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.

Diagnostic and Therapeutic Management of Primary Orbital Neuroendocrine Tumors (NETs): Systematic Literature Review and Clinical Case Presentation.

BACKGROUND: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. METHODS: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical-pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant'Andrea Hospital, La Sapienza University of Rome, Italy. RESULTS: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. CONCLUSIONS: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival.

Hypofractionated Radiation Therapy (HFRT) of Breast/Chest Wall and Regional Nodes in Locally Advanced Breast Cancer: Toxicity Profile and Survival Outcomes in Retrospective Monoistitutional Study.

AIM: To evaluate the efficacy and safety of hypofractionated radiation therapy (HFRT) of the breast/chest wall and regional nodes in patients with locally advanced breast cancer and positive lymph nodes. MATERIALS AND METHODS: One hundred and twenty-two patients treated between October 2016 and March 2020 with HFRT were retrospectively reviewed. A total dose of 42.4 Gy was delivered to the chest wall and lymph nodes in 16 fractions of 2.65 Gy each, using the IMRT technique. Patients treated with breast-conserving surgery received an overdose (concomitant boost of 3 Gy daily) with the SIB (Simultaneous Integrated Boost) technique. RESULTS: Median age at diagnosis was 58 years (range 34-86 years) and median follow-up was 22 months (range 6-48 months). Overall survival (OS) at 1, 2 and 3 years was 100%, 97.3% and 90%, respectively. Disease-free survival (DFS) at 1, 2, and 3 years was 91.4%, 87%, and 84.8%, respectively. Distant metastasis-free survival (MFS) at 1, 2 and 3 years was 93.1%, 88% and 85.7%, respectively. Two patients (1.6%) experienced local recurrence on the chest wall during FUP. Twenty-one patients (17%) showed a grade 2 dermal toxicity, no grade 3 acute skin toxicity was found. Sixteen patients (13%) showed early-stage arm lymphedema (grade ≤ 2). Twenty-three patients (19%) showed a grade 2 late skin toxicity. Twenty patients (16%) had grade ≤ 2 late arm lymphedema. CONCLUSION: Given the excellent local control, survival rates and the low toxicity profile demonstrated, HFRT could be considered a valid therapeutic option in patients with locally advanced breast cancer.

Stereotactic body radiation therapy (SBRT) for patients with oligometastatic/oligoprogressive adrenal metastases: Outcomes and toxicities profile in a monoinstitutional study.

AIMS: To evaluate survival outcomes and toxicology profiles in oligometastatic/oligoprogressive patients treated with SBRT for adrenal metastases. METHODS: We retrospectively analyzed 25 metastatic adrenal lesions in 24 oligometastatic/oligoprogressive patients undergoing ablative Stereotactic Body Radiation Therapy (SBRT) between February 2010 and November 2019 in our department. The primary endpoint was overall survival (OS). Secondary endpoints were local overall response rate (ORR), acute and late toxicities. RESULTS: The most common primary tumor was non-small cell lung cancer (54%). Twenty-one patients received chemo or immuno-therapy. The median planning target volume (PTV) was 41.7 cm3. Median SBRT dose was 36 Gy. Median dose per fraction was 15 Gy. Median survival was 35-months with OS outcomes ranging from 6-months (100%), 1-year (87.5%) and 2-years (66.7%). ORR based on RECIST criteria was 66.5%. 12 patients experienced acute toxicities, mostly grade 1-2 (8 patients, 32%). CONCLUSIONS: SBRT for oligometastatic/oligoprogressive patients with adrenal metastases showed acceptable survival outcomes and a safe toxicity profile.

Stereotactic Body Radiation Therapy Boost in Patients With Cervical Cancer Ineligible for Brachytherapy.

Background: Standard treatment for locally advanced cervical cancer is external beam radiotherapy followed by brachytherapy (BT). Stereotactic body radiation therapy (SBRT) is a possible option for treating patients ineligible for BT. Patients and Methods: From October 2012 to July 2020, nine women with cervical cancer received SBRT to high-risk volumes. The Kaplan-Meier method was used to estimate the rates of overall and disease-free survival. Results: The median age was 52 years; 88% of patients had squamous carcinoma. Reasons for forgoing BT were cervical canal stenosis, treatment refusal and hematological disease. The median boost dose was 18 Gy and the median dose per fraction was 6 Gy. Median follow-up was 16 months. The median survival was 24 months, the actuarial 2-year OS rate was 70%, and median disease-free survival was 11 months. One grade 3 late vaginal toxicity was reported. No acute nor late grade 4 toxicities were observed. Conclusion: SBRT boost in patients with cervical cancer ineligible for BT led to acceptable survival outcomes and a safe toxicity profile.

