Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups.

OBJECTIVE: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer. METHODS: A standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a 'per lesion' basis. The secondary end points were progression-free survival and overall survival, as well as toxicity. RESULTS: A total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10-60), in five fractions (range 1-10), with a median dose/fraction of 7 Gy (range 4-26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a 'per lesion' basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events. CONCLUSION: Our analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting.

Re-irradiation for recurrent high grade glioma (HGG) patients: Results of a single arm prospective phase 2 study.

BACKGROUND AND PURPOSE: Standard of care for recurrent high grade glioma (HGG) is missing. Several treatment options have been investigated including re-irradiation (re-RT). Results are promising but provided by retrospective studies. We designed a single arm prospective phase II study aiming to evaluate efficacy, and toxicity of re-irradiation. MATERIALS AND METHODS: Adults patients with good performance status, HGG diagnosis reclassified according to the new 2021 fifth edition WHO CNS classification, an interval time (IT) from previous RT ≥ 6 months were included. Outcome was evaluated by MRI imaging at 1 month, and every 3 months thereafter. Toxicities were evaluated in terms of radionecrosis occurrence, and neurocognitive status. RESULTS: Ninety recurrent HGG patients were treated, 11 oligodendroglioma grade 3, 18 astrocytoma grade 3 and 4, and 61 glioblastoma grade 4. The median age was 54 years, and majority had KPS 90-100. The median IT between first-RT and re-RT was 24 months. Re-surgery has been performed in 56.6%, and chemotherapy in 53.3%. The median follow up time was 64 months; median overall survival (OS) time,1,2,3-year OS rates were 17 months (95%CI 14-19), 66.7%±4.9, 32.6%±5.0, and 22.2 ± 4.7. Prognostic factors impacting on survival were age (p = 0.0154), IT between first RT and re-RT (p = 0.0051), glioma grade (p = 0.0090), and IDH status (p = 0.0001). Radionecrosis grade 2-3 occurred in 9 (10%) patients; neurocognitive functions remained stable until disease progression. CONCLUSION: Re-RT proved to be a safe and feasible treatment option with low toxicity. Younger patients with grade 3 IDH mutated gliomas, and a longer IT had the better outcome. TRIAL REGISTRATION NUMBER: NCT02567539.

Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

INTRODUCTION: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting. MATERIALS AND METHODS: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events. RESULTS: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively. CONCLUSION: V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.

Critical Re-Evaluation of a Failure Mode Effect Analysis in a Radiation Therapy Department After 10 Years.

PURPOSE: Failure mode effect analysis (FMEA) is a proactive methodology that allows one to analyze a process, regardless of whether an adverse event occurs. In our radiation therapy (RT) department, a first FMEA was performed in 2009. In this paper we critically re-evaluate the RT process after 10 years and present it in terms of a lesson learned. METHODS AND MATERIALS: A working group (WG), led by a qualified clinical risk engineer, which included radiation oncologists, physicists, a radiation therapist, and a nurse, evaluated the possible failure modes (FMs) of the RT process. For each FM, the estimated frequency of occurrence (O, range 1-4), the expected severity of the damage (S, range 1-5), and the detectability lack (D, range 1-4) were scored. A risk priority number (RPN) was obtained as RPN = OxSxD. The data were compared with the 2009 edition. RESULTS: In the 2020 analysis, 67 FMs were identified (27 in the 2009 series). The absolute risk values of the previous 3 highest FMs were generally reduced. The patient identification risk (highest value in the 2009 analysis) was reduced from 48.0 to 6.9, becoming the 51st RPN score, thanks to a patient barcode recognition within the bunker. The 2020 highest risk values regarded: (i-2020) the patient's inadequate recollection and reporting of his/her medical history (ie, anamnesis) during the first medical examination and (ii-2020) the incorrect interpretation of tumor and normal tissue in computed tomography images. The WG proposed corrective actions. CONCLUSIONS: In this single institution experience, the 10-year FMEA analysis showed a reduction in the previous higher RPN values thanks to the corrective actions taken. The new FMs and subsequent RPNs reveal the need for a continuous iterative improvement process.

