Stereotactic Radiotherapy for Brain Metastases: Imaging Tools and Dosimetric Predictive Factors for Radionecrosis

Radionecrosis (RN) is the most important side effect after stereotactic radiotherapy (SRT) for brain metastases, with a reported incidence ranging from 3% to 24%. To date, there are no unanimously accepted criteria for iconographic diagnosis of RN, as well as no definitive dose-constraints correlated with the onset of this late effect. We reviewed the current literature and gave an overview report on imaging options for the diagnosis of RN and on dosimetric parameters correlated with the onset of RN. We performed a PubMed literature search according to the preferred reporting items and meta-analysis (PRISMA) guidelines, and identified articles published within the last ten years, up to 31 December 2019. When analyzing data on diagnostic tools, perfusion magnetic resonance imaging (MRI) seems to be very useful allowing evaluation of the blood flow in the lesion using the relative cerebral blood volume (rCBV) and blood vessel integrity using relative peak weight (rPH). It is necessary to combine morphological with functional imaging in order to match information about lesion morphology, metabolism and blood-flow. Eventually, serial imaging follow-up is needed. Regarding dosimetric parameters, in radiosurgery (SRS) V12 < 8 cm3 and V10 < 10.5 cm3 of normal brain are the most reliable prognostic factors, whereas in hypo-fractionated stereotactic radiotherapy (HSRT) V18 and V21 are considered the main predictive independent risk factors of RN

Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis

Background: To date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy. Materials and methods: 76 patients were retrospectively analyzed. A total dose of 60 Gy (20 x 3 Gy) or 67.5 Gy (25 x 2.7 Gy) was prescribed. The Chi2 test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis. Results: median follow-up was 42.26 months [interquartile (IQR), 23–76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57–34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013). Conclusions: HT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa

Dose-escalated pelvic radiotherapy for prostate cancer in definitive or postoperative setting

Purpose Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. Methods Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. Results ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220-0.7647, P = 0.0113), while total dose < 60 Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245-9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338-2.169, P = 0.743, and HR = 2.39, 95% CI 0.93-6.111, P = 0.067, respectively). Conclusion Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes

Radiotherapy at oligoprogression for metastatic castration-resistant prostate cancer patients: a multi-institutional analysis

Purpose To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). Materials and methods mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan-Meier method; univariate and multivariate analyses were performed. Results Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1-44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade >= 2 toxicity. Conclusion Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed

Stereotactic radiotherapy for lung oligometastases

30–60% of cancer patients develop lung metastases, mostly from primary tumors in the colon-rectum, lung, head and neck area, breast and kidney. Nowadays, stereotactic radiotherapy (SRT) is considered the ideal modality for treating pulmonary metastases. When lung metastases are suspected, complete disease staging includes a total body computed tomography (CT) and/or positron emission tomography-computed tomography (PET-CT) scan. PET-CT has higher specificity and sensitivity than a CT scan when investigating mediastinal lymph nodes, diagnosing a solitary lung lesion and detecting distant metastases. For treatment planning, a multi-detector planning CT scan of the entire chest is usually performed, with or without intravenous contrast media or esophageal lumen opacification, especially when central lesions have to be irradiated. Respiratory management is recommended in lung SRT, taking the breath cycle into account in planning and delivery. For contouring, co-registration and/or matching planning CT and diagnostic images (as provided by contrast enhanced CT or PET-CT) are useful, particularly for central tumors. Doses and fractionation schedules are heterogeneous, ranging from 33 to 60 Gy in 3–6 fractions. Independently of fractionation schedule, a BED10 &gt; 100 Gy is recommended for high local control rates. Single fraction SRT (ranges 15–30 Gy) is occasionally administered, particularly for small lesions. SRT provides tumor control rates of up to 91% at 3 years, with limited toxicities. The present overview focuses on technical and clinical aspects related to treatment planning, dose constraints, outcome and toxicity of SRT for lung metastases.

Effect of internal port on dose distribution in post-mastectomy radiotherapy for breast cancer patients after expander breast reconstruction

Background: In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at adding data on this field. Materials and methods: A dosimetric analysis was conducted in 30 chest wall treatment planning without and with correction for port artifact. In plans with artifact correction density was overwritten as 1 g/cm3. Medium, minimum and maximum chest wall doses were compared in the two plans. Both plans, with and without correction, were compared on an anthropomorphic phantom with a tissue expander on the chest covered by a bolus simulating the skin. Ex vivo dosimetry was carried out on the phantom and in vivo dosimetry in three patients by using film strips during one treatment fraction. Estimated doses and measured film doses were compared. Results: No significant differences emerged in the minimum, medium and maximum doses in the two plans, without and with correction for port artifacts. Ex vivo and in vivo analyses showed a good correspondence between detected and calculated doses without and with correction. Conclusions: The port did not significantly affect dose distribution in patients who will receive post-mastectomy radiation therapy (PMRT)

Recommendations for radiation therapy in oligometastatic prostate cancer:An ESTRO-ACROP Delphi consensus

Background and purpose: Oligometastatic prostate cancer is a new and emerging treatment field with only few prospective randomized studies published so far. Despite the lack of strong level I evidence, metastasis-directed therapies (MDT) are widely used in clinical practice, mainly based on retrospective and small phase 2 studies and with a large difference across centers. Pending results of ongoing prospec-tive randomized trials, there is a clear need for more consistent treatment indications and radiotherapy practices.Material and methods: A European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee consisting of radiation oncologists' experts in prostate cancer was asked to answer a dedicated question-naire, including 41 questions on the main controversial issues with regard to oligometastatic prostate cancer.Results: The panel achieved consensus on patient selection and routine use of prostate-specific mem-brane antigen positron emission tomography (PSMA PET) imaging as preferred staging and restaging imaging. MDT strategies are recommended in the de novo oligometastatic, oligorecurrent and oligopro-gressive disease setting for nodal, bone and visceral metastases. Radiation therapy doses, volumes and techniques were discussed and commented.Conclusion: These recommendations have the purpose of providing standardization and consensus to optimize the radiotherapy treatment of oligometastatic prostate cancer until mature results of random-ized trials are available.AT would like to acknowledge the support of Cancer Research UK (C33589/A28284 and C7224/A28724) . This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care

Choline PET/CT in recurrent prostate cancer

PurposeBiochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Methods/patientsPatients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes.ResultsData from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS).ConclusionCholine PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life