Patient-reported persistent symptoms after radiotherapy and association with quality of life for prostate cancer survivors.

PURPOSE: To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). MATERIALS AND METHODS: Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010-2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined 'persistent' if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0-100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. RESULTS: The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. CONCLUSIONS: The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.

Predictive and prognostic value of inflammatory markers in locally advanced rectal cancer (PILLAR) - A multicentric analysis by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Study Group.

Background: Patients (pts) affected with locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers able to predict oncological outcomes could help in the development of risk-adapted treatment strategies. It has been suggested that inflammation parameters may have a role in predicting tumor response to nCRT and survival outcomes and in rectal cancer, but no definitive conclusion can be drawn at present. The aim of the current study is to evaluate the role of baseline inflammatory markers as prognostic and predictive factors in a large multicentric Italian cohort of LARC pts. Methods: Patients diagnosed with LARC from January 2002 to December 2019 in 9 Italian centers were retrospectively collected. Patients underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin followed by surgery. Inflammatory markers were retrieved based on a pre-treatment blood sample including HEI (hemo-eosinophils inflammation index), SII (systemic index of inflammation), NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and MLR (monocyte-to-lymphocyte ratio). Outcomes of interest were pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). Results: 808 pts were analyzed. pCR rate was 22 %, 5yOS and 5yDFS were 84.0% and 63.1% respectively. Multivariate analysis identified that a NLR cut-off value >1.2 and SII cut-off value >500 could predict pCR (p = 0.05 and 0.009 respectively). In addition to age, extramesorectal nodes and RT dose, MLR >0.18 (p = 0.03) and HEI = 3 (p = 0.05) were independent prognostic factors for DFS. Finally, age, RT dose, MLR with a cut-off >0.35 (p = 0.028) and HEI = 3 (p = 0.045) were independent predictors of OS. Conclusions: Higher values of baseline composite inflammatory markers can serve as predictors of lower pCR rates and worse survival outcomes in LARC patients undergoing nCRT. More reliable data from prospective studies could lead to the integration of these inexpensive and easy-to-derive tools into clinical practice.

Preliminary evaluation of a novel secondary check tool for intensity modulated radiotherapy treatment planning.

PURPOSE: To evaluate the dosimetric accuracy of the Delta4 Insight (DI) secondary-check dosimetry system. METHODS: Absolute dosimetry in reference conditions, output factors, percent depth doses normalized and off-axis dose profiles for different field sizes calculated by DI were compared with measurements. Dose calculations for 20 clinical IMRT/VMAT plans generated in the TPS using both AAA or AcurosXB algorithms were compared with measurements. The average difference between calculated and measured point dose in high-dose region was calculated for all cases. 3D dose measurements were performed in Delta4 Phantom+ and a comparison between calculated and measured dose distributions was performed by means of the gamma analysis with 3 %/2 mm criteria. The dose distributions calculated by DI for 20 IMRT/VMAT plans were compared with those calculated by the TPS. RESULTS: The absolute dosimetry computed by DI showed dose value in agreement with the measured one within 0.3 %. The average differences between measured and calculated output factors were less than 2.5 %. The average PDD differences were less than 0.6 %. An excellent agreement between calculations and off-axis measurements is found. The point doses calculated for the 20 recalculated plan showed good agreement with measurements with average differences less than 0.5 %. The average gamma pass rate values for the Delta4 Phantom + 3D dose analysis was greater than 97.%. The comparison of DI with theTPS showed good agreement for the used metrics. CONCLUSIONS: Delta4 Insight may provide a useful independent secondary dose verification system for IMRT/VMAT plans, complementing the traditional global QA protocols.

Implementation of a Commercial Deep Learning-Based Auto Segmentation Software in Radiotherapy: Evaluation of Effectiveness and Impact on Workflow.

