Definitive results of a prospective non-randomized phase 2 study on stereotactic body radiation therapy (sbrt) for medically inoperable lung and liver oligometastases from breast cancer.

BACKGROUND AND PURPOSE: To report mature results for local control and survival in oligometastatic (OM) breast cancer patients treated with stereotactic body radiotherapy (SBRT) on lung and/or liver lesions in a phase II trial. METHODS: This is a prospective non-randomized phase II trial (NCT02581670) which enrolled patients from 2015 to 2021. Eligibility criteria included: age > 18 years, ECOG 0-2, diagnosis of breast cancer, maximum of 4 lung/liver lesions (with a maximum diameter < 5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. The primary end-points were local control (LC) and treatment-related toxicities. The secondary end-points included overall survival (OS), distant metastasis-free survival (DMFS), time to next systemic therapy (TTNS), poly-progression free survival (PPFS). RESULTS: The study included 64 patients with a total of 90 lesions treated with SBRT. LC at 1 and 2 years was 94.9 %, 91 % at 3 years. Median local control was not reached. Median OS was 16.5 months, OS at 1, 2 and 3 years was 87.5 %, 60.9 % and 51.9 %, respectively. Median DMFS was 8.3 months, DMFS at 1, 2 and 3 years was 38.1 %, 20.6 % and 16 % respectively. At univariate analysis, local response to SBRT was found to be statistically linked with better OS, DMFS and STFS. CONCLUSION: SBRT is a safe and valid option in oligometastatic breast cancer patients, with very high rates of local control. An optimal selection of patients is likely needed to improve survival outcomes and reduce the rate of distant progression.

Oligometastatic Prostate Cancer Treated with Stereotactic Body Radiation Therapy: The Role of Three-Dimensional Tumour Volume in Patient Survival.

AIMS: The definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. MATERIALS AND METHODS: This monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan-Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. RESULTS: Between 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4-93.4), 74.9% (95% confidence interval 66.1-81.7) and 57.2% (95% confidence interval 45.8-67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06-3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01-3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34-4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4-70.9), 31.5% (95% confidence interval 22.8-40.6) and 24.7% (95% confidence interval 16.0-34.3). CONCLUSIONS: This study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome.

Risk-group Classification by Recursive Partitioning Analysis of Patients Affected by Oligometastatic Renal Cancer Treated with Stereotactic Radiotherapy.

AIMS: Due to the absence of consensus on metastases-directed treatment in kidney cancer, we conducted an analysis of patients treated with stereotactic radiotherapy (SRT) on cranial or extracranial metastases to classify them in survival class risk according to pre-treatment characteristics. MATERIALS AND METHODS: We included oligometastatic kidney cancer patients treated with SRT on up to five metastases. Concomitant systemic treatment was allowed. End points included overall survival and the binary classification tree approach with recursive partitioning analysis was applied to stratify patients into overall survival risk groups. RESULTS: In total, 129 patients were treated on 242 metastases. The brain was the most common site (34.71%), followed by lung (25.62%). With a median follow-up of 19.4 months, 1- and 3-year overall survival were 82.62 and 55.11%. The recursive partitioning analysis identified four prognostic classes. Class 1 included patients aged ≤ 65 years treated on extracranial metastases, with 3-year overall survival of 82.66%. Class 2 included patients aged > 65 years, without history of metastatic bone disease, treated on extracranial metastases, with a 3-year overall survival of 67.91%. Patients aged > 65 years and a history of bone disease, treated on extracranial metastases, were classified as class 3, with a 3-year overall survival of 37.50%. Class 4 included patients treated on brain metastases, with a 3-year overall survival of 9.70%. CONCLUSION: We produced a stratification model that can predict survival of oligometastatic kidney cancer patients treated with metastases-directed SRT. Site of disease, patient's age and presence of bone disease can help clinicians in the decision-making process.

Long term results of a phase II trial of hypofractionated adjuvant radiotherapy for early-stage breast cancer with volumetric modulated arc therapy and simultaneous integrated boost.

PURPOSE: to report toxicity and cosmetic outcome with a median follow-up of 6 years of a phase II trial of hypofractionated radiotherapy with volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) for early-stage breast cancer after conservative surgery. MATERIALS AND METHODS: From August 2010 to September 2014, patients requiring adjuvant radiotherapy for early-stage breast cancer were treated according to a phase I-II protocol with SIB to 40.5 and 48 Gy to the breast and the boost region, respectively, with VMAT technique. The primary endpoint evaluated the treatment feasibility regarding adherence to required dose constraints for target, heart and lungs. Acute and late toxicity, local and distant control were secondary endpoints. RESULTS: 450 patients were included in the trial and analysed after a median follow-up of 6 years. Acute toxicity was already presented in a previous paper. Regarding late toxicity, 93% of patients had no skin alteration at five years, while 5.3% and 1.3% did record G1 and G2 residual toxicity, respectively. Cosmetic outcome was scored good or excellent in almost all cases (97.2%), fair only in 2.3% of patients. Residual tenderness in the irradiated breast was reported by 10% of patients. Cosmesis and breast pain improved during follow-up. Two cases of G2 pneumonitis and two cases of ischemic cardiopathy were registered during follow-up. Five cases presented local recurrence in the homolateral breast, four patients had a new primary cancer in the contralateral breast, while distant metastasis developed in 7 patients. CONCLUSION: After more than six years, hypofractionated VMAT with SIB for adjuvant radiotherapy in early-stage breast cancer patients remains a safe and effective approach. Mature data on skin toxicity and cosmetic outcome are encouraging. However, longer follow-up is required to evaluate local control, cardiac toxicity and secondary carcinogenesis.

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PURPOSE: The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. METHODS: A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. RESULTS: With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. CONCLUSION: HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

Radical hypo-fractionated radiotherapy with volumetric modulated arc therapy in lung cancer : A retrospective study of elderly patients with stage III disease.

BACKGROUND: This study aimed to analyse the feasibility and acute toxicity of radical hypo-fractionated radiotherapy (RT) for elderly patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We conducted a retrospective evaluation of treatment with volumetric modulated arc therapy (VMAT) of elderly patients affected by stage III inoperable NSCLC. The dose prescription was 56 Gy in 20 fractions, 55 Gy in 22 fractions, or 50 Gy in 20 fractions. Target volume included only the primary lesion and the infiltrated lymph nodes. The primary end point was acute and late toxicity, while secondary end points were progression-free survival (PFS), and overall survival (OS). RESULTS: In all, 41 patients were included in this analysis. The mean age of the patients was 78.6 years, and 22 patients had staged IIIA while 19 patients had stage IIIB disease. All but one patient had pathological nodal involvement; 15 patients received chemotherapy before RT. Acute grade 1-2 toxicity was recorded in 25 (61%) patients. Late toxicity was recorded in 13 (32%) patients. No cases of G3 or G4 toxicity were recorded. Complete response was obtained in two (5%) patients, 26 (63%) showed a partial response, and two (5%) experience disease progression. At a mean follow-up of 9.9 months (range, 1.1-25.4), 17 patients had died from disease progression, one died from other causes, and 23 were alive. Median OS was 13.7 ± 1.5 months (95% CI: 10.7-16.7), OS at 12 and 18 months was 51.3 ± 9.5% and 35.1 ± 10.1%, respectively. Median PFS was 13.7 ± 2.3 months (95% CI: 9.1-18.2), and PFS at 12 and 18 months was 50.1 ± 9.9% and 38.9 ± 10.4%, respectively. CONCLUSION: Radical hypo-fractionated VMAT is a promising treatment for locally advanced NSCLC in the elderly. The use of hypo-fractionated radiotherapy for lung cancer in older patients can be considered a valuable approach, particularly for patients with poor performance status or refusing other treatment approaches.

Clinical results of stereotactic body radiotherapy (SBRT) in the treatment of isolated local recurrence of pancreatic cancer after R0 surgery: A retrospective study.

OBJECTIVE: To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. METHODS: A retrospective analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI>18 months. No cases of acute G3 toxicity or greater occurred. CONCLUSIONS: SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.

High-quality Linac-based Stereotactic Body Radiation Therapy with Flattening Filter Free Beams and Volumetric Modulated Arc Therapy for Low-Intermediate Risk Prostate Cancer. A Mono-institutional Experience with 90 Patients.

AIMS: The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer. MATERIALS AND METHODS: Biopsy-confirmed prostate cancer patients were enrolled, provided that they had the following characteristics: initial prostate-specific antigen (PSA) ≤ 20 ng/ml, Gleason Score < 7, International Prostate Symptom Score < 7. The treatment schedule was 35 Gy in five fractions, delivered with volumetric modulated arcs with flattening filter free beams. Toxicity was recorded according to CTCAE criteria v4.0. Biochemical failure was calculated according to the Phoenix definition. The Expanded Prostate Cancer Index Composite questionnaire was used to record health-related quality of life. RESULTS: Between December 2011 and March 2015, 90 patients were enrolled (53 low risk, 37 intermediate risk). The median age was 71 years (range 48-82). In total, 58 (64.5%) of the patients had Gleason Score=6, the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml (range 2.7-17.0). Acute toxicity was mild, with 32.2 patients presenting grade 1 urinary toxicity and 32.2% of patients presenting grade 2 urinary toxicity, mainly represented by urgency, dysuria and stranguria. Rectal grade 1 toxicity was found in 15.5% of patients, whereas grade 2 toxicity was recorded in 6.6% of patients. Regarding late toxicity, grade 1 proctitis was recorded in 11.1% of patients and grade 1 urinary in 38.8%; only two events of grade 2 urinary toxicity were observed (transient urethral stenosis, resolved by a 24 h catheterisation). At a median follow-up of 27 months (6-62 months) only two intermediate risk patients experienced a biochemical failure. Health-related quality of life revealed a slight worsening in all the domains during treatment, with a return to baseline 3 months after treatment. CONCLUSIONS: Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life.

A case-control study of quality of life and functional impairment in women with long-standing vertebral osteoporotic fracture.

There have been several studies of the impact of vertebral osteoporotic fracture on the quality of life and functionality of individual subjects. To date, however, no direct comparisons with age-matched normal subjects without vertebral fracture have been made. The radiographs of 145 female clinic patients with vertebral fractures were reviewed by the study physicians. The controls were recruited from the electoral role and by media appeal. One hundred and sixty-seven women had radiographs taken to determine those without vertebral fracture. Fracture subjects and controls had to be ambulant and were excluded if they had significant radiologic evidence of degenerative disk or joint disease of the spine. One hundred cases and one hundred controls were matched by 5-year age groups. The number, position and severity of the vertebral fracture on the lateral radiographs of the cases was recorded. Quality of life was measured using the Short Form-36 (SF-36) (maximum score 100) and a utility score calculated from these results (maximum score 1). Two measurements of functionality were employed: the Modified Barthel Index (MBI) to assess the activities of daily living (maximum score 100) and the Timed 'Up & Go' (TUG) that measured the time taken for the subject to rise from sitting in a chair, walk 3 m along a line, return to the chair and sit down. The fracture subjects had 2.9 +/- 1.6 (mean +/- SD) vertebral fractures and the time since last fracture was 5.1 +/- 4.8 years. The SF-36 physical function component summary index results were: fracture subjects 36 +/- 11, controls 48 +/- 9 (p < 0.001). The SF-36 mental health component summary index results were: fracture subjects 50 +/- 11, controls 54 +/- 8 (p < 0.05). The utility scores were: fracture subjects 0.64 +/- 0.08, controls 0.72 +/- 0.07 (p < 0.001). The MBI results were: fracture subjects 97 +/- 5, controls 99 +/- 1 (p < 0.01). The TUG results were: fracture subjects 13.8 +/- 7.3 s, controls 10.1 +/- 4.1 s (p < 0.01). TUG and MBI scores correlated well with SF-36 scores; however, no domain of the SF-36 or functional measure correlated with either the number of vertebral fractures or the time since last vertebral fracture. Thus, clinically reported vertebral fractures impair both the quality of life and functionality of these subjects. The adverse impact of vertebral fracture on quality of life and functionality needs to be recognized by medical practitioners, subjects and the community, so that adequate health resources can be devoted to the prevention and treatment of this debilitating condition condition.