A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups.

BACKGROUND: Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in non-small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC). MATERIALS AND METHODS: The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on "per-lesion" basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes. RESULTS: CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3 , lymph node disease, and biologically effective dose α/ß10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3-120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%. CONCLUSIONS: This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate. IMPLICATIONS FOR PRACTICE: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age <60 years, PTV <18 cm3 , lymph node disease, and biologically effective dose α/ß10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

Reirradiation of Locally Recurrent Prostate Cancer With Volumetric Modulated Arc Therapy.

PURPOSE: This study explores the efficacy and safety of reirradiation with modern radiation therapy techniques in patients previously irradiated for prostate cancer and affected by local relapse of disease. METHODS AND MATERIALS: Patients affected by previously irradiated prostate cancer were enrolled in this reirradiation study if they had a biochemical relapse and a 11C-choline positron emission tomography scan revealing the presence of a local recurrence of disease. Reirradiation consisted of a stereotactic treatment delivered by image guided radiation therapy-volumetric modulated arc therapy with flattening filter-free technology in 5 daily fractions. RESULTS: Twenty-three patients underwent reirradiation to the prostate, prostatic bed, or prostate and local recurrence. Re-treatment consisted of a median total dose of 25 Gy in 5 fractions. A biochemical response was observed in all cases. Acute toxicity was mainly genitourinary (GU) grade 1 to 2 (n = 13; 56.5%). One patient (4.3%) had grade 3 hematuria. A grade 1 GU late toxicity was registered in 4 patients (17.4%) and grade 3 in 1 patient (4.3%, urethral obstruction). Gastrointestinal toxicity was negligible. Regression analysis showed that only a short elapsed time in months from primary radiation therapy was significantly correlated with acute GU toxicity. After a median follow-up of 33 months (range, 5-58 months), the median biochemical recurrence-free survival was 19 months, and the 2-year biochemical recurrence-free survival (BRFS) was 41.7%. Median local control was 30 months; the 2-year local control rate was 58.1%. CONCLUSIONS: Reirradiation of patients with prostate cancer who underwent previous radiation therapy is a valuable option that can be safely considered to delay the beginning of hormonal treatment.

Predictive Factors for Response and Survival in a Cohort of Oligometastatic Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: This study evaluated patients, treatment, or disease characteristics that could predict response to stereotactic body radiation therapy (SBRT) and survival in a database of patients with oligometastatic disease from different solid tumors. METHODS AND MATERIALS: Patients treated with SBRT for oligometastatic disease between 2014 and 2015 were included. Patients were defined as oligometastatic if they were affected by a maximum of 5 active lesions in 3 different sites. They had to be treated with SBRT with radical intent. RESULTS: The study included 358 patients. With a median follow-up of 31.83 months, local control at 6 and 24 months was 94.6% and 78.9%, respectively. Distant progression was recorded in 279 patients (77.9%). Progression-free survival at 6 and 24 months was 66.1% and 18.4%, respectively. At last follow-up, 195 patients (54.5%) were still alive in 59 cases with no evidence of disease. The median overall survival (OS) was 34.7 months (95% confidence interval, 29.66-43.83). OS at 6 and 24 months was 96.07% and 63.57%, respectively. On multivariable analysis, the presence of lung metastases (hazard ratio [HR], 0.50 [0.33-0.75]; P = .001) and nodal metastases (HR, 0.44 [0.24-0.78]; P = .005) was related to longer OS. Primary lung cancer (HR, 1.89 [1.14-3.13]; P = .013), increasing age (HR, 1.02 [1.01-1.04]; P = .002), and the presence of metastatic sites other than the irradiated ones (HR, 2.19 [1.39-3.43]; P = .001) were all independent predictors of shorter OS. Local response was associated with OS. CONCLUSIONS: SBRT for patients with oligometastatic disease is effective. Local response is strongly correlated with patients'' prognosis, also underlying its relevance in a metastatic setting.

Role of Stereotactic Body Radiation Therapy for the Management of Oligometastatic Renal Cell Carcinoma.