Proper delineation of both target volumes and organs at risk is a crucial step in the radiation therapy workflow. This process is normally carried out manually by medical doctors, hence demanding timewise. To improve efficiency, auto-contouring methods have been proposed. We assessed a specific commercial software to investigate its impact on the radiotherapy workflow on four specific disease sites: head and neck, prostate, breast, and rectum. For the present study, we used a commercial deep learning-based auto-segmentation software, namely Limbus Contour (LC), Version 1.5.0 (Limbus AI Inc., Regina, SK, Canada). The software uses deep convolutional neural network models based on a U-net architecture, specific for each structure. Manual and automatic segmentation were compared on disease-specific organs at risk. Contouring time, geometrical performance (volume variation, Dice Similarity Coefficient-DSC, and center of mass shift), and dosimetric impact (DVH differences) were evaluated. With respect to time savings, the maximum advantage was seen in the setting of head and neck cancer with a 65%-time reduction. The average DSC was 0.72. The best agreement was found for lungs. Good results were highlighted for bladder, heart, and femoral heads. The most relevant dosimetric difference was in the rectal cancer case, where the mean volume covered by the 45 Gy isodose was 10.4 cm3 for manual contouring and 289.4 cm3 for automatic segmentation. Automatic contouring was able to significantly reduce the time required in the procedure, simplifying the workflow, and reducing interobserver variability. Its implementation was able to improve the radiation therapy workflow in our department.

Hypofractionation and Concomitant Boost in Ductal Carcinoma In Situ (DCIS): Analysis of a Prospective Case Series with Long-Term Follow-Up.

We previously reported on a cohort of breast cancer patients affected with ductal carcinoma in situ (DCIS) that were treated with breast conservative surgery and hypofractionated whole-breast radiotherapy with a concomitant boost to the lumpectomy cavity. We now report on the long-term results of the oncological and toxicity outcomes, at a median follow-up of 11.2 years. We also include an analysis of the predictive factors for local recurrence (LR). Eighty-two patients with long-term observation were considered for this report. All received hypofractionated post-operative radiotherapy with a concomitant boost (45 Gy/20 fractions to the whole breast and 50 Gy/20 fractions to the lumpectomy cavity). We report on LC rates at 5 and 10 years, overall survival (OS), and breast-cancer-specific survival (BCSS), employing the Kaplan-Meier method. Cox proportional regression analysis was used to determine the role of selected clinical parameters on the risk of local recurrence, by the univariate and multivariate models. After a median follow-up of 11.2 years (range 5-15 years), 9 pts (11%) developed LR. The LR rates at 5 years and 10 years were 2.4% and 8.2%, respectively. The 5- and 10-year overall survival rates were 98.8% and 91.6%, respectively. The 5- and 10-year breast-cancer-specific survival rates were 100.0% and 99.0%. Late skin and subcutaneous toxicities were generally mild, and cosmetic results were good-excellent for most patients. For the univariate regression analysis, ER positive status (HR; 95% CI, p = 0.021), PgR positive status (HR; 95% CI, p = 0.012), and the aggregate data of positive hormonal status (HR; 95% CI, p = 0.021) were inversely correlated to LR risk. Conversely, a high tumor grade (G3) was directly correlated with the risk of LR (HR; 95% CI, p = 0.048). For the multivariate regression analysis, a high tumor grade (G3) confirmed its negative impact on LR (HR 0.40; 95% CI 0.19-0.75, p = 0.047). Our long-term data demonstrate hypofractionated whole-breast radiotherapy with a concomitant boost to be feasable, effective, and tolerable. Our experience suggests positive hormonal status to be protective with respect to LR risk. A high tumor grade is a risk factor for LR.

Effect of delaying surgery by more than 10 weeks after neoadjuvant therapy in rectal cancer: a single institution experience.

The optimal timing of surgery after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is still controversial. Aim of this study was to evaluate the effect of increasing time interval between the end of CRT and surgery on pathological outcomes. This is a retrospective analysis on 114 patients treated with long-course neoadjuvant RT with or without chemotherapy between January 2005 and September 2020. 43 patients underwent surgery within 10 weeks from the end of CRT (1st group), whereas 71 patients underwent total mesorectal excision with a time interval equal or greater than 10 weeks (2nd group). Primary endpoint was pCR (pathological complete response). Secondary endpoints were near pCR (ypT0-1 N0), tumor downstaging (ypT less than cT), nodal downstaging (ypN less than cN), and overall response comparing clinical with pathological TN stage. Overall, the pCR rate was 8.8%, whereas we observed no significantly difference in primary endpoint between the two groups. Considering near pCR, a trend toward significant difference in favor of 2nd group was seen (p = 0.072). Tumor and nodal downstaging rates were 39.5%, 41.9%, 59.2%, and 56.3% in the 1st and 2nd group, respectively, with a statistically significant difference for T category (p = 0.042). Overall response rates (TN stage) showed a trend toward significant difference in favor of patients of the ≥ 10 week group (p = 0.059). Our study suggests that a prolonged time interval between the end of CRT and surgery (≥ 10 weeks) increases pathological response rates.

Treatment Volume, Dose Prescription and Delivery Techniques for Dose-intensification in Rectal Cancer: A National Survey.

BACKGROUND/AIM: The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification. PATIENTS AND METHODS: An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment). RESULTS: Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%). CONCLUSION: A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols.

Moderately Hypofractionated Radiotherapy with Simultaneous Integrated Boost in Prostate Cancer: A Comparative Study with Conventionally Fractionated Radiation.

BACKGROUND: To report 5-year clinical outcomes and toxicity in organ-confined prostate cancer (PCa) for low- and intermediate-risk patients treated with a moderately hypofractionated schedule of radiotherapy (RT) delivered with simultaneous integrated boost (SIB) compared to a conventionally fractionated RT regimen. METHODS: Data of 384 patients with PCa treated between August 2006 and June 2017 were retrospectively reviewed. The treatment schedule consisted of hypofractionated RT (HYPO FR) with SIB up to 70 Gy to the prostate gland and 63 Gy to seminal vesicles delivered in 28 fractions or in conventionally fractionated RT (CONV FR) up to a total dose of 80 Gy in 40 fractions. Patient allocation to treatment was based on the time period considered. For intermediate-risk patients, androgen deprivation was given for a median duration of 6 months. The 5-year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), and overall survival (OS) were assessed. Furthermore, we evaluated gastrointestinal (GI) and genitourinary (GU) toxicities. Uni- and multivariate Cox regression analyses were used to test the impact of clinical variables on both outcome and toxicity. RESULTS: A total of 198 patients was treated with hypofractionated RT and 186 with the conventional schedule. At a median follow-up of 5 years, no significant differences were observed in terms of GI toxicity and outcome between the two groups. Early GU toxicity was significantly increased in HYPO FR, while late GU toxicity was significantly higher in CONV FR. In HYPO FR, a biochemical relapse occurred in 12 patients (6.1%), and 9 patients (4.5%) reported a clinical relapse (4 local, 2 locoregional, and 3 systemic recurrence). In CONV FR, 15 patients (8.1%) experienced a biochemical relapse and 11 patients (5.9%) showed a clinical relapse (5 local, 4 locoregional, and 3 systemic recurrences). Early grades 1-2 GU and GI toxicities were observed in 60 (30.3%) and 37 (18.7%) patients, respectively, in the hypofractionated group and in 33 (17.7%) and 27 (14.5%) patients, respectively, in the conventionally fractionated RT group. Late GU and GI toxicities occurred in 1 (0.51%) and 8 (4.1%) patients, respectively, in HYPO FR. In CONV FR, 5 (2.7%) and 6 (3.2%) patients experienced late GU and GI toxicities, respectively. The 5-year OS, bRFS, and CSS were 98.9%, 94.1%, and 99.5%, respectively, in HYPO FR, and 94.5%, 92.1%, and 99.0%, respectively, in CONV FR. CONCLUSIONS: Results obtained in this study showed that moderately hypofractionated RT employing SIB can be an effective approach providing valuable clinical outcomes with an acceptable toxicity profile.

