Robotic stereotactic body radiation therapy for tumours of the liver: Radiation-induced liver disease,incidence and predictive factors

PurposeRobotic stereotactic body radiation therapy is a new option to treated unresecable liver tumours. The objectives were to assess the tolerance of this technique, to identify predictive factors for toxicity and evaluate the efficiency of this treatment.Patients and methodsFrom June 2010 to November 2012, robotic stereotactic body radiation therapy was proposed for 56 patients with unresecable hepatocellular carcinomas (23 patients) or hepatic metastases (41 patients). Two or less hepatic lesions, lesion size under 75 mm and WHO score under 3 were selection criteria. The prescribed dose was 45 Gy/3 fractions or 60 Gy/3 fractions. The primary end-point was toxicity, using the radiation-induced liver disease definition and to identify predictive factors. Secondary end-points were in-field local control and overall survival.ResultsThe median follow-up was 12.5 months. The one-year local control rate and the one-year overall survival rate were 64% [CI95%: 48.2 to 76.5%] and 89% [CI95%: 76 to 95%], respectively. For patient treated with a total dose of 60 Gy, no one experienced recurrence. According to the definition we took, radiation-induced liver disease rate was 0 or 9%. A lesion size at least 35 mm was a predictive factor to liver toxicity (P = 0.01).ConclusionUsing robotic stereotactic body radiation therapy, the incidence of radiation-induced liver disease is weak and spontaneously reversible. Prospective studies are required to put in evidence other predictive factors of radiation-induced liver disease and confirm the optimal dose treatment.     

Stereotactic radiotherapy for large solitary brain metastases

PurposeTo assess effectiveness and toxicity levels of stereotactic radiation therapy without whole brain radiation therapy in patients with solitary brain metastases larger than 3 cm.Patients and methodsBetween June 2007 and March 2009, 12 patients received fractionated stereotactic radiation therapy and 24 patients underwent stereotactic radiosurgery. For the fractionated stereotactic radiation therapy group, 3 × 7.7 Gy were delivered to the planning target volume (PTV); median volume and diameter were 29.4 cm³ and 4.4 cm, respectively. For the stereotactic radiosurgery group, 14 Gy were delivered to the PTV; median volume and diameter were 15.6 cm³ and 3.7 cm, respectively.ResultsMedian follow-up was 218 days. For the fractionated stereotactic radiation therapy group, local control rates were 100% at 360 days and 64% at 720 days; for the stereotactic radiosurgery group, rates were 58% at 360 days and 48% at 720 days (P = 0.06). Median survival time was 504 days for the fractionated stereotactic radiation therapy group and 164 days for the stereotactic radiosurgery group (P = 0.049). Two cases of grade 2 toxicity were observed in the fractionated stereotactic radiation therapy group, and 6 cases of grade 1–2 toxicity, in the stereotactic radiosurgery group.ConclusionsThis study provides data to support that fractionated stereotactic radiation therapy without whole brain radiation therapy with a margin dose of 3 fractions of 7.7 Gy for treatment of solitary large brain metastases is efficient and well-tolerated. Because of the significant improvement in overall survival, this schedule should be assessed in a randomized trial.     

Comparison of passive-beam proton therapy,helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy

PurposeSecond cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy.Patients and methodsFourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30 Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20 Gy/10 Gy.ResultsMean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15 Gy with the V_20 Gy equal to 16.4%, compared to 19.7% for proton therapy (P = 0.01) or 22.4% with 3D conformal radiation therapy (P < 0.01). Volumes of lung receiving doses below 15 Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V_10 Gy = 37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10 Gy or more than 4 Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V_4 Gy representing more than a third of one breast volume with helical tomotherapy.ConclusionsHelical tomotherapy achieved a better protection to the lungs for doses above 15 Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.     

Hyaluronic acid spacer in focal prostate reirradiation: A single centre experience

