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.

Positron emission tomography for staging locally advanced cervical cancer and assessing intensity modulated radiotherapy approach.

AIMS: To evaluate toxicity and outcome of concomitant chemotherapy and intensity modulated radiotherapy (IMRT) with 18-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) based simultaneous integrated boost (SIB) of locally advanced cervical cancer (LACC). METHODS: Patients with LACC underwent chemo-radiation with IMRT and SIB. Staging and follow-up were performed with clinical evaluation and CT, MRI, 18FDG-PET/CT. SIB was done on positive nodes with 18FDG-PET/CT based planning. CT-based planning high-dose-rate brachytherapy (HDR-BT) was delivered as subsequent boost to the primary tumor. Cisplatin concomitant chemotherapy was administered during IMRT. RESULTS: Fourteen patients with cervical cancer were prospectively recruited between August 2014 and June 2017, 13 (93%) had a LACC, one (7%) patient was not evaluable because 18FDG-PET/CT evidenced metastases to the liver undetected by previous CT/MRI. Patients had a median age of 59 years, a median Karnofsky performance status of 100%, and a prevalence of squamous cell carcinoma histology (85%). SIB was delivered on 23 positive lymph nodes. IMRT median dose to the pelvis was 48.6 Gy in 27 fractions, SIB median dose 54 Gy in 27 fractions, HDR-BT boost median dose 21 Gy in 3 fractions. After a median follow-up of 30 months, 2-year local control and distant control were 86% and 86%, respectively. There were no grade 4 acute and/or late toxicities. CONCLUSIONS: The 18FDG-PET/CT influenced stage assessment and RT treatment planning due to its high specificity in distant metastases and nodal involvement detection. The IMRT with SIB for positive nodes was an effective therapy with acceptable toxicity in LACC.

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.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas With Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE: The proximity or overlap of planning target volume (PTV) and organs-at-risk (OARs) poses a major challenge in stereotactic body radiation therapy (SBRT) of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality. METHODS AND MATERIALS: A multiparametric specification of desired target doses (gross target volume [GTV]D50%, GTVD99%, PTVD95%, and PTV0.5cc) with 2 prescription doses of GTVD50% = 5 × 9.2Gy (46 Gy) and GTVD50% = 8 × 8.25 Gy (66 Gy) and OAR limits were distributed with planning computed tomography and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, replanning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion. RESULTS: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTVD50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTVD99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTVD50% prescription was performed by 95% of planners within 2%, and GTVD99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks. CONCLUSIONS: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training.

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.

Patient specific quality assurance in SBRT: a systematic review of measurement-based methods.

This topical review focuses on Patient-Specific Quality Assurance (PSQA) approaches to stereotactic body radiation therapy (SBRT). SBRT requires stricter accuracy than standard radiation therapy due to the high dose per fraction and the limited number of fractions. The review considered various PSQA methods reported in 36 articles between 01/2010 and 07/2022 for SBRT treatment. In particular comparison among devices and devices designed for SBRT, sensitivity and resolution, verification methodology, gamma analysis were specifically considered. The review identified a list of essential data needed to reproduce the results in other clinics, highlighted the partial miss of data reported in scientific papers, and formulated recommendations for successful implementation of a PSQA protocol.

Reliability of algebraic sum to evaluate adjuvant pelvic radiotherapy and vaginal cuff brachytherapy cumulative doses in uterine cancers.

Purpose: To evaluate the reliability of algebraic sum with respect to rigid fusion of treatment plans related to adjuvant external beam pelvic radiotherapy (APR) and vaginal cuff high-dose-rate brachytherapy (BT) in uterine cancer patients. Material and methods: For algebraic sum, APR and BT doses were mathematically added. Rigid fusion was realized overlapping computed tomography (CT) images of APR and BT treatment plans. Rectum and bladder were considered reference organs at risk (OARs). Following dose (D) parameters were examined: Dmax (0.5 cc), D20% and D50% for rectum, Dmax (0.5 cc) and D50% for bladder; for each parameter, differences between the two adopted methods were reported as Δ-values. Results: Twenty uterine cancer patients submitted to radical surgery followed by APR plus vaginal cuff BT were reviewed. APR was done with a dose of 25 × 2 Gy. All patients also receveid a vaginal cuff boost with BT at the dose of 2 × 5 Gy. Differences between mean cumulative doses calculated with rigid fusion and algebraic sum were evaluated. For the rectum and bladder ΔD50%, there were no significant differences, and BT contribution resulted minimal. An apparent significant difference value was registered in bladder ΔDmax (0.5 cc). No toxicity was observed. Conclusions: In uterine cancer patients submitted to APR and vaginal cuff BT, algebraic sum and rigid plan fusion of doses allowed to obtain similar results in evaluating cumulative OARs' doses. Further investigations and increased number of patients are recommended to confirm our findings.

Treatment of recurrent glioblastoma with stereotactic radiotherapy: long-term results of a mono-institutional trial.

AIMS AND BACKGROUND: Few clinical data exist concerning normal brain tissue tolerance to re-irradiation. The present study evaluated long-term outcome of 22 recurrent glioblastoma patients re-irradiated with radiosurgery or fractionated stereotactic radiotherapy. METHODS: Twenty-two patients were treated with radiosurgery (13, 59%) or fractionated stereotactic radiotherapy (9, 41%) for 24 lesions of recurrent glioblastoma. The male/female ratio was 14:8, median age 55 years (range, 27-81), and median Karnofsky performance status 90 (range, 70-100). The majority of the cases (77%) was in recursive partitioning analysis classes III or IV Radiosurgery or fractionated stereotactic radiotherapy was chosen according to lesion size and location. RESULTS: Median time between primary radiotherapy and re-irradiation was 9 months. Median doses were 17 Gy and 30 Gy, whereas median cumulative normalized total dose was 141 Gy and 98 Gy for radiosurgery and fractionated stereotactic radiotherapy, respectively. All patients submitted to radiosurgery had a cumulative normalized total dose of more than 100 Gy, whereas only a few (44%) of fractionated stereotactic radiotherapy patients had a cumulative normalized total dose exceeding 100 Gy. Median follow-up from re-irradiation was 54 months. At the time of analysis, all patients had died. After re-irradiation, 1 (4%) lesion was in partial remission, 16 (67%) lesions were stable, and the remaining 7 (29%) were in progression. Median duration of response was 6 months, and median survival from re-irradiation 11 months. Three of 13 (23%) patients submitted to radiosurgery developed asymptomatic brain radionecrosis. The cumulative normalized total dose for the 3 patients was 122 Gy, 124 Gy, and 141 Gy, respectively. In one case, the volume of the lesion was large (14 cc), and in the other 2 the interval between the first and second cycle of radiotherapy was short (5 months). CONCLUSIONS: Re-irradiation with radiosurgery and fractionated stereotactic radiotherapy is feasible and effective in recurrent glioblastoma patients. Apart from the importance of an accurate patient selection, cumulative radiotherapy dose and a correct indication for radiosurgery or fractionated stereotactic radiotherapy must be taken into account to avoid brain toxicity.

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.

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.

The influence of basic plan parameters on calculated small field output factors - A multicenter study.

PURPOSE: The influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study. METHODS AND MATERIALS: Three computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm2 field sizes (FSs) (normalized to 10x10 cm2 FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs. RESULTS: A total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible. CONCLUSIONS: Modern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs.

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.

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.

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.

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.

Multicentre treatment planning inter-comparison in a national context: The liver stereotactic ablative radiotherapy case.

PURPOSE: To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences. METHODS: Dose prescription was 75 Gy in 3 fractions, normalised at 67%-95% isodose. RESULTS: Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. CONCLUSIONS: The human factor and the constraints imposed to the target volume have a greater dosimetric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial.