Patients' needs in proton therapy: A survey among ten European facilities.

Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients' logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10-30%, 30-50% and 50-70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country's Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient's access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

Phantom study of stereotactic radioablation for ventricular tachycardia (STRA-MI-VT) using Cyberknife Synchrony Respiratory Tracking System with a single fiducial marker.

PURPOSE: Within the STRA-MI-VT phase Ib/II trial (NCT04066517), the aim of this phantom study was to explore the feasibility of Cyberknife treatments on cardiac lesions by tracking as a single marker the lead tip of an implantable cardioverter defibrillator. The residual displacement of the lesion during the tracking was studied, planning margins were found and the dosimetric accuracy of the treatment was checked. MATERIALS AND METHODS: A lead was inserted into a phantom (EasyCube phantom, Sun Nuclear Co, USA) and then placed on the translating ExacTrac Gating System (BrainLAB AG, Germany). The phantom was rotated, a virtual lesion was identified and its displacement during the tracking was studied. Two plans were compared, calculated on the unrotated volume and on the envelope of the unrotated and the rotated volumes. The plans were delivered using the Cyberknife System (Accuray Inc, USA) and their dosimetric accuracy verified by gamma analysis with gafchromic films. RESULTS: The residual margin increases enhancing the distance between the lead and the lesion. It is 4 mm for distance 0 cm and 5 mm for distance 5 cm. The coverage is reduced by 3.8% (interquartile range 2.5%-4.7%) when the dose is prescribed on the unrotated volume. All treatment plans are accurate and 3% 3 mm gamma analysis results are greater than 94%. CONCLUSIONS: Results showed that tracking with a single marker is feasible considering adequate residual planning margins. The volumes could be further reduced by using additional markers, for example by placing them on the patient's skin.

Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM).

The Italian Association of Medical Oncology recommendations on thymic epithelial tumors, which have been drawn up for the first time in 2020 through an evidence-based approach, report indications on all the main aspects of clinical management of this group of rare diseases, from diagnosis and staging, to new available systemic treatments, such as targeted therapies and immunotherapies. A summary of key recommendations is presented here and complete recommendations are reported as Supplementary Materials, available at https://doi.org/10.1016/j.esmoop.2021.100188.

Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Seroconversion in patients with cancer and oncology health care workers infected by SARS-CoV-2.

BACKGROUND: Patients with cancer have high risk for severe complications and poor outcome to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease [coronavirus disease 2019 (COVID-19)]. Almost all subjects with COVID-19 develop anti-SARS-CoV-2 immunoglobulin G (IgG) within 3 weeks after infection. No data are available on the seroconversion rates of cancer patients and COVID-19. PATIENTS AND METHODS: We conducted a multicenter, observational, prospective study that enrolled (i) patients and oncology health professionals with SARS-CoV-2 infection confirmed by real-time RT-PCR assays on nasal/pharyngeal swab specimens; (ii) patients and oncology health professionals with clinical or radiological suspicious of infection by SARS-CoV-2; and (iii) patients with cancer who are considered at high risk for infection and eligible for active therapy and/or major surgery. All enrolled subjects were tested with the 2019-nCoV IgG/IgM Rapid Test Cassette, which is a qualitative membrane-based immunoassay for the detection of IgG and IgM antibodies to SARS-CoV-2. The aim of the study was to evaluate anti-SARS-CoV-2 seroconversion rate in patients with cancer and oncology health care professionals with confirmed or clinically suspected COVID-19. RESULTS: From 30 March 2020 to 11 May 2020, 166 subjects were enrolled in the study. Among them, cancer patients and health workers were 61 (36.7%) and 105 (63.3%), respectively. Overall, 86 subjects (51.8%) had confirmed SARS-CoV-2 diagnosis by RT-PCR testing on nasopharyngeal swab specimen, and 60 (36.2%) had a clinical suspicious of COVID-19. Median time from symptom onset (for cases not confirmed by RT-PCR) or RT-PCR confirmation to serum antibody test was 17 days (interquartile range 26). In the population with confirmed RT-PCR, 83.8% of cases were IgG positive. No difference in IgG positivity was observed between cancer patients and health workers (87.9% versus 80.5%; P = 0.39). CONCLUSIONS: Our data indicate that SARS-CoV-2-specific IgG antibody detection do not differ between cancer patients and healthy subjects.

