Re-irradiation for recurrent intracranial meningiomas: Analysis of clinical outcomes and prognostic factors.

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

STereotactic Ablative RadioTherapy in NEWly Diagnosed and Recurrent Locally Advanced Non-Small Cell Lung Cancer Patients Unfit for ConcurrEnt RAdio-Chemotherapy: Early Analysis of the START-NEW-ERA Non-Randomised Phase II Trial.

PURPOSE: This is a single arm phase 2 trial (Clinical trials.gov NCT05291780) to assess local control (LC) and safety of SAbR in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) unfit for concurrent chemo-radiation therapy (ChT-RT). METHODS: Neoadjuvant ChT was prescribed in fit patients. The tumor volume included primary tumor and any regionally positive node/s. The coprimary study endpoints were LC and safety. RESULTS: Between December 31, 2015, and December 31, 2020, 50 patients with LA-NSCLC were enrolled. Histology was squamous cell carcinoma and adenocarcinoma (ADC) in 52% and 48%, respectively. Forty (80%) patients had ultracentral tumor. Twenty-seven (54%) received neoadjuvant ChT and 7 (14%) adjuvant durvalumab. Median prescribed dose was 45 Gy (range, 35-55) and 40 Gy (35-45) in 5 daily fractions to tumor and node/s, respectively. After a median follow-up of 38 months (range, 12-80), 19 (38%) patients had experienced local recurrence (LR) at a median time of 13 months (range, 7-34). The median LR-free survival (FS) was not reached (95% confidence interval [CI], 28 to not reached). The 1-, 2-, and 3-year LR-FS rates were 86% ± 5%, 66% ± 7%, and 56% ± 8%, respectively. At last follow-up, 33 (66%) patients were alive. Median overall survival (OS) was 55 months (95% CI, 43-55 months). The 1-, 2-, and 3-year OS rates were 94% ± 3%, 79% ± 6%, and 72% ± 7%, respectively. No patients developed ≥ grade (G) 3 toxicity. ADC (hazard ratio [HR], 3.61; 95% CI, 1.15-11.35) was a significant predictor of better LC, while OS was significantly conditioned by smaller planning target volumes (HR, 1.004; 95% CI, 1.001-1.010) and tumor, node, and metastasis stage (HR, 4.8; 95% CI, 1.34-17). CONCLUSIONS: Patients with LA-NSCLC treated with SABR had optimal LC and promising OS in absence of ≥G3 toxicity. Our early outcomes would suggest the feasibility of using this approach in patients with LA-NSCLC unfit for concurrent ChT-RT.

AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Stereotactic radiotherapy for brain oligometastases.

Brain metastases, the most common metastases in adults, will develop in up to 40% of cancer patients, accounting for more than one-half of all intracranial tumors. They are most associated with breast and lung cancer, melanoma and, less frequently, colorectal and kidney carcinoma. Magnetic resonance imaging (MRI) is the gold standard for diagnosis. For the treatment plan, computed tomography (CT ) images are co-registered and fused with a gadolinium-enhanced T1-weighted MRI where tumor volume and organs at risk are contoured. Alternatively, plain and contrast-enhanced CT scans are co-registered. Single-fraction stereotactic radiotherapy (SRT ) is used to treat patients with good performance status and up to 4 lesions with a diameter of 30 mm or less that are distant from crucial brain function areas. Fractionated SRT (2-5 fractions) is used for larger lesions, in eloquent areas or in proximity to crucial or surgically inaccessible areas and to reduce treatment-related neurotoxicity. The single-fraction SRT dose, which depends on tumor diameter, impacts local control. Fractionated SRT may encompass different schedules. No randomized trial data compared the safety and efficacy of single and multiple fractions. Both single-fraction and fractionated SRT provide satisfactory local control rates, tolerance, a low risk of transient acute adverse events and of radiation necrosis the incidence of which correlated with the irradiated brain volume.

Stereotactic Body Radiotherapy in Contralateral Kidney Oligometastasis From Renal Cell Carcinoma in a Nephrectomized Patient.