Outcome Evaluation of HER2 Breast Cancer Patients with Limited Brain Metastasis.

BACKGROUND/AIM: To appraise the outcome of limited brain metastasis (BMs) from HER2 breast cancer. PATIENTS AND METHODS: The study cohort included sixty-six patients Treatments consisted of surgery followed by radiotherapy (RT), or radiosurgery (SRS/HSRS) or whole brain radiotherapy (WBRT). RESULTS: Surgery followed by RT was performed in 25.8% of patients, SRS/HSRS alone in 48.5%, and WBRT alone in 25.7%. The median follow-up time was 23.4 months and 32.5 months for alive patients. Local recurrence occurred in 16 (24.2%) patients. The median, 1-, 2-, 3-year local control were (median not reached=nr), 87.5%, 71.2%, and 63.0%. The median 1-, 2-, 3-year overall survival were 30.7 months (95%CI: 18.9-42.6 months), 78.5%, 57.4%, 43.3%. Karnofsky Performance Scale (KPS), number of BMs, local treatment performed, the presence of extracranial (EC) metastases at the time of BMs diagnosis, and the administration of trastuzumab affected survival. CONCLUSION: HER2BC patients with good performance status, controlled EC disease and single BM had better outcome. In this long-term survivor patients, local BMs treatment can affect survival.

Are three weeks hypofractionated radiation therapy (HFRT) comparable to six weeks for newly diagnosed glioblastoma patients? Results of a phase II study.

BACKGROUND: The current standard of care for newly diagnosed glioblastoma (GBM) is surgical resection, followed by radiation therapy (RT) with concurrent and adjuvant temozolomide chemotherapy (TMZ-CHT). The patients outcome is still poor. In this study we evaluated hypofractionated radiation therapy (HFRT), instead of standard fractionated radiation therapy, with concomitant and adjuvant TMZ chemotherapy, in terms of safety and effectiveness. METHODS: Patients with newly diagnosed GBM, Karnofsky performance scale (KPS) ≥70, and tumor up to 10 cm underwent maximal feasible surgical resection were treated. HFRT consisted of 60 Gy, in daily fractions of 4 Gy given 5 days per week for 3 weeks. The primary endpoints were overall survival (OS), progression free survival (PFS), and incidence of radiation induced brain toxicity. Secondary endpoint was the evaluation of neurocognitive function. RESULTS: A total of 97 patients were included in this phase II study. The median age was 60.5 years (range 23-77 years). Debulking surgery was performed in 83.5% of patients, HFRT was completed in all 97 patients, concurrent and adjuvant TMZ in 93 (95.9%). The median number of TMZ cycles was six (range 1-12 cycles). No severe toxicity occurred and the neuropsychological evaluation remained stable. At a median follow up time of 15.2 months the median OS time, 1,2-year OS rate were 15.9 months (95% CI 14-18), 72.2% (95% CI 62.1-80) and 30.4% (95% CI 20.8-40.6). Age, KPS, MGMT methylation status, and extent of surgical resection were significant factors influencing the outcome. CONCLUSION: HFRT with concomitant and adjuvant TMZ chemotherapy is an effective and safe treatment.

Stereotactic/hypofractionated body radiation therapy as an effective treatment for lymph node metastases from colorectal cancer: an institutional retrospective analysis.

