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.

The dosimetric impact of axillary nodes contouring variability in breast cancer radiotherapy: An AIRO multi-institutional study.

AIM: To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT). MATERIALS AND METHODS: 18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed. RESULTS: 17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose. CONCLUSIONS: Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

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.

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.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

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.

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.

Image-guided Intensity-modulated Radiotherapy for Prostate Cancer Employing Hypofractionation and Simultaneous Integrated Boost: Results of a Consecutive Case Series with Focus on Erectile Function.

AIM: To report on clinical outcomes of prostate cancer patients treated with hypofractionated radiotherapy employing a simultaneous integrated boost strategy. PATIENTS AND METHODS: A consecutive series of 104 patients affected with prostate cancer was treated with intensity-modulated radiotherapy using a hypofractionated schedule and a simultaneous integrated boost consisting of 70 Gy (2.5 Gy daily) to the prostate gland, 63 Gy to the seminal vesicles (2.25 Gy daily) and 53.2 Gy to the pelvic nodes (1.9 Gy daily) when needed, delivered in 28 fractions. All patients underwent image-guided radiotherapy procedure consisting of daily cone-beam computed tomography. RESULTS: After a median observation time of 26 (range=15-48) months, the 3-year biochemical failure-free survival was 96.5% [95% confidence interval (CI)=89%-98%], 3-year cancer-specific survival was 98.5% (95% CI=91%-99%) and 3-year overall survival was 96.5% (95% CI=89%-98%). The gastrointestinal and genitourinary toxicity profiles were mild with fewer than 2% of grade 3 events. Erectile function was partially affected by radiation in men potent at baseline. CONCLUSION: Hypofractionation delivered with intensity-modulated radiotherapy and a simultaneous integrated boost approach proved to be a safe and effective treatment option for patients with prostate cancer. Patients with a preserved baseline erectile function experience a decrease in functionality correlated with the mean dose received by penile bulb.

Tumor Bed Boost Integration during Whole Breast Radiotherapy: A Review of the Current Evidence.

Radiation therapy delivered with hypofractionation, which involves the delivery of a higher dose per fraction in fewer fractions (generally with a lower total nominal dose) over a shorter overall treatment time, is an established therapeutic option at least for a selected group of early breast cancer patients after breast-conserving surgery. Optimal delivery of the tumor bed boost dose in terms of timing, fractionation, and total dose whenever a hypofractionated schedule is employed has yet to be established. We herein present a review of the current evidence on the role of boost integration in whole breast radiotherapy.

Bilateral breast radiation delivered with static angle tomotherapy (TomoDirect): clinical feasibility and dosimetric results of a single patient.

We herein report on a case of synchronous bilateral breast cancer patient undergoing adjuvant intensity-modulated whole breast with static angle tomotherapy (TomoDirect). The patient was treated with a hypofractionated schedule employing a simultaneous integrated boost approach. Radiotherapy schedule was 45 Gy/20 fractions (2.25 Gy daily) to the bilateral whole breast and 50 Gy/20 fractions (2.5 Gy daily) to the 2 lumpectomy cavities. Treatment was delivered over 4 weeks. Dosimetric results were robust with consistent target coverage and adequate normal tissue avoidance. Treatment was generally well-tolerated and acute toxicity profile was mild. The present report highlights the promising clinical feasibility of TomoDirect for bilateral breast irradiation.

Palliative radiotherapy for painful bone metastases from solid tumors delivered with static ports of tomotherapy (TomoDirect): feasibility and clinical results.

PURPOSE: To evaluate the feasibility and response to palliative radiotherapy delivered with static ports of tomotherapy--TomoDirect (TD) in patients affected with painful bone metastases from solid tumors. METHODS: A prospective cohort of 130 patients (185 osseous lesions) was treated between 2010 and 2013 with TD. Three fractionation schedules were employed according to clinical decision-making (3 Gy × 10; 4 Gy × 5; 8 Gy × 1). Pain response was investigated at 2 weeks and 2 months (for evaluable patients). The Numeric Rating Scale (NRS-11) was used to assess pain. Response rates to radiotherapy were calculated following the criteria of the International Bone Metastases Consensus Group (IBMCG), accounting for the use of concomitant analgesics (response: complete or partial; non-response: stable pain, pain progression or "other"). Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED). RESULTS: Most of the patients had 1-2 bone metastases (91); those with multiple lesions mostly had a metachronous presentation (60%). Synchronous lesions were mainly approached with multiple plans (63%). Most treatments employed 3-4 fields (77%). Treatment times ranged from 255 to 939 s depending on fractionation, fields, and target lesions number. At 2 weeks, the median self-reported worst pain decreased significantly as median oral morphine-equivalent dose regardless of fractionation used. The response rate according to the IBMCG-based response categories ranged from 45 to 55%. Pain relief duration seems (response at 2 months) slightly inferior with the single fraction approach, with a higher re-treatment rate. At 2 weeks, the median self-reported worst pain and OMED significantly decreased regardless of fractionation (response rate: 49-55%). Pain relief decreased at 2 months, especially for single fraction (higher re-treatment rate). CONCLUSION: TD is a valid option to deliver palliative radiotherapy for painful bone metastases from solid tumors.

Cerebellar glioblastoma multiforme in an adult woman.