Background: Renal cell carcinoma (RCC) frequently metastasizes to distal organs such as the lungs, abdomen, bones, and brain. Although rare cases of adrenal gland metastasis from RCC have been described, to our knowledge, no cases have reported the use of stereotactic body radiotherapy (SBRT) in contralateral kidney oligometastasis in a nephrectomized patient with RCC. Case Report: We report a rare case of single contralateral renal metastasis from RCC in a 65-year-old female that occurred 1 year after right radical nephrectomy. At diagnosis of relapse, the patient received targeted therapy with sunitinib for 9 consecutive months, resulting in a partial regression of renal metastasis. To preserve the organ and consolidate response, SBRT was administered to the residual mass. Targeted therapy was temporarily discontinued 15 days before and after SBRT. Total SBRT dose was 40 Gy in 5 daily fractions given with volumetric modulated arc and image-guided technique. Three months later, magnetic resonance imaging documented a complete regression of disease, a result that persisted at the last follow-up 19 months after SBRT. Conclusion: The combination of sequential targeted therapy and SBRT provided an excellent outcome in a patient with a solitary kidney who experienced contralateral kidney metastasis from RCC. This treatment approach was well tolerated and controlled the disease.

Long-Lasting Palliation of Bone Oligometastatic Prostate Cancer After Repeated Stereotactic Body Radiotherapy.

Background: Oligometastatic disease has emerged as a distinct clinical state, with a tumor burden intermediate between localized and extensive systemic disease. Oligometastatic prostate cancer has generally been classified as ≤3 metastases in bone or lymph nodes only. Improvements in diagnostic modalities such as functional imaging allow a greater frequency of oligometastases diagnosis. Selected bone oligometastatic prostate cancer patients can be treated with metastasis-directed stereotactic body radiotherapy (SBRT) rather than androgen deprivation therapy (ADT). We describe a case representative of this scenario. Case Report: A 72-year-old male underwent surgery and salvage radiotherapy for a Gleason score 7 (3+4) adenocarcinoma confined in the prostate but with microscopic-positive surgical margins. Eight months after the end of radiotherapy, bone metastasis was diagnosed and treated with SBRT only because the patient refused ADT. In the subsequent 10 years, 6 more courses of SBRT were administered for new bone oligometastases encountered during follow-up. Neither local recurrence nor toxicity was observed after SBRT treatments. The patient, who is now 83 years old, has a Karnofsky Performance Status score of 90% and has preserved a satisfactory potentia coeundi. Conclusion: SBRT is a promising treatment for patients with bone oligometastatic prostate cancer, providing a high control rate within the irradiated volume and low toxicity. The ability to administer consecutive SBRT courses when new bone oligometastases are encountered in other sites can delay initiation of ADT. This case report reflects emerging trends for bone oligometastases treatment with metastasis-directed radiotherapy.

Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO.

BACKGROUND: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology). METHODS: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT. RESULTS: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate. CONCLUSIONS: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.

Clinical characterization of glioblastoma patients living longer than 2 years: A retrospective analysis of two Italian institutions.

AIM: Despite the advances in surgery and radio-chemotherapy, the prognosis of glioblastoma (GBM) remains poor with about 13% of patients alive at 24 months. METHODS: A total of 75 long-term survivors (LTS), defined as alive at least 24 months from diagnosis, were retrospectively analyzed. Overall survival (OS) and recurrence-free-survival (RFS) were calculated and related to patient characteristics and treatment received. RESULTS: Median age and Karnofsky performance status (KPS) were 56 years and 100%, respectively. After surgery (gross tumor resection-GTR in 62, 83% patients), all LTS received concomitant temozolomide (TMZ) with radiotherapy and 70 (93%) adjuvant TMZ. Of these, 10 (13%) discontinued TMZ prior the completion of 6 cycles, 37 (49%) received 6 cycles and 23 (31%) >6 cycles. Sixty-nine (92%) patients experienced a first tumor recurrence at a median time of 21 months. Of these, 32 (46%) were submitted to a second surgery, 34 (49%) to other no-surgical treatments and 3 (5%) only supportive care. At multivariate analysis, OS was significantly improved by second surgery after first recurrence (P = 0.0032) and by cycles of adjuvant TMZ > 6 versus ≤6 (P = 0.05). More than six cycles of TMZ significantly conditioned also first RFS (P = 0.011) and second RFS (P = 0.033). CONCLUSION: The large majority of LTS had <65 years, had a high KPS and received GTR. OS and RFS resulted significantly related to an extended administration of adjuvant TMZ (>6 cycles) and a second surgery in case of recurrence.

