geometric Principal Component (PC1) when applied to the test patients of the other 9 institutes. RESULTS: The overall inter-institute variability of DVH/Dmean ipsilateral lung dose prediction, was less than 2% (20%-80% dose range) and 0.55 Gy respectively (1SD) for a 40 Gy in 15 fraction schedule; it was < 0.2 Gy for other OARs. Institute 6 showed the lowest mean dose prediction value and no overlap between PTV and ipsilateral lung. Once excluded, the predicted ipsilateral lung Dmean was correlated with median PTV D99% (R2 = 0.78). PC1 values were always within the range of applicability (90th percentile) for 7 models: for 2 models they were outside in 1/18 cases. For the model of institute 6, it failed in 7/18 cases. The impact of inter-institute variability of dose calculation was tested and found to be almost negligible. CONCLUSIONS: Results show limited inter-institute variability of plan prediction models translating in high inter-institute interchangeability, except for one of ten institutes. These results encourage future investigations in generating benchmarks for plan prediction incorporating inter-institute variability.

A prospective study assessing the pattern of response of local disease at DCE-MRI after salvage radiotherapy for prostate cancer.

Background: To assess the pattern of response of presumed local lesions at dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) after salvage radiotherapy (sRT). Methods: This is a prospective study conducted at a single Institution accruing patients with one or more local failures at DCE-MRI after radical prostatectomy between August 2017 and June 2020. Patients underwent exclusive sRT delivering 66-69 Gy and 73.5 Gy in 30 fractions to the whole prostatic fossa and to the local failure(s) seen at DCE-MRI, respectively.Patients were offered DCE-MRI at 3 months intervals after sRT until complete disappearance (CR) of the lesion(s) or up to a maximum of 4 revaluations. Results: 62 patients with 72 nodules were enrolled. All patients underwent the 1st revaluation, and 33 patients (53.2%) showed a CR. The median time to CR was 4.7 months. Four patients did not undergo further testing before achieving a CR and even considering these patients as no responses, the vast majority (87.1%, 95%CI: 78.5-94.4%) of lesions would have completely disappeared by 12 months from the end of sRT.The volume of the lesion at pre-sRT DCE-MRI was an independent predictor of CR at the 1st revaluation (OR: 0.076, 95%CI: 0.009-0.667; p = 0.020) along with time elapsed from sRT (OR: 3.399, 95% CI: 1.156-9.993, p = 0.026). Conclusions: The present study documents the complete disappearance of the vast majority of local lesions after dose-escalated sRT though this requires several months after sRT; timing of CR is at least in part predictable based on the volume of the lesion.Trial registration: Clinicaltrials.gov NCT04703543, registered July 15 2020, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04703543.

Comparison of rigid and deformable coregistration between mpMRI and CT images in radiotherapy of prostate bed cancer recurrence.

PURPOSE: To evaluate the accuracy of rigid coregistration between multiparametric magnetic resonance (mpMR) and computed tomography (CT) images for radiotherapy of prostate bed cancer recurrence. MATERIALS AND METHOD: Fifty-three patients (59 nodules) accrued in a prospective study on salvage radiotherapy for prostatic bed recurrence were suitable for the analysis. Patients underwent a pre radiotherapy mpMR exam and a planning CT in the same treatment position and with control of organ filling. The site of recurrence was delineated on mpMR images and contours transferred on planning CT images using both rigid and deformable registrations. Coregistrations were evaluated by mathematical operators that quantify deformation (Jacobian determinant and vector curl) and similarity indices (Dice and Jaccard coefficients). Dose coverage was evaluated. RESULTS: Deformable registration did not change volumes, (p = 0.92 MW test). The Jacobian coefficient and the vector curl revealed no important image deformations. Dice and Jaccard coefficients indicated dislocation of the nodule volumes. Dislocation magnitude was d = (5.6 ± 3.1) mm. Organ filling was not correlated with deformation or dislocation. Volumes were covered by the 95% isodose in 96% of cases when rigid registration was performed versus 75% of cases when deformed. CONCLUSIONS: Rigid image coregistration is sufficiently accurate in this setting. The results indicate that the deformable registration tends to shrink the voxels and to dislocate the ROI, the adopted expansion for the recurrence volume adequately accounts for the observed deformation and dislocation, provided that organ filling is controlled.

A Prospective Study Assessing the Post-Prostatectomy Detection Rate of a Presumed Local Failure at mpMR with Either 64CuCl2 or 64CuPSMA PET/CT.

BACKGROUND: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). METHODS: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP; subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater); a presumed local failure at mpMR; no distant metastases at 18F-fluorocholine PET/CT (CH/PET); no previous history of androgen deprivation therapy. Patients were offered both 64CuCl2 PET/CT (CU/PET) and 64Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. RESULTS: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9-100%), DRs were 47.2% (95%CI: 36.1-58.6%) and 54.4% (95%CI: 42.7-65.7%) for CU/PET and PSMA/PET, respectively (p < 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. CONCLUSIONS: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy.