PurposeThe optimal management of locally recurrent prostate cancer after curative radiotherapy is still unknown. In this study, we evaluated the preliminary results of reirradiation using stereotactic body radiotherapy for locally recurrent prostate cancer after initial definitive local radiotherapy.Materials and methodsBetween April 2016 and February 2019, 11 patients with recurrent disease at the previously irradiated prostate were treated. Local recurrence was detected by radiological with or without functional imaging modalities including prostate multiparametric/pelvic MRI or positron-emission tomography–computerised tomography with (⁶⁸Ga)-labelled prostate-specific membrane antigen performed after rising prostate specific antigen serum level during follow-up. All patients received stereotactic body radiotherapy to the recurrent nodule to a total dose of 30 Gy in five fractions. Hyaluronic acid spacer was injected between prostate and rectum in seven patients to decrease the rectal dose. Acute toxicity was evaluated by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was evaluated by using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema.ResultsAt the diagnosis, the median age was 64 years, and the mean prostate specific antigen serum concentration was 17.7 ng/mL. The median interval time between local recurrence and initial definitive radiotherapy was 63 months. Mean prostate specific antigen concentration nadir value during follow-up was 0.43 ng/mL. With a median follow up of 19 months, three patients developed either local or distant relapse. One patient had grade 3 acute rectal toxicity, and one patient had grade 2 late urinary toxicity. We did not observe any acute or late toxicity due to hyaluronic acid spacer injection.ConclusionReirradiation after local recurrence following initial definitive radiotherapy together with hyaluronic acid spacer use seems to be effective and safe.     

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases

PurposeThe objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS).Materials and methodsSeventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0.ResultsThe median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47–62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06–3.01; P = 0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77–15.27; P < 0.001) tumour volume (> 12cc vs. ≤ 12cc; HR, 1.84; 95% CI, 1.10–3.11; P = 0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19–0.70; P = 0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients.ConclusionWith acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤ 12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.     

Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate

PurposeImage-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility.Patients and methodsOver a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife^® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6 Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6 Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25 Gy and 11 patients five fractions of 6.25 Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1 cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2 cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients.ResultsThe tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4–113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment.ConclusionsIntraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.     

Ocular proton therapy,pencil beam scanning high energy proton therapy or stereotactic radiotherapy for uveal melanoma; an in silico study

PurposeIn radiotherapy, the dose and volumes of the irradiated normal tissues is correlated to the complication rate. We assessed the performances of low-energy proton therapy (ocular PT) with eye-dedicated equipment, high energy PT with pencil-beam scanning (PBS) or CyberKnife^R  -based stereotactic irradiation (SBRT).Material and methodsCT-based comparative dose distribution between external beam radiotherapy techniques was assessed using an anthropomorphic head phantom. The prescribed dose was 60 Gy_RBE in 4 fractions to a typical posterior pole uveal melanoma. Clinically relevant structures were delineated, and doses were calculated using radiotherapy treatment planning softwares and measured using Gafchromic dosimetry films inserted at the ocular level.ResultsPrecision was significantly better with ocular PT than both PBS or SBRT in terms of beam penumbra (80%–20%: laterally 1.4 vs. ≥ 10 mm, distally 0.8 vs. ≥ 2.5 mm). Ocular PT duration was shorter, allowing eye gating and lid sparing more easily. Tumor was excellent with all modalities, but ocular PT resulted in more homogenous and conformal dose compared to PBS or SBRT. The maximal dose to ocular/orbital structures at risk was smaller and often null with ocular PT compared to other modalities. Mean dose to ocular/orbital structures was also lower with ocular PT. Structures like the lids and lacrimal punctum could be preserved with ocular PT using gaze orientation and lid retractors, which is easier to implement clinically than with the other modalities. The dose to distant organs was null with ocular PT and PBS, in contrast to SBRT.Conclusionsocular PT showed significantly improved beam penumbra, shorter treatment delivery time, better dose homogeneity, and reduced maximal/mean doses to critical ocular structures compared with other current external beam radiation modalities. Similar comparisons may be warranted for other tumor presentations.     

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases

PurposeDespite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery.Patients and methodsFrom January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13–22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm³.ResultsThe 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41–98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8–13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P = 0.003) and use of anti-PD1 (P = 0.006). Median overall survival (OS) was 14 months (CI 95%: 11–NR). Total irradiated tumor volume < 2.1 cm³ was a positive predictive factor for overall survival (P = 0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade ≥ 3. Predictive factors of all grade toxicity were: female gender (P = 0.001) and previous treatment with MAPK (P = 0.05).ConclusionA long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.     

Cardiac substructures exposure in left-sided breast cancer radiotherapy: Is the mean heart dose a reliable predictor of cardiac toxicity?