Brain metastases from primary colorectal cancer: is radiosurgery an effective treatment approach? Results of a multicenter study of the radiation and clinical oncology Italian association (AIRO).

OBJECTIVES: The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS). METHODS: 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too. RESULTS: The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival. CONCLUSION: SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs. ADVANCES IN KNOWLEDGE: The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.

Long-term palliation of lymph node oligometastatic ovarian carcinoma after repeated stereotactic body radiotherapy: case report.

INTRODUCTION: Oligometastatic disease has emerged as an intermediate state between localized and systemic cancer. Improvements in diagnostic modalities such as functional imaging allow a greater frequency of oligometastases diagnosis. Patients with selected oligometastatic epithelial ovarian carcinoma (EOC) may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) rather than chemotherapy. CASE DESCRIPTION: We describe a 58-year-old woman who underwent surgery and chemotherapy for an EOC. The patient underwent 3 chemotherapy lines for recurrence of disease, but had allergic reactions and serious hematologic toxicity. During follow-up, lymph node oligometastases were diagnosed and treated with repeated SBRT because the patient refused further chemotherapy. No side effects were observed after each course of SBRT and the patient obtained complete response of all irradiated sites. CONCLUSIONS: SBRT is a promising treatment approach for recurrent oligometastatic EOC with a high control rate and irrelevant iatrogenic toxicity. The possibility to repeat SBRT courses when new oligometastases are encountered in other sites resulted in an adequate long-term palliation approach.

Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients.

OBJECTIVE: To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer. METHODS: 37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS). RESULTS: Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/ß ratio 10 Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity. CONCLUSION: SBRT was effective and safe in lung cancer adrenal metastases. A dose-response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies. ADVANCES IN KNOWLEDGE: SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.

Twelve-year results of LINAC-based radiosurgery for vestibular schwannomas.

PURPOSE: To report long-term outcomes of 53 patients with vestibular schwannomas (VS) submitted to a single high-dose LINAC-based radiosurgery (SRS) in our institution. METHODS: 48 (92%) patients were evaluable for clinical and MRI response as well as late toxicity. At a median follow-up of 12 years (range 2-16 years), local control (LC), hearing capacity, trigeminal and facial nerve function, and toxicity were assessed. Hearing capacity was classified according to the Gardner-Robertson scale, where class I-II patients had "serviceable hearing." RESULTS: Median dose of SRS was 16.5 Gy (range 13-20 Gy) and median tumor volume 1.7 cm3 (range 0.09-7.4 cm3). 35 (73%) patients were treated with SRS alone, in the remaining 13 (27%) patients, SRS was performed as salvage therapy for recurrent or progressive tumors after previous microsurgery. Before SRS, 44 patients (92%) had hearing loss and 25 (52%) had "non-serviceable" hearing. Tumor extension, classified with Koos categories, was grade I-II in 27 (56%) and grade III-IV in 21 (44%) cases. LC was 100% and hearing preservation in "serviceable hearing" patients was 91%. 4 (11%) patients developed incomplete and intermittent ipsilateral facial nerve palsy which regressed in a median time of 6 months. Trigeminal toxicity was registered in 11 (23%) patients, reversible in 6 (13%) and permanent in 5 (10%). Only Koos tumor grade III-IV significantly influenced late toxicity (p = 0.01). CONCLUSION: LC and hearing preservation after SRS were excellent. Toxicity proved acceptable. Although the median administered dose (16.5 Gy) was rather high, the only factor which significantly influenced late toxicity was Koos tumor grade III-IV.

LINAC-based radiosurgery for melanoma, sarcoma and renal cell carcinoma brain metastases.

BACKGROUND: The aim of this study was to report response, overall survival (OS) and toxicity in patients with radioresistant brain metastases (BM) treated with stereotactic radiosurgery (SRS). METHODS: Patients with renal cell carcinoma, melanoma and sarcoma with one to four brain metastases received SRS without whole brain radiotherapy. RESULTS: Fifty patients with 77 BM were treated. 46 (92%) patients with 71 BM were evaluable. Median follow-up was 67 months and median OS 11.8 months. At the time of analysis all patients had died. Brain control was conditioned by response to SRS (P<0.0001), while OS by histology (renal cell carcinoma versus melanoma and sarcoma) (P=0.04) and status of the tumour outside the brain (P=0.05). Treatment was well tolerated without more than grade 2 acute toxicity. CONCLUSIONS: Treatment of BM from radioresistant tumors with SRS assures good brain control and OS with low toxicity. Our data suggest a better prognosis associated to renal cell carcinoma histology.

Accelerated partial-breast irradiation with high-dose-rate brachytherapy: Mature results of a Phase II trial.

PURPOSE: The purpose of this study was to report mature clinical and cosmetic results of accelerated partial-breast irradiation with interstitial multicatheter high-dose-rate brachytherapy (HDR-BRT) in patients with early breast cancer. METHODS AND MATERIALS: 133 patients were recruited in a Phase II trial of exclusive HDR-BRT. Inclusion criteria were age ≥40 years, PS 0-2, unifocal invasive ductal cancer, intraductal cancer component <25%, negative axillary nodes, and tumor size ≤2.5 cm. Treatment schedule was 4 Gy twice a day up to a total dose of 32 Gy in eight fractions. RESULTS: Median age was 67 years (range, 42-85). There were 7 (5%) pT1a, 48 (36%) pT1b, 72 (54%) pT1c, and 6 (5%) pT2. Estrogen and progesterone receptors were positive in 119 (89%) and 93 (70%) patients, respectively. The median followup was 110 months (range, 12-163). After HDR-BRT, there were 3 (2%) in-field breast recurrences and 1 (1%) out-field breast recurrence. 5 (4%) patients developed contralateral breast cancer, another one (1%) isolated regional relapse in axillary node and 3 (2%) distant progression of disease. 19 (14%) patients reported a second primary cancer. 5-, 10-, and 13-year overall survival and cancer-specific survival were 95% and 100%, 84.5% and 100%, and 81.4% and 100%, respectively. Cosmetic outcome was excellent in 80% of cases. Late toxicity was significantly related to the skin administered doses (≤55% vs. > 55% of the prescribed dose, p < 0.05). CONCLUSIONS: Accelerated partial-breast irradiation delivered with HDR-BRT in selected patients with breast cancer was associated to high local control and survival with excellent cosmetic outcomes overall when skin dose was ≤55%.

A prospective phase II trial on reirradiation of brain metastases with radiosurgery.

PURPOSE: In our previous published trial on radiosurgery (SRS) of recurrent brain metastases (BM) after whole brain radiotherapy (WBRT), Karnofsky performance status (KPS) and administered dose conditioned outcome and late toxicity, respectively. Brain radionecrosis was registered in 6% of patients. With the aim to obtain similar satisfactory outcomes and limit toxicity, we started a phase II trial in which reirradiation of BM with SRS were done using a tighter patient selection. MATERIALS AND METHODS: Patients with BM recurring after WBRT were recruited for reirradiation with SRS. Only patients with good KPS (≥70), good neurologic functional score (NFS 0-1) and lesions with a diameter ≤20 mm were considered eligible for retreatment. Dose exceeding 20 Gy was never administered. RESULTS: The 59 patients reirradiated had 109 BM with a diameter range of 6-20 mm. Median interval between prior WBRT and SRS was 15 months and median SRS administered dose was 18 Gy (range 10-20 Gy). Complete and partial response (CR, PR) was obtained in 42% of patients with 2 years of control rate of 81%. Median overall survival (OS) after reirradiation was 14 months. No radionecrosis was detected. CONCLUSIONS: Analysis of our current trial compared with results of our previous data suggests that a tighter patient selection (KPS ≥ 70; NFS 0-1, BM with ≤20 mm of diameter) and SRS dose ≤20 Gy allowed a high OS rate, a good percentage of CR and PR which last for >2 years, and no brain radionecrosis.

Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study.

PURPOSE: We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. METHODS: 240 patients received APBI (4Gy, twice daily; total dose 32Gy). RESULTS: Median follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72). CONCLUSIONS: APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer.

PURPOSE: To report our experience on high-dose-rate brachytherapy (HDR-BT) in patients with stage I-III endometrial cancer unfit to surgery. MATERIAL AND METHODS: Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95), median Karnofsky performance status 90% (range, 60-100). Histology was endometrial adenocarcinoma in 14 (82%), and non-endometrial in 3 (18%) patients. In 15 (88%) patients, clinical stage was I and in remaining 2 (12%) was III. All patients were evaluated with computed tomography (CT) and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC) was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. RESULTS: Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT) combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131), 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS) at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adenocarcinoma) LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma) was 100% at 1 and 6 years (p = 0.05). Two (12%) patients had G2 acute toxicity and two others (12%) G1 late toxicity. CONCLUSIONS: Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection), it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology.

Lung reirradiation with stereotactic body radiotherapy.

PURPOSE: We examined safety and efficacy of stereotactic body radiotherapy (SBRT) in reirradiation for lung recurrent lesions (LRLs). MATERIALS AND METHODS: Eighteen patients, 4 with lung local failure from primary non-small cell lung carcinomas and 14 with lung metastases, were reirradiated with SBRT for 29 LRLs. Doses were recalculated to an Equivalent Dose of 2 Gy per fraction (EQD2) and α/ß ratio was assumed to be Gy10 for primary and metastatic lung tumors and Gy3 for organ at risk. Cumulative administered doses were calculated adding doses of prior radiotherapy and reirradiation. RESULTS: Peripherally located lesions received 5 fractions of 8-10 Gy, while centrally ones lower doses (5 fractions of 5-8 Gy). Cumulative EQD2 did not exceed 198 Gy10 and reirradiated volumes were rather small (median 18 cc). Local control was obtained for all patients except one and lasted medially 43 months. Median overall survival was 40 months from reirradiation. Only acute grade 1 toxicity was recorded. CONCLUSIONS: Reirradiation of LRLs with SBRT was feasible and effective. It is important to appropriately select patient and to adopt organ at risk constrains considering cumulative doses.

Long-term outcome of moderate hypofractionated stereotactic radiotherapy for meningiomas.

PURPOSE: The aim of this work was to evaluate long-term results of moderate hypofractionated stereotactic radiotherapy (hFSRT) for intracranial meningiomas. PATIENTS AND METHODS: In all, 77 consecutive patients with 80 lesions were included. Median age was 65 years (range 23-82 years), male/female ratio was 21/56, and the median Karnofsky performance status was 90 (range 60-100). In 31 lesions (39 %), diagnosis was based upon clinical and radiological data; 37 lesions were histologically proven as World Health Organization (WHO) grade I and 12 grade II meningiomas. Median treatment volume was 23 cc. Prescribed doses were 45 Gy in 15 fractions of 3 Gy (15 × 3 Gy) or 42 Gy in 14 fractions of 3 Gy (14 × 3 Gy). RESULTS: After a median follow-up of 56 months, 49 (61 %) lesions received 14 × 3 Gy and 31 (39 %) 15 × 3 Gy. Local control (LC) rate remained unchanged at 84 % at 5 and 10 years. Overall survival and disease-specific survival (DSS) were 76 and 93 % at 5 years, 72 and 89 % at 10 years, respectively. With univariate analysis, previous surgery and WHO grade II tumor were negative prognostic factors for LC and DSS. With multivariate analysis only tumor grade was an independent prognostic factor for LC. No clinically significant acute and/or late toxicities were observed. CONCLUSION: Moderate hFSRT was effective and safe with an excellent tolerance profile. It can be an alternative treatment option for patients with recurrent or inoperable large meningiomas. The low number of fractions administered with hFSRT led to reduce treatment-related discomfort for patients. Grade II tumor and previous surgery were negative prognosis factors.