PURPOSE: Kidney cancer has been increasing 1.7% annually. Renal cell carcinoma is the most common kidney cancer and it can metastasize. Our aim was to analyze patients treated with stereotactic body radiation therapy of renal cell carcinoma metastases. MATERIALS AND METHODS: A total of 58 patients (73 lesions) were treated from 2004 to 2016. Patients were candidates for analysis if a maximum of 3 metastases were diagnosed and the primary tumor was resected. Toxicity was classified according to Common Terminology Criteria for Adverse Events version 3. RESULTS: All patients had renal cell carcinoma, in particular the clear cell type in 82.7%. A total of 39 metastases (53.4%) were located in the lungs and 19 (26%) were in the lymph nodes. Less common were metastases to bone (9.5% of cases), the liver (4.1%) and the adrenal gland (6.8%). Median followup was 16.1 months (range 3.5 to 157.1). The local control rate at 12 and 18 months was 90.2% and 90.2%, respectively. The progression-free survival rate at 12 and 18 months was 46.2% (95% CI 32.2-59) and 35% (95% CI 21.4-48.9), respectively. On univariate and multivariable analyses metachronous and single metastases predicted better progression-free survival. Systemic therapy before stereotactic body radiation therapy predicted improved local control in clear cell cases. CONCLUSIONS: Stereotactic body radiation therapy can be considered a safe approach and it provides effective local control of oligometastatic renal cell carcinoma. However, future prospective studies are necessary to evaluate the impact on survival and quality of life.

Correction to: ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial.

Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.

ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with localized prostate cancer. Promising results in terms of disease control and toxicity have been reported with 4 to 5 SBRT fractions. However, question of how far can the number of fractions with SBRT be reduced is a challenging research matter. As already explored by some authors in the context of brachytherapy, monotherapy appears to be feasible with an acceptable toxicity profile and a promising outcome. The aim of this multicenter phase I/II prospective trialis to demonstrate early evidence of safety and efficacy of a single-fraction SBRT approach for the treatment of localized disease. METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone will be treated with a single SBRT fraction of 19 Gy to the whole prostate gland with urethra-sparing (17 Gy). Intrafractional motion will be monitored with intraprostatic electromagnetic transponders. The primary endpoint of the phase I part of the study will be safety as assessed by CTCAE 4.03 grading scale, while biochemical relapse-free survival will be the endpoint for the phase II. The secondary endpoints include acute and late toxicity, quality of life, progression-free survival, and prostate-cancer specific survival. DISCUSSION: This is the first multicenter phase I/II trial assessing the efficacy and safety of a single-dose SBRT treatment for patients with localized prostate cancer. If positive, results of ONE SHOT may help to design subsequent phase III trials exploring the role of SBRT monotherapy in the exclusive radiotherapy treatment of localized disease. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03294889 ; Registered 27 September 2017.

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.

Long-Term Follow-Up of Patients with Metastatic Epidural Spinal Cord Compression from Solid Tumors Submitted for Surgery Followed by Radiation Therapy.

OBJECTIVE: To evaluate the outcome of patients with epidural spinal cord compression from different solid tumors treated with a combined approach, surgery plus radiotherapy (RT), with a follow-up longer than 10 years. METHODS: Ninety-seven patients treated between 2002 and 2009 were included. Surgical treatment was performed in patients with good performance status, limited metastatic disease, life expectancy longer than 3 months, and progressive neurologic deficit and/or intractable pain. RT was performed delivering a median total dose of 30 Gy in 10 fractions. Clinical outcome was evaluated using the modified visual analog scale for pain, the Frankel scale for neurologic deficit, and magnetic resonance imaging before treatment, after treatment, and every 3 months thereafter. RESULTS: Palliative decompression was performed in 27% of patients, tumor curettage (debulking) was performed in 51%, and total vertebrectomy was performed in 22%, followed by RT in 78% of cases. Pain remission was obtained in 98% of patients, and recovery of neurologic function was obtained in 51%. The median follow-up time was 135 months (range, 96-209 months). The 5- and 10-year local control rates were 82.8% and 82.8%, respectively. The median and 5- and 10-year progression-free survival rates were 12 months, 16.9%, and 11.3%, respectively; the median and 5- and 10-year overall survival rates were 18 months, 21.3%, and 12%, respectively. On univariate and multivariate analysis, factors recorded as conditioning survival were the performance status and the presence of other metastases at the time of vertebral treatment (P < 0.01). CONCLUSIONS: Our update confirmed that surgery plus RT is a safe and feasible treatment with limited morbidity. In selected patients with favorable prognostic factors, the combined treatment may significantly impact on survival.

11C-Choline-Pet Guided Stereotactic Body Radiation Therapy for Lymph Node Metastases in Oligometastatic Prostate Cancer.

INTRODUCTION: aim is outcome of 11C-Choline-PET guided SBRT on lymph node metastases. MATERIALS AND METHODS: patients with 1 - 4 lymph node metastases detected by 11C-choline-PET were treated with SBRT. Toxicity, treated metastases control and Progression Free Survival were computed. RESULTS: twenty-six patients, 38 lymph node metastases were irradiated. No grade ≥ 2 toxicity. Median PSA-nadir after RT was 1.02 ng/mL. Post-treatment 11C-Choline-PET showed metabolic complete response in 17 metastases (44,7%), partial response in 9 metastases (38%). CONCLUSION: SBRT is effective and safe for lymph node metastases. PET is important in identification of gross tumor and evaluation of the response.

Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer.

BACKGROUND: Multidisciplinary management of oligometastatic breast cancer with local therapy could improve disease control. The aim of our study is the assessment of safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) in selected subset of patients. PATIENTS AND METHODS: Oligometastastic patients from breast cancer were treated with SBRT for 1-3 lung and liver lesions, in an observational study. Inclusion criteria were: age >18 years, ECOG 0-2, diagnosis of breast cancer, no extrapulmonary and/or extrahepatic disease, other metastatic sites stable or responding after chemotherapy were allowed, no life threatening conditions, less than 5 lung and liver lesions (with maximum diameter <5 cm), chemotherapy completed at least 3 weeks before treatment, written informed consent. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-point was local control (LC). Secondary end-points were toxicity, overall survival (OS) and progression-free survival (PFS). RESULTS: From April 2010 to June 2014, 33 patients for a total number of 43 lesions were irradiated. Median follow up was 24 months (range 3-59). Actuarial LC rates were 98% at 1 year and 90% at 2 and 3 years. Complete response, partial response and progressive disease were detected in 25 (53.2%), 16 (34%), and 6 (12.8%) lesions, respectively. Median OS was 48 months. Actuarial OS rates at 1 and 2 years were 93% and 66% respectively. Median PFS was 11 months, with a PFS rate at 1 and 2 years of 48% and 27%, respectively. At univariate analysis DFI >12 months, hormonal receptor positivity, medical therapies after SBRT showed a significant impact on OS. Treatment was well tolerated, with no G3-4 toxicities. CONCLUSIONS: SBRT is a safe and feasible alternative treatment of liver and lung oligometastases from breast cancer, in selected patients not amenable to surgery, with good local control and survival rate.

Cervical cancer response to neoadjuvant chemoradiotherapy: MRI assessment compared with surgery.

BACKGROUND: Imaging findings of residual cervical tumor after chemoradiotherapy can closely resemble those of post-irradiation inflammation. PURPOSE: To determine the diagnostic performance of magnetic resonance imaging (MRI) in evaluating residual disease after chemoradiotherapy in patients with locally advanced cervical carcinoma (LACC). MATERIAL AND METHODS: Retrospective analysis of prospectively collected data from 41 patients with histopathologically proven LACC (International Federation of Gynecology and Obstetrics stage ≥IB2) who underwent MRI before and after chemoradiotherapy. At each examination, a qualitative and semi-quantitative analysis of primary tumor, including tumor volume and signal intensity were assessed on T2-weighted (T2W) images. All patients had surgery after post-chemoradiotherapy MRI. MRI and histopathologic results were compared. RESULTS: All patients showed significant difference in tumor volume and signal intensity between pre- and post-chemoradiotherapy MRI (P < 0.0001). According to pathology, 27/41 (66%) patients had true negative and 2/41 (5%) had true positive post-chemoradiotherapy MRI. Eleven out of 41 (27%) patients showed inflammation with false positive post-chemoradiotherapy MRI and 1/41 (2%) had a false negative post-chemoradiotherapy MRI. Sensitivity, specificity, accuracy, positive predictive values, and negative predictive values of post-chemoradiotherapy MRI in predicting residual disease were 69%, 71%, 71%, 15%, and 96%, respectively. CONCLUSION: The differentiation of residual tumor from post-irradiation inflammation with early post- chemoradiotherapy MRI (within 28-60 days) is difficult with a high risk of false positive results. Combination of qualitative and semi-quantitative analysis does not improve the accuracy. Conversely, post-chemoradiotherapy MRI has a high negative predictive value with a low risk of false negative results. The role of conventional MRI combined with functional techniques should be evaluated.

