Giulia Riva

Radiotherapy in patients with cardiac implantable electronic devices: clinical and dosimetric aspects

As a result of aging, the number of patients with cardiac implantable electronic device (CIED) requiring radiotherapy (RT) continues to rise. The aim of this work was to evaluate RT-related malfunctions of CIED in a cohort of patients who underwent RT in our clinic from June 2010 to December 2016. We retrospectively analyzed 93 RT treatments in 63 patients with CIEDs. Patients were treated with 3D conformal RT, intensity-modulated RT and stereotactic RT. We collected clinical characteristics of cancer, models of CIEDs, total RT dose to tumor and radiation energy. Radiation dose delivered to CIED and its dysfunctions after RT was evaluated. Subgroup analysis of 48 RT treatments (32 patients) on chest and neck plus on 13 RT treatments (12 patients) with 18 MV neutron-producing photon energy considered as high risk was performed. The number of treatments of patients with CIEDs increased from 0.3% in 2011 to 1.2% in 2016. Two patients, treated with 18 MV photon beam, with implantable cardioverter–defibrillators (ICDs) that received a maximum dose of around 2.1xa0Gy, experienced adverse events: a reprogramming of ICD when the patient reached a delivered dose to the tumor of 32xa0Gy, and an altered sensing function requiring replacement after 11xa0months from the end of RT. Nearly 2% of patients with CIEDs from high-risk patients subgroup had experienced a damage of the device. Close cooperation between radiation oncologists, cardiologists, medical physicists and radiation technologists is needed to achieve the best practice management in these patients.

Cytoreductive prostate radiotherapy in oligometastatic prostate cancer: A single centre analysis of toxicity and clinical outcome

Objectives The current standard of care for patients with metastatic prostate cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to define the role of a local radiotherapy (RT) treatment in the mPCa setting. Methods We retrospectively reviewed data of patients with PCa and bone oligometastases at diagnosis treated in our institution with ADT followed by cytoreductive prostate-RT with or without RT on metastases. Biochemical and clinical failure (BF, CF), overall survival (OS) and RT-toxicity were assessed. Results We identified 22 patients treated with ADT and external-beam RT on primary between June 2008 and March 2016. All of them but four were also treated for bone metastases. RT on primary with moderately and extremely hypofractionated regimes started after 10.3 months (3.9–51.7) from ADT. After a median follow-up of 26.4 months (10.3–55.5), 20 patients are alive. Twelve patients showed BF after a median time of 23 months (14.5–104) and CF after a median of 23.6 months (15.3–106.1) from the start of ADT. Three patients became castration resistant, starting a new therapy; median time to castration resistance was 31.03 months (range: 29.9–31.5 months). According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC), only one patient developed acute grade 3 genitourinary toxicity. No late grade >2 adverse events were observed. Conclusion Prostate RT in oligometastatic patients is safe and offers long-lasting local control. When compared to ADT alone, RT on primary seems to improve biochemical control and long-term survival; however, this hypothesis should be investigated in prospective studies. Further research is warranted.

High-risk prostate cancer and radiotherapy: the past and the future. A benchmark for a new mixed beam radiotherapy approach

Micro‐Abstract Radiotherapy still remains a fundamental approach in the treatment of prostate cancer even in high‐risk patients. In the past decade, dose escalation has guaranteed a better local control of disease with a great tolerance in terms of side effects. Our results constitute a benchmarking exercise for a prospective trial that involves the use of heavy particles as integration of conventional treatment with photons. Background: The prognosis for patients with high‐risk prostate cancer is poor. No consensus exists on the most effective treatment. The aim of this retrospective study was to identify the biochemical progression‐free survival and the toxicity profile of patients with localized high‐risk prostate cancer treated with external beam radiation therapy. These results will constitute a benchmark for a prospective “mixed beam” trial: a boost with carbon ions followed by a pelvic photon intensity‐modulated radiotherapy (NCT02672449 [clinicaltrials.gov]). Patients and Methods: We retrospectively reviewed the data of 76 patients treated in our institution with photon radiation therapy according to the inclusion criteria of the future “mixed beam” trial: cT3a and/or serum prostate‐specific antigen > 20 ng/mL and/or Gleason score of 8 to 10, cN0 cM0. Toxicity, and biochemical and clinical progression‐free survival were assessed. Results: Seventy‐six patients fulfilled our criteria. The median follow‐up was 30.2 months (range, 7.2‐61.1). Biochemical progression was observed in 22 patients (28.9%) after a median time of 20.2 months (range, 5‐58.1) from the end of radiotherapy. Sixteen patients had clinical progression, in all the cases preceded by biochemical progression. Fifty‐seven patients (75%) are alive with no evidence of disease, 13 (17.1%) are alive with clinically evident disease, 6 died (3 of prostate disease 3.9%). Conclusion: Our results suggest that a more aggressive treatment is necessary. Local treatment intensification based on the “mixed beam” approach combining carbon ions (with its known radiobiological advantages) and photons might represent a promising strategy in high‐risk prostate cancer and it will be investigated with our prospective clinical trial.

