PROACTA: a survey on the actual attitude of the Italian radiation oncologists in the management and prescription of hormonal therapy in prostate cancer patients.

AIM: To investigate the actual attitude of Radiation Oncologists in the prescription of hormonal therapy in prostate cancer (PC) with or without Radiation Therapy (RT). MATERIALS AND METHODS: In 2019, a survey named Prescription of Radiation Oncologists ACtual Attitude including 18 items was sent to all Italian Radiation Oncologists of the Italian Association of Radiotherapy and Clinical Oncology. The first 4 items were about the Radiation Oncology Centers characteristics and years of practice of the respondents. The remaining 14 items concerned the setting in which hormone therapy was prescribed in PC patients (radical, postprostatectomy/oligometastatic state), the kind of drug, the choice modality (Multidisciplinary Group/autonomy decision) and other factors. RESULTS: A total of 127 questionnaires were returned, mainly by Northern Italy Radiation Oncology Centres (44.9%), and by experienced Radiation Oncologists (78%), who declared to prescribe independently hormone therapy in 85.8% of cases. The Androgen deprivation therapy (ADT) prescription in castration naive PC was made independently by 56.7% of respondents and associated with radical RT, postoperative or salvage RT according to various risk factors. In castration-sensitive oligorecurrent PC, the majority (51.2%) administered ADT only if local ablative treatment was not feasible, while in metastatic castration resistant disease novel hormone therapy use was established in almost half of cases within multidisciplinary board. Radiation Oncologists could prescribe these drugs independently in 64% of cases. CONCLUSION: Our survey established the prescription attitude of ADT and new hormonal agents (abiraterone, enzalutamide, apalutamide) by Italian Radiation Oncologists and highlighted the importance of expertise in global PC management.

Non-palliative radiotherapy in ab initio oligometastatic prostate cancer: an Italian national survey.

AIMS: The purpose of this survey was to investigate the current opinion among Italian radiation oncologists regarding the non-palliative radiotherapy in ab initio oligometastatic prostate cancer (OMPC) patients. METHODS: A link to complete the survey was sent via e-mail to Italian radiation oncologists on February 2018. It was requested that only one physician per facility completed the survey, and that he/she was dedicated to PC management in his/her daily clinical practice. The questionnaire consisted of 15 questions concerning the management of OMPC. RESULTS: One hundred and eleven radiation oncologists filled in the questionnaire. The majority of them see ≤ 10 patients affected by OMPC in a year. More than 80% of respondents would perform radiotherapy (RT) to both the prostate and all metastases sites, but mostly up to 2-3 metastases; furthermore, > 80% of physicians would perform RT on both nodal and bone secondary lesions. Most respondents deem a choline- or prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) mandatory before considering a patient affected by OMPC for non-palliative RT. The association of RT with androgen deprivation therapy for at least 12 months would be recommended by > 50% of respondents. In the follow-up phase, the majority would suggest a clinical examination and PSA every 3-6 months and a choline- or PSMA-PET only at biochemical progression. More than 90% of respondents confirmed to be interested in participating in a multicentre study regarding this subject. CONCLUSIONS: This survey investigated the current opinion of Italian radiation oncologists and confirmed their interest in OMPC management.

Intensity-modulated radiotherapy and hypofractionated volumetric modulated arc therapy for elderly patients with breast cancer: comparison of acute and late toxicities.

PURPOSE: To evaluate the differences between conventional fractionated intensity-modulated radiotherapy (IMRT) and hypofractionated (HypoRT) volumetric modulated arc therapy (VMAT) in elderly women affected by early-stage breast cancer (BC) in terms of RT-related acute/late side effect. MATERIALS AND METHODS: Between October 2011 and July 2015, 80 consecutive elderly BC patients were treated with IMRT for 5 weeks (40 patients) or HypoRT-VMAT for 3 weeks (40 patients). Inclusion criteria were: age ≥ 70 years, early BC (pT1-2 pN0-1), no prior neoadjuvant chemotherapy and non-metastatic disease. For patients receiving IMRT or HypoRT-VMAT, a total dose of 50 Gy (25 fractions) or 40.5 Gy (15 fractions) was prescribed to the whole ipsilateral breast, respectively. All patients received a simultaneously integrated boost up to a total dose of 60 Gy for IMRT and 48 Gy for HypoRT-VMAT. Acute and late side effects were evaluated using the RTOG/EORTC radiation morbidity scoring system. RESULTS: With a median follow-up of 45 months, acute skin toxicity was overall very low, with grade 1 in 25 cases (62.5%) of the IMRT group and 21 cases (52.5%) of the HypoRT-VMAT group, while grade 2 toxicity was reported in 10 IMRT patients (25%) and 1 HypoRT-VMAT patient (2.5%) (p = 0.001). Regarding late adverse events, only grade 1 skin toxicity was recorded. CONCLUSION: The present study showed that whole breast IMRT and HypoRT-VMAT are feasible and well tolerated in early-stage BC elderly patients and that HypoRT-VMAT is affected by lower risk of acute and late RT-related side effects.

Linac-based stereotactic body radiation therapy for unresectable locally advanced pancreatic cancer: risk-adapted dose prescription and image-guided delivery.

BACKGROUND: Stereotactic body radiation therapy (SBRT) represents a new treatment option for locally advanced pancreatic cancer (LAPC). An accurate treatment planning with risk-adapted dose prescription with adherence to specific dose constraints for organs at risk (OARs) and the use of daily cone beam CT (CBCT) for image guidance could allow an effective and safe treatment delivery. Here, feasibility and efficacy of SBRT in LAPC treated in our cancer care center are reported. PATIENTS AND METHODS: 33 unresectable LAPC patients underwent SBRT. In order to respect OAR dose constraints, a risk-adapted dose prescription strategy was adopted, choosing between the following schedules: 42 Gy or 45 Gy in 6 daily fractions with a biologically effective dose (BED) > 70 Gy10 or 36 Gy/6 fractions (estimating a BED 57.6 Gy10). SBRT was delivered with volumetric modulated arc technique (VMAT) and flattening filter-free (FFF) mode. Image guidance was performed by means of CBCT before every treatment session. The patients were evaluated at the end of treatment for acute toxicity and at 3, 6, and 12 months for late toxicity and treatment response. RESULTS: At the time of analysis, the median follow-up was 18 months (range 5-34 months). Prior to SBRT, 24 out of 33 patients received induction chemotherapy. Although all patients were previously judged as unresectable, 6 out of 33 (18%) underwent surgery after SBRT; all of them received a BED > 70 Gy10. One-year LC and OS were 81% and 75%, respectively. A total of 12 patients (37%) had an extra-pancreatic progression. No cases of ≥G3 acute or late toxicity were reported. CONCLUSION: In our experience, risk-adapted dose prescription and image-guided SBRT represents an effective treatment option for LAPC patients.

Comorbidities and intensity-modulated radiotherapy with simultaneous integrated boost in elderly breast cancer patients.

PURPOSE: To evaluate the impact of comorbidity assessment on compliance to intensity modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in elderly patients affected by early stage breast cancer (BC). MATERIALS AND METHODS: 40 consecutive patients were treated with SIB-IMRT (50 Gy in 25 fractions to the whole breast, and simultaneously 60 Gy to the surgical bed) for invasive BC after conserving surgery. Inclusion criteria were: age ≥ 70 years, pT1-2 disease, pN0-1, no neoadjuvant chemotherapy, non-metastatic disease. Charlson comorbidity index was used for comorbidity evaluation. RESULTS: Median follow-up was 44 months. At the time of the analysis, OS and LC rates were 100%. All patients completed the SIB-IMRT without interruptions. Acute skin toxicity was recorded as follows: grade 0 in 5 patients (12.5%), grade 1 in 25 cases (62.5%), and grade 2 in 10 patients (25%). Regarding late adverse events, skin toxicity was registered as follows: grade 0 in 27 patients (67.5%) and grade 1 in 13 cases (32.5%). No toxicity ≥grade 2 was registered. At statistical analysis, the presence of comorbidities and the breast volume >700 cc were related to skin grade 2 acute toxicity (p = 0.01, p = 0.04). In terms of cosmetic results, 98 and 2% of patients considered the result as good/excellent and as fair after RT, respectively. No patients had a poor cosmetic outcome. CONCLUSION: The present study showed the feasibility of SIB-IMRT in early stage BC elderly patients and that the absence of comorbidity reduced the risk of acute radiation toxicity.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

AIM: To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). MATERIALS AND METHODS: 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT. RESULTS: Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). CONCLUSIONS: Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

GUROPA survey: genito-urinary radiation oncology prescription attitudes.

AIMS: To investigate the role of Radiation Oncology in the management of genito-urinary (GU) cancer excluding prostate and penile cancer. METHODS: The questionnaire was focused on the evaluation of the degree of involvement of radiation oncologists in the work-up of bladder, renal cell carcinoma and testicular cancer (TC). RESULTS: Eighty-eight radiation oncologists completed the survey. The majority (85.4%) of participating radiation oncologists were senior consultants (> 5 years of experience). Sixty-four (73.6%) carried out a multidisciplinary tumor board discussion of GU cases, while 23 (26.4%) did not. Seventy-five percent of responders reported that, every year, visited < 50 GU patients (pts), 18.1% visited 50-100 pts and 6.9% visited > 100 pts. Bladder cancer, curative radiotherapy (RT) as part of trimodality approach was claimed to be adopted in less than 10 cases per year. Regarding renal cell carcinoma (RCC) patients, primary tumor directed RT was adopted only in 8 cases (9.4%) in at least 10 pts per year. Palliative RT was more frequent in RCC (48.2%) in over than 10 pts per year. In case of TC, the prescription of RT was limited (< 10 patients per year) due to the low incidence of disease and recent shift to surveillance as a first option in stage I seminoma. CONCLUSIONS: Our survey showed that radiation oncologists are rarely involved in the decision making strategy of GU cancer, despite many clinical trials support RT use. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.

Radiotherapy in patients with HIV: current issues and review of the literature.

Although the introduction of highly active antiretroviral therapy has radically improved the life expectancy of patients with HIV, HIV positivity is still considered a major barrier to oncological treatment for patients with cancer because of their worse prognosis and increased susceptibility to toxic effects compared with patients who are immunocompetent. The use of radiotherapy with or without chemotherapy, immunotherapy, or molecular targeted therapy is the standard of care for several cancers. These new drugs and substantial improvements in radiotherapy techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and stereotactic ablative radiotherapy, are optimising the feasibility of such anticancer treatments and are providing new opportunities for patients with cancer and HIV. In this Review, we discuss the role of radiotherapy, with or without chemotherapy or new drugs, in the treatment of cancer in patients with HIV, with a focus on the efficacy and tolerability of this approach on the basis of available evidence. Moreover, we analyse and discuss the biological basis of interactions between HIV and radiotherapy, evidence from preclinical studies, and immunomodulation by radiotherapy in the HIV setting.

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study.

BACKGROUND: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC). METHODS: Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1-3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients. RESULTS: About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design. CONCLUSIONS: Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

18F-Fluorodeoxyglucose-PET/CT in locally advanced head and neck cancer can influence the stage migration and nodal radiation treatment volumes.

AIM: To analyze the impact of 18F-fluorodeoxyglucose-PET/CT (PET/CT) in the radiotherapy (RT) planning strategy in HNC, correlating CT-scan and PET/CT performances. MATERIALS AND METHODS: Inclusion criteria were: age >18 years old, histologically proven head and neck cancer (HNC), patients candidate to definitive RT ± chemotherapy, stage of disease by means of PET/TC and CT-scan performed at our Cancer Care Center. RESULTS: Sixty patients were analyzed. The following primary tumor sites were investigated: nasopharynx (13%), oropharynx (42%), oral cavity (32%) and larynx non-glottic (13%). Globally, PET/CT findings caused changes on nodal radiation treatment volumes in 10% of all the population of study. Specifically, in 5 cases out of 19 oral cavity tumors (26%), PET/CT detected neck-nodes positive (not detected at CT-scan). These findings have allowed to change the patients management, including PET/CT neck-nodes positive in the high-risk RT volumes. CONCLUSION: In the RT planning strategy, the present findings support the use of PET/CT to improve upfront regional staging of HNC disease, particularly for oral cavity tumors. Further investigations are advocated to evaluate if this strategy could impact on long-term outcomes in terms of local control and overall survival.

