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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background This study investigates the use of TomoDirectTM 3DCRT for whole breast adjuvant radiotherapy (AWBRT) that represents a very attractive treatment opportunity, mainly for radiotherapy departments without conventional Linacs and only equipped with helical tomotherapy units. Methods Plans were created for 17 breast cancer patients using TomoDirect in 3DCRT and IMRT modality and field-in-field 3DCRT planning (FIF) and compared in terms of PTV coverage, overdosage, homogeneity, conformality and dose to OARs. The possibility to define patient-class solutions for TD-3DCRT employment was investigated, correlating OARs dose constraints to patient specific anatomic parameters. Results TD-3DCRT showed PTV coverage and homogeneity significantly higher than TD-IMRT and FIF. PTV conformality was significantly better for FIF, while no differences were found between TD-3DCRT and TD-IMRT. TD-3DCRT showed mean values of the OARs dosimetric endpoints significantly higher than TD-IMRT; with respect to FIF, TD-3DCRT showed values significantly higher for lung V20Gy, mean heart dose and V25Gy, while contralateral lung maximum dose and contralateral breast mean dose resulted significantly lower. The Central Lung Distance (CLD) and the maximal Heart Distance (HD) resulted as useful clinical tools to predict the opportunity to employ TD-3DCRT: positive correlations were found between CLD and both V20Gy and mean lung dose and between HD and both V25Gy and the mean heart dose. TD-3DCRT showed a significantly shorter mean beam-on time than TD-IMRT. Conclusions The present study showed that TD-3DCRT and TD-IMRT are two feasible and dosimetrically acceptable treatment approach for AWBRT, with an optimal PTV coverage and adequate OARs sparing. Some concerns might be raised in terms of dose to organs at risks if TD-3DCRT is applied to a general population. A correct patients clusterization according to simple quantitative anatomic measures, would help to correctly allocate patients to the appropriate treatment planning strategy in terms of target coverage, but also of normal tissue sparing.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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'). [ABSTRACT FROM AUTHOR]

Background: Non-sinonasal neuroendocrine carcinomas (NSNECs) of the head and neck are considered an unfrequent clinico-pathological entity. Combined modality treatment represents an established therapeutic option for undifferentiated forms where distant metastasis is a common pattern of failure.Methods: We report on a case of NSNEC treated with sequential chemo-radiation consisting of 6 cycles of cisplatin and etoposide followed by loco-regional radiation to the head and neck and simultaneous prophylactic cranial irradiation to prevent from intracranial spread, delivered with helical tomotherapy with the 'hippocampal avoidance' technique in order to reduce neuro-cognitive late effects.Results: One year after the end of the whole combined modality approach, the patient achieved complete remission, with no treatment-related sub-acute and late effects.Conclusions: The present report highlights the importance of multidisciplinary management for NSNECs of the head and neck, as the possibility to achieve substantial cure rates with mild side effects with modern radiotherapy techniques. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice., Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations., Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders., Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

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').

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.

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., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

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.

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.

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.

Radiochromic film has become an important tool to verify dose distributions in highly conformal radiation therapy such as IMRT. Recently, a new generation of these films, EBT3, has become available. EBT3 has the same composition and thickness of the sensitive layer of the previous EBT2 films, but its symmetric layer configuration allows the user to eliminate side orientation dependence, which is reported for EBT2 films. The most important EBT3 characteristics have been investigated, such as response at high-dose levels, sensitivity to scanner orientation and postirradiation coloration, energy and dose rate dependence, and orientation dependence with respect to film side. Additionally, different IMRT fields were measured with both EBT3 and EBT2 films and evaluated using gamma index analysis. The results obtained show that most of the characteristics of EBT3 film are similar to the EBT2 film, but the orientation dependence with respect to film side is completely eliminated in EBT3 films. The study confirms that EBT3 film can be used for clinical practice in the same way as the previous EBT2 film.

Aim and Background: Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial., Materials and Methods: From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin., Results: The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II (21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs. 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04)., Conclusions: Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.

Metastatic brain tumors from colorectal cancer are relatively rare. In previous reports the incidence ranged from 1.9 to 3.5 percent of all metastatic brain tumors. In another recent article the cumulative incidence of brain metastasis was estimated at 1.2%. The prognosis for patients with even a single resectable brain metastasis is poor. This paper presents the case report of a 72-year-old woman with a solitary brain metastasis 16 years after a diagnosis of colorectal cancer. She remained asymptomatic for 16 years. The first sign of a secondary tumor was diplopia. Brain scan demonstrated a space-occupying lesion in the occipital area. A solitary tumor was removed by craniotomy. Histological examination showed that it was a metastasis from the intestinal primary tumor. The patient subsequently underwent whole brain radiotherapy for a total dose of 30 Gy in 10 fractions.