STRA-MI-VT (STereotactic RadioAblation by Multimodal Imaging for Ventricular Tachycardia): rationale and design of an Italian experimental prospective study.

BACKGROUND: Ventricular tachycardia (VT) is a life-threatening condition, which usually implies the need of an implantable cardioverter defibrillator in combination with antiarrhythmic drugs and catheter ablation. Stereotactic body radiotherapy (SBRT) represents a common form of therapy in oncology, which has emerged as a well-tolerated and promising alternative option for the treatment of refractory VT in patients with structural heart disease. OBJECTIVE: In the STRA-MI-VT trial, we will investigate as primary endpoints safety and efficacy of SBRT for the treatment of recurrent VT in patients not eligible for catheter ablation. Secondary aim will be to evaluate SBRT effects on global mortality, changes in heart function, and in the quality of life during follow-up. METHODS: This is a spontaneous, prospective, experimental (phase Ib/II), open-label study (NCT04066517); 15 patients with structural heart disease and intractable VT will be enrolled within a 2-year period. Advanced multimodal cardiac imaging preceding chest CT-simulation will serve to elaborate the treatment plan on different linear accelerators with target and organs-at-risk definition. SBRT will consist in a single radioablation session of 25 Gy. Follow-up will last up to 12 months. CONCLUSIONS: We test the hypothesis that SBRT reduces the VT burden in a safe and effective way, leading to an improvement in quality of life and survival. If the results will be favorable, radioablation will turn into a potential alternative option for selected patients with an indication to VT ablation, based on the opportunity to treat ventricular arrhythmogenic substrates in a convenient and less-invasive manner.

Association of quantitative MRI-based radiomic features with prognostic factors and recurrence rate in oropharyngeal squamous cell carcinoma.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Adjuvant radiotherapy treatment for soft tissue sarcoma of extremities and trunk. A retrospective mono-institutional analysis.

Soft tissue sarcomas (STS) are uncommon, heterogeneous malignant tumors of mesodermal origin. Other than conservative surgery (CS), neoadjuvant or adjuvant radiotherapy (RT) is recommended when the risk of local recurrence is high. The aim of this study is to present our Institutional experience in adjuvant RT for treatment of STS of extremities and trunk (with either brachytherapy (BRT), external beam RT (EBRT), or both) and to provide an insight of toxicity and oncological outcomes for each RT modality. According to the RT treatment approach, patients were divided into three categories: 1) BRT alone; 2) EBRT alone; 3) combined BRT+EBRT. Differences among the three groups were assessed by the Chi-squared test. Patients' follow-up was performed every 6 months for the first two years after the end of RT and then once a year. Data from 90 patients were analyzed. The overall 3-year distant relapse-free survival (DRFS), progression-free survival (PFS), and overall survival (OS) were 84%, 80%, and 97%, respectively. Acute erythema was the most frequent side effect, although severe grade 3 toxicity was present in 5 patients. Chronic toxicity of any grade was reported in 14 patients. The incidence of chronic toxicity did not show any association with treatment modality. Multivariate analysis suggested a significant correlation between acute toxicity and tumor size, RT modality, and RT dose. In conclusion, good local control and toxicity profile were observed, despite negative patients' selection at baseline. Further investigation on wider series is warranted in order to define the optimal combination with systemic therapy.

Lung optimized treatment with CyberKnife® in inoperable lung cancer patients: feasibility analysis of a mono-institutional 115 patient series.

CyberKnife® Lung Optimized Treatment (LOT) allows the treatment of lung cancer without invasive fiducial implantation. The aim of this retrospective analysis was to evaluate the feasibility, toxicity and clinical outcome. One hundred fifteen patients (124 lesions) were treated with CyberKnife® using LOT. The median age was 72.6 years (range 31.8-90.3). From 124 treated lesions, 52 were with histopathological confirmation (41 primitive pulmonary cancers, 8 pulmonary metastases) and 72 as untyped tumors. For 5 patients (6 lesions) treatment was an in-field re-irradiation. Concomitant therapy was administered in 7 patients. Zero-View tracking was applied in 69 patients, 1-View in 33 patients, 2-View in 22 patients. The median total dose was 45 Gy (range 18-54), median dose/fraction was 15 Gy (range 4-18) with a median prescription isodose of 80% (range 68-85). The median planning target volume (PTV) was 25 cm3 (range 3-195). The median follow-up was 20 months (range 7-47). Thirty-seven patients (32%) were alive with no evidence of disease, 39 patients (34%) were alive with clinically evident disease, and 38 patients (33%) died of the disease. The 1- and 2-year overall survival (OS) rate was 83% and 61%. The median time to progression was 19 months (95% confidence interval: 11-19 months), 1- and 2-year progression-free survival (PFS) rates were 62% and 41%, respectively. Smaller PTV was significantly associated with better OS, PFS and in-field PFS in univariate and multivariate analyses. Acute toxicity was observed in 36 patients (41%). Late toxicity was registered in 25 patients (29%). G3 late toxicity was observed in one patient (1.1%). Our data suggest that fiducial less-stereotactic body radiation therapy (SBRT) is a feasible, well-tolerated and potentially effective treatment with high compliance in the setting of inoperable patients due to concomitant disease or previous treatments.

Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO.

AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

International multidisciplinary expert panel consensus on breast reconstruction and radiotherapy.

BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.

ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.

Stereotactic radiation therapy in oligometastatic colorectal cancer: outcome of 102 patients and 150 lesions.

To evaluate the local control (LC), progression free survival (PFS), out-field PFS, overall survival (OS), toxicity and failure predictors of SRT in a series of various sites oligometastatic CRC patients. Patients with oligometastatic CRC disease were analyzed retrospectively. The SRT prescribed dose was dependent on the lesion volume and its location. 102 consecutive oligometastatic CRC patients (150 lesions) were included. They underwent SRT between 2012 and 2015. Median prescription dose was 45 Gy (median dose/fraction was 15 Gy/3 fractions biological equivalent dose (BED10) 112.5 Gy). Median follow-up was 11.4 months. No patients experienced G3 and G4 toxicity. No progression was found in 82% (radiological response at 3 months) and 85% (best radiological response) out of 150 evaluable lesions. At 1 and 2 years: LC was 70% and 55%; OS was 90% and 90%; PFS was 37% and 27%; out-field PFS was 37% and 23% respectively. Progressive disease was correlated with BED10 (better LC when BED10 was ≥ 75 Gy (p < 0.0001)). In multivariate analysis, LC was higher in lesions with a Plpnning target volume (PTV) volume < 42 cm3 and BED10 ≥ 75 Gy. Patients with Karnofsky performance status < 90 showed higher out-field progression. SRT is an effective treatment for patients with oligometastases from CRC. Its low treatment-associated morbidity and acceptable LC make of SRT an option not only in selected cases. Further studies should be focused to clarify which patient subgroup will benefit most from this treatment modality and to define the optimal dose to improve LC while maintaining low toxicity profile.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

Recurrent oligometastatic transitional cell bladder carcinoma: is there room for radiotherapy?