Synchronous bilateral breast cancer irradiation: clinical and dosimetrical issues using volumetric modulated arc therapy and simultaneous integrated boost.

OBJECTIVES: The aim of the present retrospective analysis was to evaluate dosimetric parameters, feasibility and outcome for Synchronous Bilateral Breast Cancer (SBBC) patients treated with adjuvant radiotherapy (RT) by Volumetric Modulated Arc Therapy (VMAT). METHODS: From September 2011 to April 2016, 1100 Breast Cancer (BC) patients were referred to our institution to receive adjuvant breast RT, and those with SBBC were selected for the present analysis. A total of 16 patients were identified. A total dose of 50 Gy in 25 fractions was prescribed to the Planning Target Volume of the whole bilateral breast (PTVBN) with or without the supraclavicular and infraclavicular nodes, while a total dose of 60 Gy in 25 fractions was prescribed to the surgical bed (PTVboost). Several V xGy and Dx% parameters were analyzed for the PTVs, together with Conformity and Homogeneity indexes (CI, HI), and for the critical Organs at risk (OARs), lungs and heart first. RESULTS: With a median follow-up of 24 months, no acute or late side effects more than grade 2 were observed. All patients are alive without any sign of disease. For target dose coverage, our observed inter-patients averages (±1 sd) were V 95% Dp = 96.7 ± 1.6% (96.3 ± 1.8%) to the left (right) PTVBN, V 95% Dp = 98.6 ± 2.7% (99.4 ± 0.9%) to the left (right) PTVboost, and D 2% = 64.4 ± 1.8 Gy (65.0 ± 2.0 Gy) to the left (right) PTVboost, respectively. With regard to the heart, the inter-patient average of D mean was 8.3 ± 3.3 Gy. For the lungs, the inter-patient average of D mean, V 5 Gy and V 20 Gy were 11.8 ± 2.3 Gy, 78.9 ± 15.3% and 15.7 ± 5%, respectively. CONCLUSIONS: The present retrospective analysis showed the feasibility, tolerability and safety of VMAT in the treatment of SBBC patients. Further studies are necessary to confirm these preliminary data.

Stereotactic ablative radiation therapy for brain metastases with volumetric modulated arc therapy and flattening filter free delivery: feasibility and early clinical results.

AIM: For selected patients with brain metastases (BMs), the role of stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) is well recognized. The recent introduction of flattening filter free (FFF) delivery during linac-based SRS or SFRT allows shorter beam-on-time, improving patients' comfort and facility workflow. Nevertheless, limited experiences evaluated the impact of FFF linac-based SRS and SFRT in BMs treatment. Aim of the current study was to analyze SRS/SFRT linac-based FFF delivery for BMs in terms of dosimetric and early clinical results. MATERIALS AND METHODS: Patients with life expectancy >3 months, number of BMs <5, diameter <3 cm, and controlled or synchronous primary tumor received SRS/SFRT. The prescribed total dose and fractionation, based on BMs size and proximity to organs at risk, ranged from 15 Gy in 1 fraction to 30 Gy in 5 fractions. A FFF volumetric modulated arc therapy (VMAT) plan was generated with one or two coplanar partial arcs. Toxicity was assessed according to CTCAE v4.0. RESULTS: From April 2014 to February 2016, 45 patients (89 BMs) were treated with SRS/SFRT linac-based FFF delivery. The mean beam-on-time was 140 s for each lesion (range 90-290 s) and the average brain Dmean was 1 Gy (range 0.1-4.8 Gy). At the time of analysis, local control was reported in 93.2% (83/89 BMs). With a median follow-up time of 12 months (range 1-27 months), the median overall survival was 14 months and the 6-month overall survival was 77%. Finally, the median intracranial disease control was 11 months. Acute and late toxicities were acceptable without severe events (no adverse events ≥G2 were recorded). CONCLUSIONS: These preliminary results highlighted the feasibility and safety of linac-based SRS/SFRT with FFF mode for BMs patients. A longer follow-up is necessary to confirm the efficacy of this treatment modality in BM patients.