PurposeThis study aimed to assess radiation dose distribution to cardiac subvolumes in left-sided breast cancer radiotherapy (LBCRT) and to clarify whether the mean heart dose (MHD) reliably reflects cardiac substructures exposure.Materials and methodsFifty women referred for adjuvant LBCRT were prospectively evaluated. All patients received 3D-conformal hypofractionated radiotherapy (40 Gy delivered in 15 fractions of 2.67 Gy ± boost of 13.35 Gy). Cardiac substructures were contoured using the F. Duane's cardiac atlas. Dose distribution to cardiac chambers, left main (LM), left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA)) was assessed. Dosimetric associations were analysed.ResultsThe mean MHD was 3.08 Gy (EQD2 = 3.67 Gy). The mean Dmean/Dmax LAD was 11.45 Gy (EQD2 = 13.64 Gy)/29.5 Gy (EQD2 = 35.15 Gy). Low doses were delivered to LM, LCx, and RCA (Dmean ≤ 1.3 Gy). The left ventricle (LV) was the most exposed cardiac chamber with Dmean/Dmax of 4.78 Gy/37 Gy. The strongest correlation with MHD was found for Dmean LAD (r = 0.81). For every 1 Gy increase in MHD, Dmean LAD rose by 3.4 Gy. However, the proportion of variance in Dmean LAD predictable from MHD was moderate (R² = 0.65). For all other cardiac substructures, R² values were < 0.7.ConclusionOur study showed high exposure of LAD and LV in LBCRT. With poor predictive value, MHD may underestimate doses to cardiac substructures. For optimal heart sparing radiotherapy, we recommend to consider LV and LAD as separate organ at risk.     

Empowering patients for radiation therapy safety: Results of the EMPATHY study

PurposeWith the increase of treatment complexity, enhancing safety is a key concern in radiation oncology. Beyond the involvement of the healthcare professional, patient involvement and empowerment could play a major role in that setting. We explored how patients perceived and fulfilled that role during their radiation treatment.Materials and methodsA voluntary and anonymous questionnaire was administered to all patients treated in our department between November 2013 and May 2014. The following data were collected: sociodemographic profile; information received and initiatives to search for additional information; behavior when an unusual treatment event was perceived; active involvement in the safety of the treatment; nature and perception of their own involvement. A statistical analysis was performed to assess behavioral predictors.ResultsA total of 155 patients answered the survey. Most of them were treated for prostate (n = 58, 37.4%), lung (n = 27, 17.4%), head and neck (n = 26, 16.8%) and breast (n = 25, 16.1%). Only eight patients (5%) had previously received radiation therapy. Ninety-five percent of the patients estimated they had received enough information about their treatment, but 48% would have wanted more. When patients noticed an unusual event during their treatment session, most of them (61%) reported it to the radiation therapist.ConclusionPatient participation to radiation therapy safety should be encouraged to ensure a cooperative risk management. Healthcare professionals need to inform the patients on the basic technical processes involved in their treatment. Patient empowerment should be added to the verifications made by the radiation therapists and physicians but should not replace them.     

Five-fraction HDR brachytherapy in locally advanced cervical cancer: A monocentric experience

PurposeThe 5-fraction scheme (5 × 5–5.5 Gy) is a common High-Dose Rate (HDR) intracavitary brachytherapy regimen for locally advanced cervical cancer (LACC). Yet, its equivalence with Pulse-Dose rate (PDR) schemes remains unproved. The present study aimed at reporting on the outcome of LACC patients treated with 5-fraction HDR brachytherapy.Materials and methodsThe medical records of all consecutive patients treated with curative-intent HDR brachytherapy for a LACC in a French Cancer Center were retrospectively reviewed.ResultsThirty-eight LACC patients underwent a 5-fraction intracavitary HDR brachytherapy between 2015 and 2019 (median dose = 25 Gy/5 fractions, following external-beam radiotherapy). Median age at diagnosis was 60 (range: 29–87). Thirty-one patients (81.5%) underwent concurrent chemotherapy. Tumor stages ranged from 3 IB2 (7.8%), 4 IB3 (10.5%), 4 IIA2 (10.5%), 12 IIB (31.7%), 1 IIIA (2.6%), 2 IIIB (5.3%), 7 IIIC1 (18.5%), 4 IIIC2 (10.5%), 1 IVA (2.6%) (2018 FIGO). Median D90% to CTV_HR reached 79.5 Gy (EQD2). Median D90% to CTV_IR reached 59.5 Gy (EQD2). Median Bladder D2cc was 69.8 Gy (EQD2). Median Rectum D2cc was 58.3 Gy (EQD2). Acute/late grade 3 toxicity was reported in one patient (2.6%). No grade 4–5 toxicity occurred. At a median 38 months follow-up, 10 patients (26.3%) had local (n = 7, 18.4%), nodal (n = 6, 15.7%) and/or distant (n = 7, 18.4%) relapse. Three-year overall survival rate was of 81.6%.ConclusionThe 5-fraction HDR scheme was well tolerated even in frail patients. Three-year local control was lower than expected. Treatment (absence of parametrial interstitial implants and use of cervical EBRT boost) and patients’ characteristics (age, comorbidities) may explain such results.     