Organ motion in linac-based SBRT for glottic cancer.

PURPOSE: The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. METHODS AND MATERIALS: Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. RESULTS: For the population systematic (Æ©) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Æ©) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). CONCLUSIONS: In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

Stereotactic body radiotherapy for T1 glottic cancer: dosimetric data in 27 consecutive patients.

AIM: Because the clinical feasibility of stereotactic body radiotherapy (SBRT) for early glottic cancer (T1) is controversial, we report dosimetric results in 27 consecutive patients from a prospective phase I and II study that started in 2017. METHODS: In our approach, only the parts of the true vocal cord containing cancer and those immediately adjacent are planned to be treated to 36 Gy and 30 Gy, respectively, in 3 fractions. Several dosimetric metrics for both target volumes and organs at risk were extracted from individual plans and results were compared to those achieved by other authors in a similar setting. RESULTS: Proper coverage was reached at planning in 2/3 of planning treatment volume 30 Gy, but only 4 planning treatment volume 36 Gy; conversely, the maximum dose objective was met for most of the patients on either arytenoid cartilage, but this was not the case for 51.9% and 96.3% of cricoid and thyroid cartilages, respectively. Our dosimetric results are similar to if not better than those achieved by others. CONCLUSION: SBRT in 3 fractions for T1 glottic lesions is dosimetrically challenging. Clinical validation is awaited.

Toxicity at 1 Year After Stereotactic Body Radiation Therapy in 3 Fractions for Localized Prostate Cancer.

PURPOSE: To assess the toxicity profile of prostate cancer stereotactic body radiation therapy (SBRT) in 3 fractions. METHODS AND MATERIALS: This was a prospective, multicenter phase 2 toxicity study enrolling patients with low to favorable intermediate-risk prostate cancer. Before simulation, 3 to 4 fiducial markers along with a rectal spacer were placed. The target (prostate only) was prescribed 40 Gy, whereas the maximum dose to the urethra was limited to 33 Gy with the highest priority at planning; less stringent objectives were placed on the bladder, the filling of which was controlled via a Foley catheter. Treatment was delivered every other day. Toxicity was prospectively scored with Common Terminology Criteria for Adverse Events, and several patient-reported outcomes were collected. The maximum allowed prevalence rate of grade 2+ genitourinary (GU) toxicity at 1 year was set at 15%, and the study was sized accordingly. RESULTS: Between November 2015 and May 2019, 59 patients were enrolled by 3 participating institutions. Acute gastrointestinal toxicity was occasional and mild, whereas 11.9% of patients developed acute grade 2 GU toxicity and 1.7% developed acute grade 3 GU toxicity. No patient had persistent treatment-related grade 2+ GU toxicity at 12 months after SBRT; thus, the null hypothesis was rejected. We observed a clinically relevant worsening of both International Prostate Symptom Score (IPSS) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores at 12 months compared with baseline. Moreover, we found a strong association between all selected bladder dose/volume metrics at planning and ICIQ-SF worsening at 12 months, whereas for the IPSS, the correlation with bladder dose metrics was marginal. CONCLUSIONS: The results suggest that at 12 months after treatment, the toxicity profile of SBRT in 3 fractions is acceptable.

Acute patient-reported intestinal toxicity in whole pelvis IMRT for prostate cancer: Bowel dose-volume effect quantification in a multicentric cohort study.

BACKGROUND AND PURPOSE: To assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. MATERIALS AND METHODS: Complete data of 415 patients enrolled in a multi institute, prospective trial (#NCT02803086) treated with radical (31%), adjuvant (33%) and salvage (36%) intent at a median dose to pelvic nodes/lymph-nodal area of 53 Gy were available. The most severe changes between baseline and radiotherapy mid-point/end toxicity assessed by Inflammatory Bowel Disease Questionnaire (only Bowel Domain) were considered (ΔIBDQ). The 25th percentile values of these score variations were set as endpoints. DVHs of bowel loops for patients with/without toxicity were compared for each endpoint, having excluded patients with baseline scores <5 (rate ranging between 2% and 7% according to the endpoint): the resulting best dosimetric predictors were combined with selected clinical parameters through multivariate logistic regression (MVA) to derive predictive models. RESULTS: ΔIBDQ ranged between 0.2-1.5 points considering separately each IBDQ symptom. Only four symptoms (IBDQ1 = frequency, IBDQ5 = diarrhea, IBDQ17 = gas passage, IBDQ24 = urgency) showed a median worsening ≥ 1; DVH predicted the risk of worse symptoms for IBDQ5, IBDQ24 and overall Bowel Domain. At multivariable analysis DVHs (best cut-off: V46Gy ≥80 cc) and baseline scores (Odd-Ratio:0.35-0.65) were independently associated to the three end-points. The resulting models were reliable (H&L test: 0.453-0.956), well calibrated (calibration plot: slope = 0.922-1.069, R2 = 0.725-0.875) and moderately discriminative (Area Under the Curve:0.628-0.669). A bootstrap-based validation confirmed their robustness. CONCLUSION: Constraining the bowel loops (V46 < 80 cc) may reduce the risk of several moderate intestinal symptoms, with a much greater impact for patients with lower IBDQ baseline scores.