Three-dimensional conformal versus intensity modulated radiotherapy in breast cancer treatment: is necessary a medical reversal?

OBJECTIVES: Aim of the present study is to compare three-dimensional conformal RT (3D-CRT) and 4-fields intensity modulated radiation therapy (4f-IMRT) treatment plans, in terms of target dose coverage, integral dose and dose to Organs at risk (OARs) in early breast cancer (BC). METHODS: Twenty consecutive BC patients, after lumpectomy, were selected for the present analysis. A total dose of 50 Gy and a simultaneous dose of 60 Gy in 25 fractions was prescribed to Planning Target Volume of the whole breast (PTVbreast) and of the surgical bed, respectively. For each patient, a 3D-CRT plan and a sliding-window 4f-IMRT plan were generated. Conformity and homogeneity indexes (CI, HI) and various organ specific VxGy values were analyzed for PTVs, OARs and normal tissue (NT), respectively. RESULTS: In terms of HI, 4f-IMRT was superior to 3D-CRT for the PTVbreast (p < 0.0001), and a significant difference for CI was observed in favor of 4f-IMRT (p < 0.0001).In terms of dose to OARs, a superiority of 4f-IMRT was shown. For NT, all parameters are in favor of IMRT, except the V 5Gy for which the difference was not statistically significant. The average NT-Dmean was 2.7 ± 0.7 for 3D-CRT and 1.8 ± 0.5 for 4f-IMRT (p < 0.0001). CONCLUSIONS: 4f-IMRT technique significantly reduced the dose to OARs and NT, with a better target coverage compared to 3D-CRT.

Radiotherapy in patients with connective tissue diseases.

The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy.

Whole brain radiotherapy with hippocampal avoidance and simultaneous integrated boost for brain metastases: a dosimetric volumetric-modulated arc therapy study.

OBJECTIVE: To develop a feasible volumetric modulated arc therapy (VMAT) treatment in whole brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) and hippocampal (HP) sparing in 1-5 brain metastases (BMs). METHODS AND MATERIALS: Ten patients with 20 BMs received a WBRT prescription of 20 Gy, SIB dose on BMs of 40 Gy/5 fractions. PTVWBRT was generated from brain minus BMs-PTVs (PTVSIB) and planning organ at risk volume to HP. All plans were evaluated in: homogeneity index (HI), target coverage (TC), maximum dose to prescription dose ratio (MDPD), prescription isodose to target volume ratio (PITV) and paddick conformity index (CI). We also evaluate D100%, mean and maximum doses to HP. Planning objectives were for PTVWBRT, D2% = 25 Gy with acceptable deviation of 26.7 Gy and D98% ≥ 16.7 Gy; for PTVSIB D95% ≥ 38 Gy; for HP, D100% = 6 Gy with acceptable deviation of 6.7 Gy, Dmax = 10.7 Gy with acceptable deviation of 11.3 Gy, a mean dose of 8 Gy. RESULTS: Mean number of BMs was 2 (range 1-5). Mean values for BMs were volume of PTVSIB = 5.1 ± 4.9 cc, dose to 95% of PTVSIB 39.3 ± 0.9 Gy, HI 0.083 ± 0.03, TC 0.96 ± 0.24, CI 0.78 ± 0.17. Mean MDPD was 1.06 ± 0.02 and PITV 0.96 ± 0.24. For WBRT, mean target volume was (13.46 ± 2)*10(2) cc, mean dose to 90% of PTVWBRT 19.8 ± 0.2 Gy, mean HI 0.42 ± 0.12 and TC 0.78 ± 0.11. Mean and maximum HP doses were 7.7 ± 0.3 Gy and 10.5 ± 0.5 Gy. Mean dose to 100% of HP volume (D100%) was 6.7 ± 0.3 Gy. CONCLUSIONS: WBRT plus SIB with HP avoidance with VMAT was feasible. All dosimetric parameters were satisfied for PTVWBRT and PTVSIB.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Treatment of muscle-invasive bladder cancer in patients without comorbidities and fit for surgery: Trimodality therapy vs radical cystectomy. Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIM: To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC). MATERIAL AND METHODS: Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made. RESULTS: Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72-77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC. CONCLUSIONS: TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery.