Modelling Radiation-Induced Salivary Dysfunction during IMRT and Chemotherapy for Nasopharyngeal Cancer Patients.

BACKGROUND: Radiation-induced xerostomia is one of the most prevalent adverse effects of head and neck cancer treatment, and it could seriously affect patients' qualities of life. It results primarily from damage to the salivary glands, but its onset and severity may also be influenced by other patient-, tumour-, and treatment-related factors. We aimed to build and validate a predictive model for acute salivary dysfunction (aSD) for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors. METHODS: A cohort of consecutive NPC patients treated curatively with IMRT and chemotherapy at 70 Gy (2-2.12 Gy/fraction) were utilised. Parotid glands (cPG, considered as a single organ) and the oral cavity (OC) were selected as organs-at-risk. The aSD was assessed at baseline and weekly during RT, grade ≥ 2 aSD chosen as the endpoint. Dose-volume histograms were reduced to the Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Model validation was performed on two cohorts of patients with prospective aSD, and scored using the same schedule/scale: a cohort (NPC_V) of NPC patients (as in model training), and a cohort of mixed non-NPC head and neck cancer patients (HNC_V). RESULTS: The model training cohort included 132 patients. Grade ≥ 2 aSD was reported in 90 patients (68.2%). Analyses resulted in a 4-variables model, including doses of up to 98% of cPG (cPG_D98%, OR = 1.04), EUD to OC with n = 0.05 (OR = 1.11), age (OR = 1.08, 5-year interval) and smoking history (OR = 1.37, yes vs. no). Calibration was good. The NPC_V cohort included 38 patients, with aSD scored in 34 patients (89.5%); the HNC_V cohort included 93 patients, 77 with aSD (92.8%). As a general observation, the incidence of aSD was significantly different in the training and validation populations (p = 0.01), thus impairing calibration-in-the-large. At the same time, the effect size for the two dosimetric factors was confirmed. Discrimination was also satisfactory in both cohorts: AUC was 0.73, and 0.68 in NPC_V and HNC_V cohorts, respectively. CONCLUSION: cPG D98% and the high doses received by small OC volumes were found to have the most impact on grade ≥ 2 acute xerostomia, with age and smoking history acting as a dose-modifying factor. Findings on the development population were confirmed in two prospectively collected validation populations.

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.

BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.

Back to (new) normality-A CODRAL/AIRO-L survey on cancer radiotherapy in Lombardy during Italian COVID-19 phase 2.

BACKGROUND: Italy experienced one of the world's severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery. MATERIALS AND METHODS: A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after. RESULTS: All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients. CONCLUSION: The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments.

Methodology and technology for the development of a prognostic MRI-based radiomic model for the outcome of head and neck cancer patients.

The purpose of this study was to establish a methodology and technology for the development of an MRI-based radiomic signature for prognosis of overall survival (OS) in nasopharyngeal cancer from non-endemic areas. The signature was trained using 1072 features extracted from the main tumor in T1-weighted and T2-weighted images of 142 patients. A model with 2 radiomic features was obtained (RAD model). Tumor volume and a signature obtained by training the model on permuted survival data (RADperm model) were used as a reference. A 10-fold cross-validation was used to validate the signature. Harrel's C-index was used as performance metric. A statistical comparison of the RAD, RADperm and volume was performed using Wilcoxon signed rank tests. The C-index for the RAD model was higher compared to the one of the RADperm model (0.69±0.08 vs 0.47±0.05), which ensures absence of overfitting. Also, the signature obtained with the RAD model had an improved C-index compared to tumor volume alone (0.69±0.08 vs 0.65±0.06), suggesting that the radiomic signature provides additional prognostic information.

A monocentric, open-label randomized standard-of-care controlled study of XONRID®, a medical device for the prevention and treatment of radiation-induced dermatitis in breast and head and neck cancer patients.

