Stereotactic Ablative Radiation Therapy for Oligometastatic Ovarian Cancer Lymph Node Disease: The MITO-RT3/RAD Phase II Trial.

PURPOSE: MITO-RT3/RAD (NCT04593381) is a prospective multicenter phase 2 trial designed to assess the effectiveness and safety of stereotactic body radiation therapy (SBRT) in patients who received diagnoses of oligometastatic ovarian cancer. In this report, we provide the results of the trial in the setting of lymph node disease. METHODS AND MATERIALS: The primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival (PFS), overall survival, treatment-free interval, and toxicity rates. The sample size was based on a previous study reporting an average 70.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 70.0% to 85.0%, with an α error of 0.05 (one-side) and a ß error of 0.1. RESULTS: The study met its primary endpoint of a statistically significant improvement in CR. One hundred thirty-five patients with 249 lesions were enrolled across 15 institutions from May 2019 to November 2023. CRs were observed in 194 lesions (77.9%), partial responses in 40 (16.1%), stable disease in 14 (5.6%), and progressive disease in 1 lesion (0.4%). The objective response rate was 94%, with an overall clinical benefit rate of 99.6%. CR lesions exhibited a significantly higher LC rate than partial or not responding lesions (12-month LC: 92.7% vs 63.1%, P < .001). The 12-month actuarial rates for PFS and for overall survival were 36.6% (CR, 38.3% vs not-CR, 18.8%; P, .022) and 97.2% (CR, 97.8% vs not-CR, 93.8%; P, .067), respectively. The 12-month actuarial rate for treatment-free interval was 52.7% (CR, 58.4% vs not-CR, 24.4%; P, .004). CR was substantially associated with higher PFS (P, .036) and treatment-free interval (P, .006) rates in the univariate analysis. Twenty-three patients (17.0%) experienced mild acute toxicity. Late toxicity was reported in 9 patients (6.7%), mostly grade 1. CONCLUSIONS: This trial confirms the efficacy of ablative SBRT, with minimal toxicity observed. SBRT offered a high CR rate, promising long-term outcomes, and a significant systemic therapy-free survival period for complete responders.

Efficacy of stereotactic body radiotherapy and response prediction using artificial intelligence in oligometastatic gynaecologic cancer.

PURPOSE: We present a large real-world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory machine learning analysis was performed. METHODS: A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2-year actuarial LC, DMFS, PFS, and OS. RESULTS: 501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose≥78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2-year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2-year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR. CONCLUSIONS: CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology.

Can interventional radiotherapy (brachytherapy) be an alternative to surgery in early-stage oral cavity cancer? A systematic review.

PURPOSE: Brachytherapy (BT), also known as interventional radiotherapy (IRT), has proven its utility in the treatment of localized tumors. The aim of this review was to examine the efficacy of modern BT in early-stage oral cavity cancer (OCC) in terms of local control (LC), overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and safety. METHODS: The SPIDER framework was used, with sample (S), phenomena of interest (PI), design (D), evaluation (E), and research type (R) corresponding to early-stage oral cavity cancer (S); BT (PI); named types of qualitative data collection and analysis (D); LC, OS, DFS, CSS, and toxicity (E); qualitative method (R). Systematic research using PubMed and Scopus was performed to identify full articles evaluating the efficacy of BT in patients with early-stage OCC. The studies were identified using medical subject headings (MeSH). We also performed a PubMed search with the keywords "brachytherapy oral cavity cancer, surgery." The search was restricted to the English language. The timeframe 2002-2022 as year of publication was considered. We analyzed clinical studies of patients with OCC treated with BT alone only as full text; conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. RESULTS: The literature search resulted in 517 articles. After the selection process, 7 studies fulfilled the inclusion criteria and were included in this review, totaling 456 patients with early-stage node-negative OCC who were treated with BT alone (304 patients). Five-year LC, DFS, and OS for the BT group were 60-100%, 82-91%, and 50-84%, respectively. CONCLUSION: In conclusion, our review suggests that BT is effective in the treatment of early-stage OCC, particularly for T1N0 of the lip, mobile tongue, and buccal mucosa cancers, with good functional and toxicity profiles.

Efficacy and Safety of Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer (MITO-RT2/RAD): A Large, Real-World Study in Collaboration With Italian Association of Radiation Oncology, Multicenter Italian Trials in Ovarian Cancer, and Mario Negri Gynecologic Oncology Group Groups.

PURPOSE: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiation therapy in a large cohort of patients with oligometastatic/persistent/recurrent uterine cancer. METHODS AND MATERIALS: Clinical and radiation therapy data from several radiation therapy centers treating patients by stereotactic body radiation therapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, and 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. Primary endpoints were the rate of complete response to stereotactic body radiation therapy, and the 2-year actuarial local control rate "per-lesion" basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. RESULTS: In the study, 157 patients with oligometastatic/persistent/recurrent uterine cancer bearing 272 lesions treated by stereotactic body radiation therapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in 5 fractions (range, 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), and 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤13.7 cc) and total dose (BED10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) "per-lesion" basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR; P < .001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, and patients with NCR had a 2-year rate of 17.6% (P < .001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared with 56.5% for NCR patients (P <.001). Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%. CONCLUSIONS: The efficacy of stereotactic body radiation therapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach.

Vaginal Toxicity Management in Patients with Locally Advanced Cervical Cancer following Exclusive Chemoradiation-A Nationwide Survey on Knowledge and Attitudes by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gynecology Study Group.