AIMS AND BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent primary central nervous system malignancy in adults, accounting for 50% of all primary intracranial malignancies. GBM mostly arises within the cerebral hemispheres and frequently affects patients in the fifth and sixth decades of life. Conversely, primary cerebellar GBM is a rather infrequent occurrence in the adult population, accounting for 1%-2.2% of all GBMs. Here we report a case of cerebellar GBM in an adult woman and provide an extensive review of the literature. METHODS: A 42-year-old woman was referred to our hospital for occipital constrictive headache, dizziness and gait disturbance. Multimodality imaging including computed tomography and magnetic resonance imaging (MRI) showed a right cerebellar mass. Gross total resection was performed. Histological examination showed grade IV GBM according to the World Health Organization classification, with a synchronous component of low-grade glioma. Immunohistochemistry showed positivity for p53 and negativity for epidermal growth factor receptor (EGFR). After surgical tumor excision, the patient underwent adjuvant radiation to the posterior fossa with an intensity-modulated approach for a total dose of 60 Gy in 30 fractions. In addition, she received concurrent and adjuvant chemotherapy with temozolomide. RESULTS: Treatment was well tolerated, with mild acute toxicity. There was no evidence of recurrence on brain and spinal gadolinium-enhanced MRI scans 4, 8 and 12 months after primary surgery. No late side effects were recorded. CONCLUSION: Our patient had several immunohistochemical characteristics of secondary glioblastoma such as p53 positivity, EGFR negativity and the presence of a low-grade glioma component. Intensity-modulated radiation therapy allowed us to safely deliver full-dose radiation with sparing of critical structures.

Minimizing a tricky situation in breast irradiation with helical tomotherapy.

We report on a patient with breast cancer undergoing adjuvant intensity-modulated whole breast and lymph node irradiation with static angle tomotherapy (TomoDirect), who experienced a traumatic ipsilateral humeral fracture and was able to continue radiotherapy with helical tomotherapy and daily dosimetric monitoring by means of the Planned Adaptive module.

Penile metastasis from prostate cancer: a case report.

Metastatic involvement of the penis is rare. About 80% of secondary lesions originate from pelvic primary tumors, mainly bladder and prostate. We present a case of prostatic mucinous adenocarcinoma with penile metastasis symptomatic for pain, which was treated with external-beam radiation (35 Gy/14 fractions; 2.5 Gy daily) combined with androgen deprivation, resulting in complete pain relief and objective response after treatment.

Hypofractionation and concomitant boost to deliver adjuvant whole-breast radiation in ductal carcinoma in situ (DCIS): a subgroup analysis of a prospective case series.

To report the four-year outcomes of accelerated hypofractionated whole-breast radiotherapy (WBRT) with a concomitant boost (CB) to the tumor bed in ductal carcinoma in situ (DCIS), we performed a subgroup analysis of 103 patients affected with DCIS within a cohort of 960 early breast cancer patients treated with breast conservation and hypofractionated WBRT. Prescription dose to the whole breast was 45 Gy (2.25 Gy/20 fractions) with an additional daily CB of 0.25 Gy to the surgical cavity (2.5 Gy/20 fractions up to 50 Gy). With a median follow-up of 48 months (range 12-91), no local recurrence was observed. Maximum detected acute skin toxicity was as follows: G0 in 35 % of patients, G1 in 54 %, G2 in 9 % and G3 in 2 %. Late skin and subcutaneous toxicity were generally mild with only 1 % of patients experiencing ≥G3 events (telangiectasia). No major lung and heart toxicity were detected. Cosmetic results were excellent in 50 % of patients, good in 37 %, fair in 9 % and poor in 4 %. Quality of life had a generally favorable profile both within the functioning and symptoms domains. The present result supports the hypothesis that DCIS patients could be safely treated with a hypofractionated schedule employing a CB to the lumpectomy cavity.

Intensity-modulated and hypofractionated simultaneous integrated boost adjuvant breast radiation employing statics ports of tomotherapy (TomoDirect): a prospective phase II trial.

PURPOSE: To report the 1-year outcomes of a prospective phase II study on hypofractionated whole-breast intensity-modulated radiotherapy (IM-WBRT) with a simultaneous integrated boost (SIB) to the tumor bed delivered with static ports of tomotherapy (TomoDirect) (TD). METHODS: A prospective cohort of 82 patients was enrolled between 2011 and 2012. Treatment schedule consisted of 45 Gy/20 fractions to the whole breast and 50 Gy/20 fractions to the surgical bed delivered concomitantly with TD over 4 weeks. A one-armed optimal two-stage Simon's design was selected to test the hypothesis that treatment modality under investigation would decrease acute skin toxicity over historical data using conventional fractionation and sequential boost. Primary endpoint was acute skin toxicity. Secondary endpoints included late toxicity, cosmesis, quality of life and local control. RESULTS: Median follow-up was 12 months (range 6-18). Maximum detected acute skin toxicity was G0 41 %; G1 53 %; G2 6 %; G3 <1 %. With two G2-G3 acute skin toxicity events in the first stage and four in the second, the study fulfilled the requirements for the definition of the treatment approach under investigation as promising. Late skin toxicity was mild with no >G2 events. Cosmesis was good/excellent in 91 % of patients and fair/poor in 9 %. Quality of life was preserved over time, with the exception of fatigue, which was transiently increased. CONCLUSIONS: Hypofractionated IM-WBRT with a SIB to the tumor bed delivered with TD provides consistent clinical results and it is able to reduce acute skin toxicity rate over conventionally fractionated and sequential boost tomotherapy-based IM-WBRT.

Management of 'in-field' skin toxicity in head and neck cancer patients treated with combined cetuximab and radiotherapy.

It is well known that the cetuximab (Cet) epidermal growth factor receptor (EGFR) antibody enhances the sensitivity of tumour cells to radiation, and it is likely that the concurrent administration of Cet and radiotherapy (RT) results in some degree of interplay between the effects of the individual agents on the skin and in the exacerbation of reactions normally seen with these individual agents. In this paper, we present a concise review of Cet/RT-related skin toxicity, focusing on mechanisms and pathogenesis, clinical presentation and scoring systems and, finally, therapeutic management.