Sarcomes d’Ewing localisés du rachis chez l’enfant : étude préliminaire d’escalade de dose comparant les techniques innovantes

PurposeAlthough radiosensitive, spinal locations of Ewing's sarcomas are challenging for the radiation oncologist due to poor radiation tolerance of the spinal cord. However, some favorable anatomical compartments – that may represent more than 20% – were associated with a better outcome and could benefit from a radiation dose escalation using the most recent radiation therapy techniques.Materials and methodsWe performed a dose escalation study on one patient, declined in two scenarios: (1) a tumour located within a single vertebral body and (2) a locally advanced disease involving the vertebral foramen and paraspinal soft tissues. Five dose-levels are proposed: 44.8 Gy, 54.4 Gy, 59.2 Gy, 65.6 Gy and 70.4 Gy (1.6 Gy per session, 8 Gy per week). The 3D-conformational technique is compared with static intensity modulated radiation therapy (IMRT), helical tomotherapy, volumetric modulated arc therapy (VMAT), stereotactic body robotic radiation therapy (SBRT) and protontherapy (passive scattering). Two constraints had to be respected in order to skip to the next level: the planned target volume (PTV) coverage must exceed 95% and the D_2% on the spinal cord shall not exceed a given constraint set at 50 Gy in case 1 and 44 Gy in case 2 due to initial neurological sufferance.ResultsOnly protontherapy, SBRT, helical tomotherapy and VMAT appear able to reach the last dose level while respecting the constraints in case 1. On the other hand, only helical tomotherapy seems capable of reaching 59.2 Gy on the PTV in case 2.ConclusionWith the most recent radiation therapy techniques, it becomes possible to deliver up to 70.4 Gy in a favorable compartment in this sham patient. Unfavorable compartments can receive up to 59.2 Gy. Definitive radiation therapy may be an interesting local treatment option to be validated in an early phase trial.     

Radionecrosis after repeated courses of radiotherapy under stereotactic conditions for brain metastases: Analysis of clinical and dosimetric data from a retrospective cohort of 184 patients

PurposeBetween 10 and 40% of patients with cancer will develop one or more brain metastases (BMs). Stereotactic radiotherapy (SRT) is part of the therapeutic arsenal for the treatment of de novo or recurrent BM. Its main interest is to delay whole brain radiation therapy (WBRT), which may cause cognitive toxicity. However, SRT is not exempt from long-term toxicity, and the most widely known SRT is radionecrosis (RN). The objective of this study was to analyze the occurrence of RN per BM and per patient.Material and methodsBetween 2010 and 2020, data from 184 patients treated for 915 BMs by two to six SRT sessions for local or distant brain recurrence without previous or intercurrent WBRT were retrospectively reviewed. RN was examined on trimestral follow-up MRI and potentially confirmed by surgery or nuclear medicine. For each BM and SRT session plan, summation V_12Gy, V_14Gy, V_21Gy and V_23Gy isodoses were collected. Volumes of intersections were created between the 12 Gy isodose at the first SRT and the 18 Gy isodose of the following SRT (V_18-12Gy).ResultsAt the end of follow-up, 23.0% of patients presented RN, and 6.3% of BM presented RN. Median follow-up of BM was 13.3 months (95%CI 18.3–20.8). The median interval between BM irradiation and RN was 8.7 months (95% CI 9.2–14.7). Six-, 12- and 24-month RN-free survival rates per BM were 75%, 54% and 29%, respectively. The median RN-free survival per patient was 15.3 months (95% CI 13.6–18.1). In multivariate analysis, the occurrence of RN per BM was statistically associated with local reirradiation (P < 0.001) and the number of SRTs (P < 0.001). In univariate analysis, the occurrence of RN per patient was statistically associated with the sum of all V_18-12Gy (P = 0.02). No statistical association was found in multivariate analysis. A sum of all V_{18-12 Gy} of less than 1.5 ml was associated with a 14.6% risk of RN, compared with 35.6% when the sum of all V_{18-12 Gy} was superior to 1.5 ml. The sum of all V_18-12Gy larger than 1.5 ml was associated with a 74% specificity and 53% sensitivity of RN (P < 0.001).ConclusionBased on these results, a small number of BMs show RN during repeated SRT for local or distant recurrent BMs. Local reirradiation was the most predictive factor of brain RN. A V_{18-12 Gy} larger than 7.6 ml in the case of local reirradiation or larger than 1.5 ml in proximity reirradiation were prognostic factors of RN. The more BM patients need radiation therapy, and the longer they survive after irradiation, the higher their individual risk of developing RN.     

Outcome of radiotherapy for invasive bladder cancer in older patients – not candidates for or decline cystectomy

PurposeRetrospective study to assess the role of radiotherapy (RT) in bladder cancer (BC) in patients who decline cystectomy or for whom it was contraindicated, regarding BC related events.Materials and MethodsA cross-sectional study, of patients with BC treated with RT, with or without chemotherapy was carried out, during the period March 2005 to March 2017, excluding patients who performed cystectomy. BC-related events were defined as haematuria, episodes requiring intravesical irrigations or transurethral resection or admission in Urology Department caused by symptoms related to BC.ResultsFifty-eight patients were included, 44 men and 14 women, whose median age at diagnosis was 78.3 years. Nine patients were treated with a RT dose below 50 Gy (20-45 Gy), in relation with non-resectable disease, nodal involvement, presence of metastasis or poor performance status. Forty-nine patients were treated with a RT dose above 50 Gy (maximum 60.4 Gy). The median follow-up time was 24 months, with BC-specific survival at 1/5 years of 87.5%/0.0% and 83.1%/33.9% in the group treated with RT dose below 50 Gy and above 50 Gy, respectively. Results revealed that the number of events decreased significantly after RT for both groups. For the two groups, the median of events before RT was 2.0, decreasing for 1.0 after RT (RT dose < 50 Gy: P = 0.011; RT dose ≥ 50 Gy: P = 0.026).ConclusionThis therapeutic approach can have an important role in older patients with bladder cancer, in terms of reducing disease related events. Symptom control was significantly achieved in both therapeutic groups.     

Intraoperative partial irradiation for highly selected patients with breast cancer: Results of the INTRAOBS prospective study

PurposeTo evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer.Methods and materialsInclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20 Gy/1 fraction): one dedicated electron linac (< October 2011), and afterwards a mobile linac (50 kV photons). The primary endpoint was the local recurrence rate (=ipsilateral breast cancer recurrences number). Secondary endpoints were recurrence-free survival (RFS), overall and specific survival, cosmetic results, and patient satisfaction.ResultsOf the present pre-planned analysis for the first 200 patients (median age: 68 years; range, 59–87 years) who received IORT between January 2010 and October 2014 (median follow-up of 53.4 months). A total of 193 patients were still alive. The local recurrence rate was 2.5% (n = 5). The 1- and 5-year local RFS rates were 100% and 95.2%, respectively. At 12 months post-surgery, satisfaction about IORT was excellent for 86.9% of patients. Cosmetic results were considered by patients and physicians as good or very good in 89.4% and 97.3% of cases, respectively.ConclusionsIORT for selected patients with breast cancer shows low recurrence rates, good cosmetic outcomes and excellent satisfaction.     

Fiducial marker implantation in prostate radiation therapy: Complication rates and technique

PurposeThis study aims to report the complication rate from the transrectal ultrasound-guided implantation of gold seed markers in prostate radiotherapy, as well as describing the technique used.Materials and methodsBetween May 2010 and December 2012, 169 patients with localized prostate cancer had an intraprostatic fiducial marker implantation under transrectal ultrasound guidance. The procedure included prophylactic antibiotic therapy, fleet enema, implantation performed by trained radiation oncologists at our center prior to image-guided radiotherapy. Toxicity occurring between implantation and subsequent radiotherapy start date was assessed. The following parameters were analyzed via medical chart review: antibiotic therapy, anticoagulant interruption, bleeding, pain, prostate volume, number of markers implanted, post-implantation complications and delay before starting radiotherapy.ResultsOf the 169 men, 119 (70.4%) underwent insertion of 4 fiducial markers and the other 50 (29.6%) had 3. The procedure was well-tolerated. There was no interruption of the implantation with regards to pain or hemorrhage. No grade 3 or 4 complications were observed. Seed migration rate was 0.32%, for the migration of 2 markers on 626 implanted. Mean prostate volume was 38 cm³ (range: 10–150 cm³). Two patients (1.18%) developed a urinary tract infection following the procedure: prostate volume of 25 and 65 cm³, four gold seed markers implanted, urinary tract infection resistant to prophylactic antibiotherapy, and treated with antibiotics specific to their infection as determined on urine culture.ConclusionTransrectal fiducial marker implantation for image-guided radiotherapy in prostate cancer is a well-tolerated procedure without major associated complications.     

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system

PurposeOver the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma.Material and methodsVarious patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis.ResultsA total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A = 15 patients, score 0–3); (B = 50 patients, score 4–7); (C = 33 patients, score 8–10); and (D = 13 patients, score 11–16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001).ConclusionThere exists a lack of universally acceptable ‘standard-of-care’ salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.