Response on DCE-MRI predicts outcome of salvage radiotherapy for local recurrence after radical prostatectomy.

OBJECTIVE: To assess the predictive role of response on dynamic contrast enhancement on magnetic resonance imaging (DCE-MRI) of visible local lesions in the setting of salvage radiotherapy (sRT) after radical prostatectomy. METHODS: All patients referred for sRT for biochemical failure after radical prostatectomy from February 2014 to September 2016 were considered eligible if they had been restaged with DCE-MRI and had been found to have a visible lesion in the prostatic bed, but no distant/nodal disease on choline positron emission tomography (PET)-computed tomography (CT). Eligible patients were contacted during follow-up and offered reimaging with serial DCE-MRI until lesion resolution. Complete response (CR) was defined as the disappearance of the target lesion on DCE-MRI; prostate-specific antigen (PSA) recurrence was defined as a 0.2 ng/mL PSA rise above the nadir. Median follow-up after sRT was 41.5 months (range, 12.1-61.2 months). RESULTS: Fifty-nine patients agreed to undergo repeated DCE-MRI for a total of 64 studied lesions. Overall, 57 lesions (89.1%) showed a CR after 1 (51 patients) or 2 (6 patients) scans, while 7 lesions did not show any change (no response [NR]). At 42 months, no evidence of biochemical disease (bNED) survival was 74.7±6.4% and 64.3±21.0% for patients with CR and NR lesions, respectively (hazard ratio [HR], 3.181; 95% confidence interval [CI], 0.157-64.364; p = 0.451). When only patients treated with sRT without androgen deprivation were selected (n = 41), bNED survival rates at 42 months were 72.1±8.0% and 0, respectively (HR, 52.830; 95% CI, 1.893-1474.110; p = 0.020). CONCLUSIONS: Patients whose lesions disappear during follow-up have a better outcome than those with unchanged lesions after sRT alone.

Refinement & validation of rectal wall dose volume objectives for prostate hypofractionation in 20 fractions.

BACKGROUND AND PURPOSE: Dose-volume objectives for the rectum have been proposed to limit long term toxicity after moderately hypofractionated radiotherapy (MHRT) for localized prostate cancer. The purpose of the present study is to validate and possibly refine dose volume objective for the rectal wall after 20-fraction MHRT. MATERIALS AND METHODS: All patients treated by 20-fraction MHRT at a single Institution were identified and relative rectal wall (%RW) DVH retrieved. The endpoint of the study is the development of grade 2+ late rectal bleeding (LRB) according to a modified RTOG scale. Clinical and dosimetric predictors of LRB were investigated at both uni- and multi-variable analysis. RESULTS: 293 patients were identified and analyzed. Of them, 35 (12%) developed the endpoint. At univariable analysis, antithrombotic drug usage (yes vs no), technique (3DCRT vs IMRT/VMAT) and several %RW DVH cut-points were significantly correlated with LRB. However, within patients treated by 3DCRT (N = 106), a bi-variable model including anti-thrombotic drug usage and selected %RW dose/volume metrics failed to identify independent dosimetric predictors of LRB. Conversely, within patients treated with intensity modulation (N = 187), the same model showed a progressively higher impact of the percent of RW receiving doses above 40 Gy. Based on this model, we were able to confirm (V32), refine (V60) and identify a novel (V50) cut-point for the %RW. CONCLUSION: We recommend the following dose volume objectives for the %RW in order to minimize the risk of LRB after 20-fraction MHRT: V32 ≤ 50%; V50 ≤ 25.8% and V60 ≤ 10%.

IMRT and brachytherapy comparison in gynaecological cancer treatment: thinking over dosimetry and radiobiology.

BACKGROUND: The role of radiotherapy and brachytherapy in the management of locally advanced cervical and endometrial cancer is well established. However, in some cases, intracavitary brachytherapy (ICBRT) is not recommended or cannot be carried out. We aimed to investigate whether external-beam irradiation delivered by means of intensity-modulated radiation therapy (IMRT) might replace ICBRT in gynaecological cancer when the standard ICBRT boost delivering cannot be administered for technical or clinical reasons. MATERIALS AND METHODS: Fifteen already delivered treatments for gynaecological cancer patients were analysed. The treatments were performed through 3-dimensional conformal radiotherapy (3D-CRT) to the whole-pelvis up to the dose of 45-50.4 Gy followed by a boost dose administered with ICBRT in high-dose-rate or pulsed-dose-rate modality. For each patient, IMRT plans were elaborated to mimic the ICBRT. We analysed the ICBRT boost versus IMRT boost in terms of dosimetric and radiobiological aspects. RESULTS: Mean conformity index value calculated on boost volume was 0.73 for ICBRT and 0.97 for IMRT. Mean conformation number was 0.24 for ICBRT boost and 0.78 for IMRT boost. Mean normal tissue complication probability (NTCP) values for 3D-CRT plus ICBRT and for IMRT (pelvis plus boost) were, respectively, 28% and 5% for rectum; 1.5% and 0.1% for urinary bladder and 8.9% and 6.1% for bowel. CONCLUSIONS: Our findings suggest that IMRT may represent a viable alternative in delivering the boost in patients diagnosed with gynaecological cancer not amenable to ICBRT.

Short course hypofractionated whole breast irradiation after conservative surgery: a single institution phase II study.

BACKGROUND: To assess the oncologic outcomes of hypofractionated whole breast irradiation (Hypo-WBI). METHODS: Eligible patients had undergone breast conservative surgery for early breast cancer (pTis-2) and none/limited nodal involvement. Hypo-WBI consisted of 34 Gy in 10 daily fractions over 2 weeks to the whole breast three-dimensional conformal radiotherapy (3DCRT), followed by a single fraction of 8 Gy to the tumor bed after 1 week (electrons). Primary endpoint is freedom from ipsilateral breast tumor recurrence (IBTR). Minimum follow up for living & event-free patients is 3 yrs.; median follow up time of the whole analyzed patient population is 5.4 yrs. (range: 1.8-11.4 yrs). RESULTS: Two hundred fifty-one patients were accrued from 2004 to 2013. All patients underwent local excision of the primary tumor to negative margins. Four patients failed in the ipsilateral breast after a median time of 3.2 years (range: 1.7-5.7 yrs) for a 5-year IBTR-free survival of 98.7% (95%CI: 97.3%-100%). IBTR-free survival was significantly higher for patients with invasive cancer than for patients with intraductal carcinoma (p = 0.036). Within patients with invasive tumors, no clear trends or associations were detected between IBTR and age, grading, molecular subtype, pT or pN stage. At 5 years, the actuarial rates of GR2 fibrosis and GR2+ teleangectasia are 2.4% (95%CI: 0-6.5%) and 7.1% (95%CI: 0.4-13.7%), respectively. Cosmesis was scored as excellent/good by ≈95% of patients and ≈60% of clinicians. CONCLUSIONS: Hypo-WBI in 3 weeks allows excellent oncologic outcomes for invasive breast cancer after conservative surgery. Patients with intraductal carcinoma should be treated with Hypo-WBI only within a controlled study. TRIAL REGISTRATION: IRE-IFO Ethical and Scientific Committee (cod. RS61/04).

Patient-reported intestinal toxicity from whole pelvis intensity-modulated radiotherapy: First quantification of bowel dose-volume effects.

BACKGROUND AND PURPOSE: Intestinal toxicity is commonly experienced during whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. The aim of the current study was to assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with WPRT for prostate cancer. MATERIALS AND METHODS: Complete data of 206 patients were available; the median dose to pelvic nodes was 51.8Gy (range 50.4-54.4, 1.7-2Gy/fr). Intestinal symptoms were assessed as changes in the Inflammatory Bowel Disease Questionnaire scores relative to the Bowel Domain (IBDQ-B) between baseline and radiotherapy mid-point/end. The 25th percentiles of the most severe worsening from baseline (ΔIBDQ-B) were set as end-points. The impact of bowel loops and sigmoid colon dose-volume/surface parameters as well as selected clinical parameters were investigated using multivariate logistic regression. RESULTS: Analyses were focused on the four questions showing a median ΔIBDQ-B>0. No dose volume/surface parameters were predictive, other than ΔIBDQ5≥3 (loose stools): when grouping patients according to bowel DVHs (high risk: V20>470cc, V30>245cc, V42>110cc; low risk: all the remaining patients), a two-variable model including high-risk DVH-shape (OR: 9.3) and age (protective, OR: 0.94) was assessed. The model showed good calibration (slope: 1.003, R2=0.92) and was found to be robust after bootstrap-based internal validation. CONCLUSIONS: Constraining the bowel loops may reduce the risk of loose stools. The risk is higher for younger patients.