This paper presents a retrospective report on radiotherapy (RT) in the oligometastastic recurrence of bladder cancer. Thirteen patients treated for low-volume metastatic transitional cell urinary bladder carcinoma (TCC) were reviewed, with the primary endpoint to evaluate the safety and efficacy of RT, proposed as an alternative to systemic treatment and/or to defer commencement of systemic therapy. The inclusion criteria were: patients who received RT without other local/systemic therapy for oligometastatic TCC with lymph node, bone and lung lesions or local recurrence. Previous systemic therapy and surgery on the primary tumor were allowed in this tumor response, and toxicity evaluation and progression free-survival was also assessed. Thirteen patients with 21 lesions were treated with stereotactic body radiotherapy (SBRT) or conformal 3D radiotherapy (3D-CRT) between 2012 and 2017. All participants were discussed by a multidisciplinary urological board. The median age at RT was 68 years (range 50-80), the median Karnofsky performance status (KPS) was 90 (range 80-90) and the median interval between TCC diagnosis and commencement of RT on oligometastasis was 23 months (range 8-105). The median treatment dose was 25 Gy (range 20-36 Gy) given over a median of 5 fractions (range 3-10 fractions) with a median follow-up of 25 months (range 3-43 months). Imaging assessment was available for 20 lesions. The radiological progression of disease was registered in 9 patients at the median of 4.2 months from radiotherapy (range 1.9-18.8 months). This identified in-field and out-field progression in 6 patients and only out-field progression in the remaining 3. At last contact, 3 patients were alive with no evidence of disease, 3 had evidence of disease, 6 died of cancer-related disease and one died from another cause. No severe acute and late toxicity was observed. The literature contains no consistent data on TCC oligometastatic setting, but radiotherapy on lymph node, bone and/or lung oligo-recurrence from TCC offers durable disease control in a small number of patients with a very low toxicity profile. Further studies are required to establish the radiotherapy role in oligometastatic recurrent bladder cancer.

Case series on multiple prostate re-irradiation for locally recurrent prostate cancer: something ventured, something gained.

The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.

Impact of image guidance on toxicity and tumour outcome in moderately hypofractionated external-beam radiotherapy for prostate cancer.

To report toxicity and efficacy outcome of moderately hypofractionated image-guided external-beam radiotherapy in a large series of patients treated for prostate cancer (PCa). Between 10/2006 and 12/2015, 572 T1-T3N0M0 PCa patients received 70.2 Gy in 26 fractions at 2.7 Gy/fraction: 344 patients (60%) with three-dimensional conformal radiotherapy (3D-CRT) and 228 (40%) with intensity-modulated radiotherapy (IMRT). Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median age was 74 years (interquartile range 69-77). Compared with 3D-CRT, in IMRT group more high-risk patients (29% vs 18%; P = 0.002) and more high-volume target (75% vs 60%; P < 0.001) were included. Acute gastro-intestinal (GI) toxicity G > 1 were registered in 8% and in 11% IMRT and 3D-CRT patients, respectively, whereas late GI G > 1 were observed in 2% and 16% IMRT and 3D-CRT patients, respectively. Acute genito-urinary (GU) toxicity G > 1 were registered in 26% and 40% IMRT and 3D-CRT patients, respectively, whereas late GU G > 1 occurred in 5% IMRT and 15% 3D-CRT patients. Multivariate proportional hazard Cox models confirmed significantly greater risk of late toxicity with 3D-CRT compared to IMRT for GU > 1 (P = 0.004) and for GI > 1 (P < 0.001). With a median 4-year follow-up, overall survival (OS), clinical progression-free survival (cPFS) and biochemical PFS (bPFS) for the whole series were 91%, 92% and 91%, respectively. cPFS and bPFS were significantly different by risk groups. Multivariate Cox models for bPFS and cPFS showed no difference between irradiation techniques and a significant impact of risk group and initial PSA. Moderately hypofractionated radiotherapy is a viable treatment option for localized PCa with excellent tumour control and satisfactory toxicity profile. IMRT seems associated with a reduction in toxicity, whereas tumour control was equal between IMRT and 3D-CRT patients and depended mainly on the risk category.