Radiosurgery or Fractionated Stereotactic Radiotherapy plus Whole-brain Radioherapy in Brain Oligometastases: A Long-term Analysis.

AIM: To analyze the outcome of patients with brain oligometastases treated by radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) after whole-brain radiotherapy (WBRT). PATIENTS AND METHODS: Overall survival (OS) and local control (LC) were evaluated in patients (patients) with 1-2 brain metastases. RESULTS: Forty-seven patients were selected. They were submitted to WBRT (median dose=3,750 cGy) followed by SRS (17 patients; median dose=1,500 cGy) or FSRT (30 patients; median dose=2,000 cGy). Median follow-up was 102 months (range=17-151); the median survival was 22 months for the SRS group and 16 months for the FSRT group. One-year and 5-year survival was 56% and 16%, respectively, in SRT and 62.1% and 3%, respectively, in FSRT. Neither treatment proved to significantly impact OS (p=0.4). The 1-year LC rates were 80% and 61.1% in the two groups, respectively (p=0.15). CONCLUSION: SRS or FSRT after WBRT could offer the same outcomes in patients with brain oligometasteses. Further investigation is warranted to confirm these data and define the optimal stereotactic modality.

Adjuvant chemoradiotherapy in gastric cancer: a pooled analysis of the AIRO gastrointestinal group experience.

BACKGROUND: Given the poor compliance with adjuvant chemoradiotherapy (CRT) in gastric cancer reported in previous studies, a survey was conducted among 18 Italian institutions within the AIRO Gastrointestinal Group to investigate current treatment modalities, toxicities, and compliance with adjuvant CRT. PATIENTS AND METHODS: Data from 348 patients operated on for gastric cancer were collected retrospectively from September 2000 to June 2008 and analyzed. The adjuvant treatments included CRT according to center guidelines. In multivariate analysis, acute hematological, gastrointestinal, and renal toxicity (according to the RTOG Acute Radiation Morbidity Scoring Criteria) and compliance with treatment were studied, as well as risk factors for local control, metastasis-free survival, disease-free survival, and overall survival. RESULTS: Compliance with treatment was excellent: 95.7% of patients completed CRT. During CRT, acute G3-G4 ­hematological toxicity was 3.7% and acute G3-G4 gastrointestinal toxicity 4%. 78.4% of patients completed chemotherapy (CT), either before or after CRT. During CT acute G3-G4 hematological toxicity was 5.4% and acute G3-G4 gastrointestinal toxicity 6%. Overall, 74.1% of patients completed the prescribed treatment (CRT and CT). Doses greater than 4500 cGy did not compensate for more aggressive disease. The 5-year overall survival was 51%. CONCLUSIONS: The adjuvant treatment of gastric cancer within the AIRO group was diverse, but radiotherapy treatment was homogeneous (in terms of technique) and well tolerated. Toxicity was low and compliance with treatment was good during CRT; these results may be due to the radiotherapy technique applied. This survey could be used as a benchmark for further studies.

Stereotactic body radiation therapy for lung metastases from soft tissue sarcoma.