A global Unified Dosimetry Index (gUDI) to evaluate simultaneous integrated boost radiotherapy plans in prostate cancer

PURPOSEnFormulation of a global Unified Dosimetry Index (gUDI) for the evaluation of prostate simultaneous integrated boost Volumetric Modulated Arc Therapy (VMAT by RapidArc) radiotherapy plans.nnnMETHODS AND MATERIALSnDose coverage, conformity, homogeneity and dose gradient index could be included in the Unified Dosimetry Index (UDI). We developed a global UDI to evaluate treatment plans containing volumes irradiated with different dose prescriptions: Intensity Modulated Radiation Therapy with simultaneous integrated boost (IMRT-SIB) with 2 dose levels (36.25u202fGy/5u202ffz for the whole prostate gland and 37.5u202fGy/5u202ffz for Dominant Intraprostatic Lesion (DIL)). To validate gUDI scoring system, 65 prostate cancer patients were evaluated. Mean (µ) and standard deviations (σ) were calculated for all dosimetry indices and gUDI. Furthermore, gUDI µ and σ were analyzed to compare and classify treatment plans: plans can be ranked as excellent, good, average or poor.nnnRESULTSnProstate Dose Gradient, Prostate Conformity and DIL Conformity indices had highlighted a major deviation from ideal scores. gUDI index classification showed most of the plans scored as average and good.nnnCONCLUSIONngUDI score can be a useful tool to quantify treatment plans quality also when volumes with different dose-prescription are treated.

Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation

PurposeTo evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT).Methods and materialsWe compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2xa0Gy/26 fractions) and 174 non-IGRT patients (80xa0Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed.ResultsMean follow-up was 81xa0months for hypo-IGRT and 90xa0months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS.ConclusionsA small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Cone-beam CT-based inter-fraction localization errors for tumors in the pelvic region

PURPOSEnTo evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed.nnnMETHODSnData of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3.nnnRESULTSnThe systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14u202fmm in the AP, 10u202fmm in the LL and 9-9.5u202fmm in the SI directions for the prostate and the gynecological groups and 9.5-10.5u202fmm in AP, 9u202fmm in LL and 8-10u202fmm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger.nnnCONCLUSIONSnwithout IGRT, large CTV-to-PTV margins up to 15u202fmm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.

“Give me five” ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35xa0Gy in 5 fractions, while 25 patients (13%) received 32.5xa0Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9–12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA)u2009>u20092xa0ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan–Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30u2009months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7xa0ng/ml (Pu2009=u20090.04), high- and intermediate-risk groups (Pu2009=u20090.002), low total dose (Pu2009=u20090.02) and Gleason score (GS) equal or greater than 7 (Pu2009=u20090.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (Pu2009=u20090.03) and risk groups (Pu2009=u20090.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients’ quality of life and potential overall health system and social benefits.

CyberKnife radiotherapy for orbital metastases: A single-center experience on 24 lesions

Objectives: To evaluate the feasibility, in terms of acute toxicity and symptom control, of CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CyberKnife-SRT) for metastatic orbital lesions. Methods: This retrospective study included patients with symptomatic metastases wholly located within the orbit. Palliative radiation treatment was performed using CyberKnife image-guided technology. Gross tumor volume was defined on a pre-radiotherapy magnetic resonance imaging. Acute and late toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale. Results: Between April 2012 and July 2016, 21 patients underwent CyberKnife-SRT for 24 orbital metastases from different primary tumors. Median treatment dose was 18u2009Gy (15–24u2009Gy) given in a median of 3 fractions (2–3 fractions) with a median dose of 6u2009Gy/fraction (5–10u2009Gy/fraction). Acute grade 1 toxicity was observed in eight cases. No local recurrence occurred after median follow-up of 6.2u2009months (1.1–30.0u2009months) among 16 lesions that underwent post-stereotactic radiotherapy magnetic resonance imaging. All patients reported decreasing pre-stereotactic radiotherapy symptoms without late toxicity. Follow-up >6u2009months (median 22.8u2009months) was available for nine lesions; complete and partial radiological response was registered in four and five of them, respectively. Conclusion: In our experience, CyberKnife-SRT is a well-tolerated treatment that offers high local and symptom control in patients with intraocular and periocular malignant lesions.

Short-term high precision radiotherapy for early prostate cancer with concomitant boost to the dominant lesion: ad interim analysis and preliminary results of Phase II trial AIRC-IG-13218

OBJECTIVEnTo report preliminary results of a cutting edge extreme hypofractionated treatment with concomitant boost to the dominant lesion for patients with early stage prostate cancer (PCa).nnnMETHODSnAIRC-IG-13218 is a prospective Phase II trial started in June 2015. Patients with low and intermediate risk PCa who met the inclusion criteria underwent extreme hypofractionated radiotherapy to the prostate (36.25u2009Gy in 5 fractions) and a simultaneous integrated boost to the dominant intraprostatic lesion (DIL) to 37.5u2009Gy. The DIL was identified by a multiparamentric MRI (mpMRI) co-registered with planning CT. Toxicity was assessed according to CTCAE v4.0 and RTOG/EORTC criteria. The preliminary evaluation of the first 13 patients was required to confirm the feasibility of the treatment before completing the enrollment of 65 patients.nnnRESULTSnThe first 13 patients completed the treatment between June 2015 and February 2016. With a median clinical follow-up of 17 months (range 11-26), no Grade 3 or 4 early toxicity was reported.nnnCONCLUSIONSnOur preliminary data about early toxicity of an extreme hypofractionated schedule with concomitant boost on the DIL are encouraging. The higher number of patients expected for the trial and a longer follow-up are needed to confirm these results. Advances in knowledge: The use of mpMRI to identify and boost the DIL is an innovative and interesting approach to PCa. Our preliminary findings suggest that dose escalation using DIL boost and extremely hypofractionated radiotherapy regimens might be a safe approach, allowing for short and effective treatment of organ-confined PCa.