BACKGROUND: This study was an open-label, 2-arms, monocentric, randomized clinical trial comparing Xonrid®, a topical medical device, versus standard of care (SOC) in preventing and treating acute radiation dermatitis (ARD) in Head and Neck Cancer (HNC) and Breast Cancer (BC) patients undergoing radiotherapy (RT). METHODS: Eligible HNC and BC patients were randomized 1:1 to receive Xonrid® + SOC or SOC during RT. Patients were instructed to apply Xonrid® on the irradiated area three times daily, starting on the first day of RT and until 2 weeks after RT completion or until the development of grade ≥ 3 skin toxicity. The primary endpoint was to evaluate the proportion of patients who developed an ARD grade < 2 at the 5th week in both groups. Secondary endpoints were median time to grade 2 (G2) skin toxicity onset; changes in skin erythema and pigmentation and trans-epidermal water loss (TEWL); patient-reported skin symptoms. All patients were evaluated at baseline, weekly during RT and 2 weeks after treatment completion. The evaluation included: clinical toxicity assessment; reflectance spectrometry (RS) and TEWL examination; measurement of patients' quality of life (QoL) through Skindex-16 questionnaire. RESULTS: Eighty patients (40 for each cancer site) were enrolled between June 2017 and July 2018. Groups were well balanced for population characteristics. All BC patients underwent 3-Dimensional Conformal RT (3D-CRT) whereas HNC patients underwent Volumetric-Modulated Arc Therapy (VMAT). At week 5 the proportion of BC patients who did not exhibit G2 ARD was higher in Xonrid® + SOC group (p = 0.091). In the same group the onset time of G2 ARD was significantly longer than in SOC-alone group (p < 0.0491). For HNC groups there was a similar trend, but it did not reach statistical significance. For both cancer sites, patients' QoL, measured by the Skindex-16 score, was always lower in the Xonrid® + SOC group. CONCLUSION: Despite the failure to achieve the primary endpoint, this study suggests that Xonrid® may represent a valid medical device in the prevention and treatment of ARD at least in BC patients, delaying time to develop skin toxicity and reducing the proportion of patients who experienced G2 ARD during RT treatment and 2 weeks later. TRIAL REGISTRATION: The study was approved by the Ethical Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT 52/14 - NCT02261181 ). Registered on ClinicalTrial.gov on 21st August 2017.

Prognostic role of primary tumor, nodal neck, and retropharyngeal GTVs for unresectable sinonasal cancers treated with IMRT and chemotherapy.

BACKGROUND: We evaluated the prognostic role of gross tumor volumes (GTVs) of primary tumor and positive lymph nodes on overall survival (OS) and progression-free survival (PFS) in locally advanced unresectable sinonasal cancer (SNC) treated with definitive intensity-modulated radiotherapy (IMRT) with or without chemotherapy. METHODS: Primary tumor GTV (GTV-T), pathologic neck nodes GTV (GTV-N), and positive retropharyngeal nodes GTV (GTV-RPN) of 34 patients with epithelial nonglandular SNC receiving IMRT with or without chemotherapy were retrospectively measured. The GTV variables were analyzed in relation with OS and PFS. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. We also estimated the crude cumulative incidence of locoregional relapses only. The optimal volume cutoff value was determined using an outcome-oriented method among the observed values. RESULTS: GTV-T was significantly associated with decreased OS (P=0.003) and PFS (P=0.003). Moreover, patients with disease total volumes (GTV) smaller than 149.44 cm³ had better OS and PFS than patients with higher volumes (P<0.0001 for both). Neck nodal metastasis impacted on OS and PFS (P=0.030 and P=0.033, respectively), but GTV-N did not (P=0.961; P=0.958). Retropharyngeal nodes metastasis was not associated with prognosis (OS: P=0.400; PFS: P=0.104). When GTV-RPN was added to GTV-N (GTV-TN), a relation with PFS (P=0.041) and a trend toward significance for OS (P=0.075) were found. CONCLUSIONS: Our results show that tumor volume is a powerful predictor of outcome in SNC. This could be useful to identify patients with worse prognosis deserving different treatment strategies.

Postoperative radiotherapy (PORT) for early oral cavity cancer (pT1-2,N0-1): A review.

Early stage (T1-2, N0-1) oral squamous cell carcinoma (OSCC) has a generally favorable prognostic outcome. However, locoregional recurrences can occur in up to 30-35% of patients, and 20% will eventually die of disease. National and international treatment guidelines do not recommend the use of postoperative radiotherapy (PORT) in a setting of early OSCC, and highlight surgery alone as the standard single modality treatment. Notwithstanding, the negative prognostic impact of some adverse pathological features, such as perineural and lymphovascular invasion, poor differentiation, depth of invasion >4 mm, and presence of nodal metastasis, is well known. The advantages of PORT in such scenarios are still debated. The aim of this study was to review the more recent literature to provide evidence on the benefits of PORT in the context of early stage OSCC.

Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group.

BACKGROUND: To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. METHODS: We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population. RESULTS: Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm3 were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability. CONCLUSION: Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population.

High-dose-rate brachytherapy for high-grade vaginal intraepithelial neoplasia: a dosimetric analysis.

PURPOSE: Due to the rarity of vaginal intraepithelial neoplasia (VAIN), it is impossible to define the best treatment approach or to assess vaginal morbidity. However, brachytherapy (BT) could be a valuable choice for VAIN grade 3 (VAIN3). The aim of this paper was to report a single-institution study of the application of high-dose-rate BT and to evaluate clinical outcomes as well as to investigate the dose-effect relationship for vaginal stenosis. MATERIAL AND METHODS: We retrospectively collected hospital records and treatment plans of 14 consecutive women treated in our department from August 2010 to August 2016, with HDR-BT delivered using iridium-192 by a remote after-loading system. Doses in 3D-planned treatment based on computed tomography (CT) were prescribed in high-risk clinical target volume (HR-CTV) at the vaginal wall. Vaginal stenosis was defined as vaginal shortening/narrowing according to CTCAE4.1. The International Commission on Radiation Units & Measurements (ICRU) bladder and rectal points were used for dose report analysis. The posterior-inferior border of the symphysis points was used to derive reference points. The median age of the enrolled women was 60 years, and the median total radiation dose delivered was 35 Gy. RESULTS: During a median period of 15 days, the treatment was well tolerated, and no interruption was necessary. Acute toxicity was minimal, whereas late toxicity appeared in 4 patients as G2 and in 3 patients as G3 vaginal stenosis. Patients with stenosis G ≥ 2 received a higher median dose to the rectal point and were mainly over 60 years old. CONCLUSIONS: Patients with VAIN3 seemed to benefit from BT. It is generally assumed that the vagina is radio-resistant, and no constraints have yet been set, but sexual dysfunction after BT is an important cause of long-term distress. Finding applicable dose limits to the vagina could improve patients' quality of life.

Combination of Immunotherapy and Brain Radiotherapy in Metastatic Melanoma: A Retrospective Analysis.

BACKGROUND: Up to 40% of patients with metastatic melanoma (MM) develop brain metastases. Radiotherapy (RT) may potentiate the effects of immunotherapy (IO), even on distant sites (abscopal effect). MATERIAL AND METHODS: We retrospectively analyzed all our MM patients treated with IO within 6 months before/after brain RT between 2012 and 2016. Progression-free (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with those of controls treated with IO during the same period. RESULTS: Thirty-six cases and 25 controls were identified. Among cases, 23 patients received an anti-CTLA4 agent and 13 an anti-PD1 agent. Eighteen cases were treated with stereotactic RT and 18 with whole-brain RT. Median PFS from the beginning of RT was 4 months in first-line and 2 months in second-line treatment. A third of the cases progressed at first evaluation after RT. Median OS from the beginning of RT was 7 months in first-line and 4 months in second-line treatment. Median PFS and OS of each treatment line showed a trend towards inferiority compared with those of controls. CONCLUSION: Synergism between RT and IO was not observed in our case series. No cases of abscopal effect were seen, and most patients underwent early systemic progression after RT.

A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes.

Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8+ effector memory cells, in SNUC) and "other cells": keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic ß-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities.

Predictors of Patient-Reported Dysphagia Following IMRT Plus Chemotherapy in Oropharyngeal Cancer.

The aim of this cross-sectional study is to evaluate the factors associated with patient-reported dysphagia in patients affected by locally advanced oropharyngeal cancer (OPC) treated with definitive intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CHT), with or without induction CHT. We evaluated 148 OPC patients treated with IMRT and concurrent CHT, without evidence of disease and who had completed their treatment since at least 6 months. At their planned follow-up visit, patients underwent clinical evaluation and completed the M.D. Anderson dysphagia inventory (MDADI) questionnaire. The association between questionnaire composite score (MDADI-CS) and different patients' and tumor's characteristics and treatments (covariates) was investigated by univariable and multivariable analyses, the latter including only covariates significant at univariable analysis. With a median time from treatment end of 30 months [range 6-74 months, interquartile range (IQR) 16-50 months], the median (IQR) MDADI-CS was 72 (63-84). The majority of patients (82.4%) had a MDADI-CS ≥ 60. At multivariable analysis, female gender, human papilloma virus (HPV)-negative status, and moderate and severe clinician-rated xerostomia were significantly associated with lower MDADI-CS. Patient-perceived dysphagia was satisfactory or acceptable in the majority of patients. HPV status and xerostomia were confirmed as important predictive factors for swallowing dysfunction after radiochemotherapy. Data regarding female gender are new and deserve further investigation.

Role of pretreatment 18F-FDG PET/CT parameters in predicting outcome of non-endemic EBV DNA-related nasopharyngeal cancer (NPC) patients treated with IMRT and chemotherapy.

PURPOSE: To evaluate the prognostic role of pretreatment 18F-FDG PET/CT metabolic parameters in non-endemic Epstein-Barr Virus (EBV DNA)-related nasopharyngeal cancer (NPC) patients treated with curative intensity-modulated radiation therapy (IMRT) with or without chemotherapy (CHT). MATERIALS/METHODS: We retrospectively reviewed clinical data of 160 consecutive non-metastatic NPC patients who received IMRT with or without CHT. Forty-nine out of 160 patients that underwent whole body 18F-FDG PET/CT at our institution for disease staging with a minimum follow-up to 12 months were included in this study. We evaluated the relationship between maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume and total lesion glycolysis (TLG) of primary tumor and cervical lymph nodes with disease-free survival (DFS) and overall survival (OS). We also investigated the prognostic role of clinical variables such as age, disease stage, plasma EBV DNA load (copies/ml), gross tumor volume of primary tumor and lymph nodes. RESULTS: Median follow-up was 55 months. Two- and 5-year OS were 95.8% and 90.5%, respectively, while DFS was 83.4% at both time points. SUVmax of primary tumor ≥ 18.8 g/ml and primary tumor TLG ≥ 203.1 g were significant prognostic factors of worse OS. Furthermore, stages IVB and EBV DNA load ≥ 3493 copies/ml were significantly associated with lower DFS. No correlation was found between PET parameters and plasma EBV DNA load. CONCLUSION: Even in a limited series, our data suggested that SUVmax, SUVmean and TLG of primary tumor could predict a poor outcome in NPC patients also in non-endemic area hypothesizing their use for refinement of prognostication.

Impact of treatment expertise on the outcome of patients with head and neck cancer treated within 6 randomized trials.

BACKGROUND: We evaluated the impact of center expertise, in terms of number of patients treated, on the overall survival (OS) and progression-free survival (PFS) of patients with head and neck squamous cell carcinoma (SCC). METHODS: We performed a pooled analysis including data from 6 randomized trials in head and neck SCC conducted in Italy. We evaluated the association between OS or PFS and the number of patients recruited by the center. RESULTS: The outcome of 903 patients who had received radiotherapy (RT) was analyzed (median follow-up 76 months). The hazard ratio (HR) comparing the third and the first quartiles of the distribution of number of patients per center showed an advantage in PFS (HR 0.59, range 0.53-0.65, P < .0001) and in OS (HR 0.70, 0.60-0.81, P < .0001) for centers with a higher number of patients recruited. A similar benefit was observed in PFS (HR 0.63, 0.60-0.66) and OS (HR 0.74, 0.69-0.79) considering the mean number of patients per year. CONCLUSIONS: The PFS and OS were longer for patients treated in high-case-volume centers.

Multivariable model for predicting acute oral mucositis during combined IMRT and chemotherapy for locally advanced nasopharyngeal cancer patients.

INTRODUCTION/OBJECTIVE: Oral and oropharyngeal mucositis (OM) represents amultifactorialand complexinterplayof patient-, tumor-, and treatment-related factors. We aimed to build a predictive model for acute OM for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors. MATERIALS/METHODS: A series of consecutive NPC patients treated curatively with IMRT/VMAT + chemotherapy at 70 Gy (2-2.12 Gy/fr) was considered. For each patient, clinical- tumor- and treatment-related data were retrospectively collected. oral cavity (OC) and parotid glands (PG, considered as a single organ) were selected as organs-at-risk (OARs). Acute OM was assessed according to CTCAE v4.0 at baseline and weekly during RT. Two endpoints were considered: grade ≥3 and mean grade ≥1.5. DVHs were reduced to Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Goodness of fit was evaluated through Hosmer-Lemeshow test and calibration plot. RESULTS: Data were collected for 132 patients. G ≥ 3 and mean G ≥ 1.5 OM were reported in 40 patients (30%). Analyses resulted in a 3-variables model for G ≥ 3 OM, including OC EUD with n = 0.05 (OR = 1.02), PG EUD with n = 1 (OR = 1.06), BMI ≥ 30 (OR = 3.8, for obese patients), and a single variable model for mean G ≥ 1.5 OM, i.e. OC EUD with n = 1 (mean dose) (OR = 1.07). Calibration was good in both cases. CONCLUSION: OC mean dose was found to impact most on OM duration (mean G ≥ 1.5), while G ≥ 3 OM was associated to a synergic effect between PG mean dose and high dose received by small OC volumes, with BMI acting as a dose-modifying factor.

Pre-implant magnetic resonance and transrectal ultrasound imaging in high-dose-rate prostate brachytherapy: comparison of prostate volumes, craniocaudal extents, and contours.

PURPOSE: The purpose of this study was to compare the prostate contours drawn by two radiation oncologists and one radiologist on magnetic resonance (MR) and transrectal ultrasound (TRUS) images. TRUS intra- and inter-fraction variability as well as TRUS vs. MR inter-modality and inter-operator variability were studied. MATERIAL AND METHODS: Thirty patients affected by localized prostate cancer and treated with interstitial high-dose-rate (HDR) prostate brachytherapy at the National Cancer Institute in Milan were included in this study. Twenty-five patients received an exclusive two-fraction (14 Gy/fraction) treatment, while the other 5 received a single 14 Gy fraction as a boost after external beam radiotherapy. The prostate was contoured on TRUS images acquired before (virtual US) and after (real US) needle implant by two radiation oncologists, whereas on MR prostate was independently contoured by the same radiation oncologists (MR1, MR2) and by a dedicated radiologist (MR3). Absolute differences of prostate volumes (│ΔV│) and craniocaudal extents (│Δdz│) were evaluated. The Dice's coefficient (DC) was calculated to quantify spatial overlap between MR contours. RESULTS: Significant difference was found between Vvirtual and Vlive (p < 0.001) for the first treatment fractions and between VMR1 and VMR2 (p = 0.043). Significant difference between cranio-caudal extents was found between dzvirtual and dzlive (p < 0.033) for the first treatment fractions, between dzvirtual of the first treatment fractions and dzMR1 (p < 0.001) and between dzMR1 and dzMR3 (p < 0.01). Oedema might be responsible for some of the changes in US volumes. Average DC values resulting from the comparison MR1 vs. MR2, MR1 vs. MR3 and MR2 vs. MR3 were 0.95 ± 0.04 (range, 0.82-0.99), 0.87 ± 0.04 (range, 0.73-0.91) and 0.87 ± 0.04 (range, 0.72-0.91), respectively. CONCLUSIONS: Our results demonstrate the importance of a multiprofessional approach to TRUS-guided HDR prostate brachytherapy. Specific training in MR and US prostate imaging is recommended for centers that are unfamiliar with HDR prostate brachytherapy.

Equipment, staffing, and provision of radiotherapy in Lombardy, Italy: Results of three surveys performed between 2012 and 2016.

INTRODUCTION:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent. METHODS:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources. RESULTS:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014). CONCLUSIONS:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

Failure of Further Validation for Survival Nomograms in Oropharyngeal Cancer: Issues and Challenges.

PURPOSE: To retrospectively test 2 nomograms recently validated as prognostic tools for patients with oropharyngeal cancer treated with curative radiation-based therapy, in 184 consecutive subjects treated from April 2004 to January 2016. PATIENT AND METHODS: Complete information regarding disease, survival status, and nomogram covariates was retrieved for 174 patients, with a median follow-up of 51 months. Calibration of the nomograms was obtained by evaluating the ability to accurately predict the absolute risk level; discriminative ability estimated by the Harrell C statistic was tested by assessing the ability of the nomograms to rank the patients from low risk to high risk. RESULTS: The outcome predicted by the nomograms was worse than observed, especially for progression-free survival. This may be due to several factors: geographic and genetic background, smoking, alcohol use, the different national health system organization, which provides universal and free-of-charge coverage to all individuals, and the setting of treatment in clinical practice, outside of clinical trials. CONCLUSIONS: Our results show that the usefulness of nomograms to predict outcome of oropharyngeal cancer may not be generalizable to patients of different countries. Further studies are needed to clarify whether sociodemographic, epidemiologic, and cultural scenarios may seriously affect the prognostic ability of newly developed predictive tools.

Semiconductor real-time quality assurance dosimetry in brachytherapy.

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.