PURPOSE: To appraise the role of stereotactic body radiation therapy (SBRT) in patients with lung metastasis from primary soft tissue sarcoma. METHODS: Twenty-eight patients (51 lesions) were analysed. All patients were in good performance status (1-2 eastern cooperative oncology group (ECOG)), unsuitable for surgical resection, with controlled primary tumour and the number of lung metastases was ⩽4. In a risk adaptive scheme, the dose prescription was: 30Gy/1fr, 60Gy/3fr, 60Gy/8fr and 48Gy/4fr. Treatments were performed with Volumetric Modulated Arc Therapy. Clinical outcome was evaluated by thoracic and abdominal computed tomography (CT) scan before SBRT and than every 3months. Toxicity was evaluated with Common Terminology Criteria for Adverse Events (CTCAE) scale version 4.0. RESULTS: Leiomyosarcoma (36%) and synovial sarcoma (25%) were the most common histologies. Five patients (18%) initially presented with pulmonary metastasis, whereas 23 (82%) developed them at a median time of 51months (range 11-311months) from the initial diagnosis. The median follow-up time from initial diagnosis was 65months (5-139months) and from SBRT was 21months (2-80months). No severe toxicity (grades III-IV) was recorded and no patients required hospitalisation. The actuarial 5-years local control rate (from SBRT treatment) was 96%. Overall survival at 2 and 5years was 96.2% and 60.5%, respectively. At last follow-up 15 patients (54%) were alive. All other died because of distant progression. CONCLUSIONS: SBRT provides excellent local control of pulmonary metastasis from soft tissue sarcoma (STS) and may improve survival in selected patients. SBRT should be considered for all patients with pulmonary metastasis (PM) and evaluated in a multidisciplinary team.

Primary systemic treatment and concomitant low dose radiotherapy for breast cancer: final results of a prospective phase II study.

BACKGROUND: To evaluate the efficacy of preoperative low dose fractionated radiotherapy (LD-FRT) and chemotherapy in breast cancer. MATERIALS AND METHODS: Patients with stage IIA-IIIA breast cancer, received LD-FRT (0.40 Gy bid, on day 1 and 2, for 6 cycles) to primary tumor volume and concurrent chemotherapy with non-pegylated liposomal anthracycline and docetaxel. Pathological response was assessed by Mandard Tumor Regression Grade (TRG). We evaluated the pathological major response rate (PMRR) as TRG1 and TRG2. The expected outcome was a PMRR of 60%. The accrual was determined by the single proportion powered analysis (α = 0.05, power = 0.8). RESULTS: Twentyone patients were enrolled. No grade 2-4 acute skin and hematological toxicity was observed. TRG1 was obtained in 3 patients (14.3%), TRG2 in 4 patients (19%). The PMRR was 33.3%; it does not concur with the expected result, but is similar to that of chemotherapy alone. According to molecular subtype, 2/11 luminal A patients and 4/6 luminal B patients obtained a PMRR to preoperative treatment (35.3%); 1/4 basal like patients reported TRG1 (25%). CONCLUSIONS: LD-FRT concomitant with primary systemic treatment has a good toxicity profile. The response rate is consistent with that of chemotherapy alone, and suggests different interactions between low dose radiotherapy and molecular subtypes. Additional investigations are planned.

Chemoradiation and brachytherapy in extrahepatic bile duct carcinoma.

BACKGROUND: To explore the role of radiotherapy in the extrahepatic bile duct carcinoma, and to understand if and when radiotherapy could be effective for this group of patients. METHODS: A systematic review of recently published literature was completed. Recent studies using radiotherapy with survival data, resection rates and quality of life data have been analyzed. RESULTS: There are no randomized trials regarding the treatment of extrahepatic cholangiocarcinoma. The bulk of available studies suggest that in some cases radio-chemotherapy can be used as adjuvant therapy. Radiotherapy could also have a role in unresectable cholangiocarcinoma: external radiotherapy or intraluminal brachytherapy--alone or in combination--could improve the outcome in selected patients. Finally, radiotherapy, and in particular intraluminal brachytherapy, could be used as a palliative treatment to improve the quality of life and in controlling symptoms. CONCLUSION: The role of radiotherapy in extrahepatic cholangiocarcinoma remains undefined due to the lack of randomized trials or otherwise properly controlled studies.