Background and Objective: Exclusive radiotherapy, including external beam radiotherapy (EBRT) and interventional radiotherapy/brachytherapy (IRT/BT), with concurrent cisplatin-based chemotherapy, represents the standard of care in patients with locally advanced cervical cancer (LACC). The emerging topic of vaginal toxicity has become a key endpoint in LACC management, although different approaches and non-standardized procedures were available. Our aim was to analyze a nationwide study of the attitudes of Italian gynecological radiation oncology teams in the management of LACC patients' vaginal toxicities. Methods: A nationwide survey of radiation oncologists specializing in the treatment of gynecological malignancies was performed, using the free SurveyMonkey platform, consisting of 26 items. The questionnaire was proposed by the Italian Association of Radiation Oncologists (AIRO) gynecological working group to all 183 Italian radiation oncology institutions, as per AIRO's website. Results: Fifty-eight questionnaires (31%) were completed and returned. The assessment of acute and late vaginal toxicities was systematic in 32 (55.2%) and 26 (44.8%) centers, respectively. In the case of EBRT, 70.7% of centers, according to the contouring and treatment plan data, did not contour the vagina as an organ at risk (OAR). Vaginal dose constraints were heterogeneous for both EBRT and IRT/BT. Local treatment to prevent vaginal toxicity was prescribed by 60.3% of radiation oncologists, mostly vaginal hyaluronic acid cream, and one center recommended vaginal estrogen preparations. During follow-up visits, vaginal toxicity was considered an issue to be investigated always (n = 31) or in sexually active women only (n = 11). Conclusions: This survey showed that wide variation exists with regard to recording and treating vaginal toxicity after exclusive chemoradiation for cervical cancer, underscoring the need to develop more comprehensive guidelines for contouring e-dose reporting of the vagina, so as to implement clinical approaches for vaginal toxicity.

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.

An Italian survey on "palliative intent" radiotherapy.

Background: The aim of this paper is to provide a comprehensive overview of the scenario on radiotherapy (RT) delivered with palliative intent in Italy. Materials and methods: A structured online questionnaire was submitted to Italian radiation oncologists in order to explore the clinical practice in different areas of palliation, namely: bone, lung, brain, liver, and emergencies suitable to RT. Results: 209 radiation oncologists took part in the study. Stereotactic body irradiation was found to be the preferred technique in lung and liver metastases, whereas 3D conformal RT was registered as the technique of choice for bone and brain metastases. The majority (98%) of participants stated to treat mainly radiotherapy emergencies with 3D conformal RT at doses ranging from 25 to 50 Gy. Re-irradiation is delivered by the majority of respondents, whereas post-treatment follow-up is done only by 51.4% of them. Conclusions: This nationwide study highlights some heterogeneity among Italian radiation oncologists regarding treatment and follow-up of metastatic cancer patients.

Stereotactic radiotherapy for lung oligometastases.

30-60% of cancer patients develop lung metastases, mostly from primary tumors in the colon-rectum, lung, head and neck area, breast and kidney. Nowadays, stereotactic radiotherapy (SRT ) is considered the ideal modality for treating pulmonary metastases. When lung metastases are suspected, complete disease staging includes a total body computed tomography (CT ) and/or positron emission tomography-computed tomography (PET -CT ) scan. PET -CT has higher specificity and sensitivity than a CT scan when investigating mediastinal lymph nodes, diagnosing a solitary lung lesion and detecting distant metastases. For treatment planning, a multi-detector planning CT scan of the entire chest is usually performed, with or without intravenous contrast media or esophageal lumen opacification, especially when central lesions have to be irradiated. Respiratory management is recommended in lung SRT, taking the breath cycle into account in planning and delivery. For contouring, co-registration and/or matching planning CT and diagnostic images (as provided by contrast enhanced CT or PET-CT ) are useful, particularly for central tumors. Doses and fractionation schedules are heterogeneous, ranging from 33 to 60 Gy in 3-6 fractions. Independently of fractionation schedule, a BED10 > 100 Gy is recommended for high local control rates. Single fraction SRT (ranges 15-30 Gy) is occasionally administered, particularly for small lesions. SRT provides tumor control rates of up to 91% at 3 years, with limited toxicities. The present overview focuses on technical and clinical aspects related to treatment planning, dose constraints, outcome and toxicity of SRT for lung metastases.

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.

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-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.

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.

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.

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO).

INTRODUCTION: The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. METHODS: Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months. RESULTS: Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p  ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. CONCLUSION: our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

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.

Stereotactic body radiotherapy in oligometastatic prostate cancer patients with isolated lymph nodes involvement: a two-institution experience.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) is emerging as a treatment option in oligometastatic cancer patients. This retrospective study aimed to analyze local control, biochemical progression-free survival (b-PFS), and toxicity in patients affected by isolated prostate cancer lymph node metastases. Finally, we evaluated androgen deprivation therapy-free survival (ADT-FS). METHODS: Forty patients with 47 isolated lymph nodes of recurrent prostate cancer were treated with SBRT. Mostly, two different fractionation schemes were used: 5 × 7 Gy in 23 (48.9 %) lesions and 5 × 8 Gy in 13 (27.7 %) lesions. Response to treatment was assessed with periodical PSA evaluation. Toxicity was registered according to RTOG/EORTC criteria. RESULTS: With a mean follow-up of 30.18 months, local control was achieved in 98 % of the cases, with a median b-PFS of 24 months. We obtained a 2-year b-PFS of 44 % with 40 % of the patients ADT-free at last follow-up (mean value 26.18 months; range 3.96-59.46), whereas 12.5 % had a mean ADT-FS of 13.58 months (range 2.06-37.13). Late toxicity was observed in one (2.5 %) patient who manifested a grade 3 gastrointestinal toxicity 11.76 months after the end of SBRT. CONCLUSION: Our study demonstrates that SBRT is safe, effective, and minimally invasive in the eradication of limited nodal metastases, yielding an important delay in prescribing ADT.

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.