Olfactory neuroblastoma treated with minimally invasive surgery and adjuvant radiotherapy: a case report and review of the literature.

Olfactory neuroblastoma (ON) is a rare tumour of the olfactory neuroepithelium that is characterized by a pattern of slow growth and local recurrences. Combination of surgery and radiotherapy, with or without chemotherapy, is considered to be the standard of care for primary site disease. Recent literature supports the view that endoscopic resection followed by adjuvant radiotherapy correlates with better outcome. In this short communication, we present a case report of olfactory neuroblastoma arising in the right nasal sinus in a 34-year-old male. This patient was treated with endoscopic resection and external beam radiotherapy to the right nasal sinus with intensity-modulated radiation therapy (IMRT) technique. After 2 years follow-up, the patient is free of tumour without any late effect related to therapies. We believe that, in such patients, a treatment strategy including endoscopic resection followed by adjuvant radiotherapy may be effective and feasible and should be considered the gold standard of care.

Variability of clinical target volume delineation for rectal cancer patients planned for neoadjuvant radiotherapy with the aid of the platform Anatom-e.

OBJECTIVE: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. MATERIALS AND METHODS: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). RESULTS: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58-0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67-0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85-4.78) than without (4.14; SD: ±2.97; range: 2.18-5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08-32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14-48.72). CONCLUSIONS: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols.

Correction to: Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer.

An error inadvertently occurred in the discussion of the original publication when citing the local relapse rates of the EORTC 22881-10882 trial ('boost vs no boost trial').

Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer.

Accelerated hypofractionated whole-breast radiotherapy (WBRT) is considered a standard therapeutic option for early breast cancer (EBC) in the postoperative setting after breast conservation (BCS). A boost to the lumpectomy cavity may further increase local control. We herein report on the 10-year results of a series of EBC patients treated after BCS with hypofractionated WBRT with a concomitant photon boost to the surgical bed over 4 weeks. Between 2005 and 2007, 178 EBC patients were treated with a basic course of radiotherapy consisting of 45 Gy to the whole breast in 20 fractions (2.25 Gy daily) with an additional boost dose of 0.25 Gy delivered concomitantly to the lumpectomy cavity, for an additional dose of 5 Gy. Median follow-up period was 117 months. At 10-year, overall, cancer-specific, disease-free survival and local control were 92.2% (95% CI 88.7-93.4%), 99.2% (95% CI 96.7-99.7%), 95.5% (95% CI 91.2-97.2%) and 97.3% (95% CI 94.5-98.9%), respectively. Only eight patients recurred. Four in-breast recurrences, two axillary node relapses and two metastatic localizations were observed. Fourteen patients died during the observation period due to other causes while breast cancer-related deaths were eight. At last follow-up, ≥G2 fibrosis and telangiectasia were seen in 7% and 5% of patients. No major lung and heart toxicities were observed. Cosmetic results were excellent/good in 87.8% of patients and fair/poor in 12.2%. Hypofractionated WBRT with concomitant boost to the lumpectomy cavity after BCS in EBC led to consistent clinical results at 10 years. Hence, it can be considered a valid treatment option in this setting.

The role of radiation therapy in vulvar cancer: review of the current literature.

The purpose of this article is to discuss the current role of radiation therapy in vulvar cancer and especially to review the recent literature relative to the use of intensity-modulated radiotherapy (IMRT) in disease management. Owing to the low incidence of vulvar cancer, at present there are no available results of cooperative prospective trials. As evidenced in dosimetric and preliminary retrospective clinical studies, the use of IMRT has resulted in superior normal tissue sparing and lower rates of acute and chronic toxicities compared to previous studies that used conventional approaches. Data on long-term outcomes in these patients remain limited.

Potential Benefit of Involved-Field Radiotherapy for Patients With Relapsed-Refractory Hodgkin's Lymphoma With Incomplete Response Before Autologous Stem Cell Transplantation.

INTRODUCTION: We investigated for a possible role for peritransplantation involved-field radiotherapy (IFRT) by comparing patients who received IFRT before after autologous stem cell transplantation (ASCT) and patients who received salvage chemotherapy (CT) alone. PATIENTS AND METHODS: We retrospectively evaluated 73 consecutive patients with Hodgkin lymphoma treated with ASCT between 2003 and 2014. Twenty-one patients (28.8%) received peritransplantation radiotherapy. A Cox regression analysis (multivariate analysis; MVA) was performed to evaluate the prognostic role of any risk factor. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of ASCT. Response to CT and ASCT were evaluated with positron emission tomography (PET) scan. RESULTS: Median follow-up was 41 months (range, 1-136 months). Overall, no significant difference appeared between patients who received IFRT and patients treated with CT alone; however, patients who were treated with IFRT had worse prognostic factors. In the MVA, advanced stage at relapse and persistent disease before ASCT (evident on PET scan [PET+]) were related to worse PFS and OS. In patients with limited stage disease at relapse and PET+, peritransplantation radiotherapy showed higher 3-year OS rates (91.7% vs. 62.3%) and PFS rates (67.5% vs. 50%) compared with patients treated with CT alone, although this difference was not significant (P = .14 and P = .22, respectively). CONCLUSION: IFRT used before or after ASCT might partially compensate for worse prognostic factors among the overall population; subgroup analysis showed a trend for survival benefit at 3 years in patients with limited stage disease at relapse and PET+ before ASCT.

Delineation of the larynx as organ at risk in radiotherapy: a contouring course within "Rete Oncologica Piemonte-Valle d'Aosta" network to reduce inter- and intraobserver variability.

AIMS: To evaluate the usefulness of a contouring course in reducing inter- and intraobserver variability in the definition of the larynx as organ at risk (OAR). METHODS: Within the "Rete Oncologica Piemonte-Valle d'Aosta" network, a contouring course focusing on larynx delineation was proposed. Twenty-six radiotherapist technicians (RTTs) experienced in delineating OARs were asked to contour larynx before and after the training. An expert radiation oncologist defined the reference volume for educational purpose. The contoured volumes obtained before and after the course were compared using descriptive statistics (mean value, standard deviation-SD, and coefficient of variation-COV) of volumes and maximum diameters. Conformity index (CI), dice coefficient (DC), and percentage of overlap were used to evaluate the spatial accuracy of the different volumes compared to the reference. Further analysis regarding the variation in the centre of mass (COM) displacement was performed. RESULTS: The mean volume was 40.4 cm3 before and 65.9 cm3 after the course, approaching the reference value. Mean anteroposterior, laterolateral, and craniocaudal diameters improved, getting each closer to the reference. Moreover, the COM moved approaching reference coordinates. Mean percentage of intersection and DC strongly increased after the course, rising from 57.76 to 93.83 % and from 0.68 to 0.89, respectively. CI enhanced from 0.06 to 0.31. CONCLUSIONS: This study shows an improvement in larynx definition after the contouring course with lower interobserver variability and major consistency compared to the reference volume. Other specific educational activities may further increase the quality of radiation therapy contouring in this setting.

Prognostic Role of Pre-Radiation Therapy (18)F-Fluorodeoxyglucose Positron Emission Tomography for Primary Mediastinal B-Cell Lymphomas Treated with R-CHOP or R-CHOP-Like Chemotherapy Plus Radiation.

PURPOSE: To validate, in a monoinstitutional cohort with extended follow-up, that post-rituximab chemotherapy (R-CT) (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) is a prognostic factor allowing discrimination of primary mediastinal B-cell lymphoma (PMBCL) patients at higher risk for progression after radiation therapy. METHODS AND MATERIALS: We analyzed 51 patients, and (18)FDG-PET scans were re-examined evaluating both the Deauville 5-point scale (D5PS) score and the standardized uptake value (SUV) of residual activity, if present. These parameters were then tested by univariate analysis for a potential correlation with progression-free survival (PFS) as the primary study endpoint. RESULTS: Median follow-up time was 51 months (range, 9-153 months). After R-CT, D5PS score was 1 in 10 (19.6%), 2 in 11 (21.6%), 3 in 7 (13.8%), 4 in 17 (33.3%), and 5 in 6 patients (11.7%). Forty-three out of 51 patients (84.3%) had an SUVmax ≤5, and 8 out of 51 (15.7%) had an SUVmax ≥5. Overall, 6 patients experienced progression or relapse: 1 had a D5PS score 2 (with SUVmax ≤5), and 5 had a D5PS score 5 (and SUVmax ≥5). Patients with a D5PS score 5 showed significantly lower PFS rates versus all other scores (log-rank P<.001), as did patients with SUVmax ≥5 when compared with those with SUVmax ≤5 (log-rank P<.001). CONCLUSIONS: The present study confirmed the prognostic role of (18)FDG-PET after R-CT, with patients with a D5PS score of 5 and/or an SUVmax ≥5 being at high risk of progression/relapse after RT.

Interobserver variability in clinical target volume delineation for primary mediastinal B-cell lymphoma.

PURPOSE: The purpose of this study was to evaluate interobserver variability among radiation oncologists with experience in the field of lymphoma radiation therapy in the delineation of clinical target volume (CTV) in a challenging case of primary mediastinal B-cell lymphoma. METHODS AND MATERIALS: Ten experienced radiation oncologists were invited to a 1-day contouring session. The case of a 56-year-old man with primary mediastinal B-cell lymphoma with complete metabolic response after chemotherapy was chosen as the sample for the study. A brief presentation of his clinical history was given, together with guidelines for contouring. The 10 CTVs obtained were then compared in terms of variation in total volume and in craniocaudal, laterolateral, and anteroposterior diameters. The CTV with the best Dice similarity coefficient (DSC) between the union of all 10 CTVs and the individual CTV was considered the reference CTV, and the DSC and the Hausdorff distance (HD) for each volume compared with the reference CTV were then calculated. RESULTS: A significant variability was found in total volume (mean, 498.3 cm(3); range, 181.8-1003 cm(3)) and craniocaudal (median, 144.7 mm; range, 80.6-159 mm), laterolateral (median, 133.5 mm; range, 83.7-149.5 mm), and anteroposterior diameters (median, 136.2 mm; range, 84-150.5 mm). Analysis of the DSC and the HD showed a mean DSC of 0.53 (range, 0.31-0.74) and a mean HD of 6.4 cm (range, 1.8-14.8 cm). CONCLUSIONS: Results of this study strongly indicate the need to develop and share appropriate contouring guidelines among experts and suggest the promotion of specific educational activities to improve radiation therapy quality in both clinical trials and routine clinical practice.

Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement: a comparison of second cancers and heart disease risk.

PURPOSE: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). RESULTS: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. CONCLUSIONS: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach.

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.

The Evolving Role of Radiotherapy in Early Stage Hodgkin's Lymphoma.

Radiation therapy has a key role in the combined modality treatment of early-stage Hodgkin's Lymphoma (HL). Nevertheless, late toxicity still remains an issue. A modern approach in HL radiotherapy includes lower doses and smaller fields, together with the implementation of sophisticated and dedicated delivery techniques. Aim of the present review is to discuss the current role of radiotherapy and its potential future developments, with a focus on major clinical trials, technological advances and their repercussion in the clinical management of HL patients.