OBJECTIVE: The colorectal cancer (CRC) might present loco-regional recurrence, including lymph-node metastasis. Stereotactic body radiotherapy (SBRT) is a non-invasive and well-tolerated ablative treatment. Aim of the present study is to evaluate efficacy and toxicity of SBRT with volumetric modulated arc therapy (VMAT) in this setting. METHODS: 35 patients presenting a total of 47 nodal recurrences from CRC, treated with VMAT-SBRT from 2008 to 2015, were selected. About three fourth of the treatments delivered 45 Gy in 6 daily fractions. End-points were the detection of toxicities, overall survival (OS), local control (LC), disease progression free incidence (DPFI) and disease free survival (DFS). Tumour response was assessed according to the RECIST criteria. RESULTS: Only Grade 1 and 2 toxicities were recorded. Median follow-up was 15 months (range 2-68). Local relapse was reported in 6 patients, regional relapse in 10 patients. Complete remission was reported in 20 cases (53%), partial remission in 14 (37%). Rates of LC at 1, 2 and 3 years were 85.3, 75.0 and 75.0%, respectively. At 1 year the actuarial OS was 100%, at 2 and 3 years was 81.4%. Median DFS was estimated in 16 months, with an incidence of 69.4, 33.3 and 19.4% at 1, 2 and 3 years, respectively. CONCLUSION: The use of the VMAT-SBRT in lymph-node recurrence of CRC could prevent severe complications and achieve satisfying rates of disease control. Advances in knowledge: The use of VMAT-SBRT is a viable approach for lymph-node recurrence of CRC.

Outcome evaluation of patients with newly diagnosed anaplastic gliomas treated in a single institution.

AIM: To evaluate the outcome of newly diagnosed anaplastic glioma patients treated in our institution in relation to the 2016 WHO classification suggestions. METHODS: This retrospective study included patients who underwent surgery plus adjuvant chemotherapy alone or concomitant and adjuvant chemoradiotherapy. Response was recorded using the Response Assessment in Neuro-Oncology criteria. RESULTS: 123 patients were analyzed. The median progression-free survival time and the 2, 3 and 5 years progression-free survival rate were 27 months, 65.5, 21.2 and 21.2%; the 2, 3 and 5 years overall survival rate were 89.7, 83.0 and 58.4%. From the univariate/multivariate analysis, the factors conditioning survival were Karnofsky performance scale, extent of resection, IDH1 mutation status and presence of 1p/19q codeletion. CONCLUSION: The choice of adjuvant treatment have to consider molecular assessment and, in our experience, the extent of surgical resection.

Maximize surgical resection beyond contrast-enhancing boundaries in newly diagnosed glioblastoma multiforme: is it useful and safe? A single institution retrospective experience.

The extent of surgical resection (EOR) has been recorded as conditioning outcome in glioblastoma multiforme (GBM) patients but no significant improvements were recorded in survival. The study aimed to evaluate the impact of EOR on survival, investigating the role of fluid-attenuated inversion recovery (FLAIR) abnormalities removal. 282 newly diagnosed GBM patients were treated with surgery followed by concurrent and adjuvant chemo-radiotherapy. The EOR was defined as: SUPr, in case of resection amounting to 100% of enhanced and FLAIR areas; gross total (GTR) in case of resection between 90 and 100% of enhanced areas with variable amount of FLAIR abnormalities; sub-total (STR), between 10 and 89%; biopsy (B) <10%. FLAIR-RTV was dichotomized in percentage values to identify the best separation threshold for progression free survival (PFS) and overall survival (OS). SUPr was obtained in 21 patients (7.4%), GTR in 60 (21.3%), STR in 143 (50.7%) and biopsy only in 58 (20.6%). The median, 1, 2-year PFS were 10.4 ± 0.4 months, 39.0 ± 3.0, and 17.0 ± 2.0%; the median, 1, 2-year OS were 14.5 ± 0.5 months, 63.3 ± 3.0, and 23.1 ± 3.1%. EOR was significantly influencing survival (p < 0.001). The median, 1, 2-year OS were 28.6 ± 5.2 months, 90.0 ± 6.0, 71.0 ± 10.0% for patients underwent SUPr vs. 16.2 ± 1.2 months, 81.0 ± 5.0, 24.0 ± 6.0% for GTR. The FLAIR removal threshold conditioning survival was 45%. Minor complications were recorded in 14 (5%) patients and major in 8 (2.8%). surgical resection beyond contrast-enhancing boundaries could represent a promising strategy to improve outcome in GBM patients. The identification of a FLAIR-RTV threshold can be useful in clinical practice and it was recorded as factor influencing survival.

Outcome Evaluation of Patients with Limited Brain Metastasis From Malignant Melanoma, Treated with Surgery, Radiation Therapy, and Targeted Therapy.

OBJECTIVE: The incidence of brain metastases from melanoma is increasing. Several effective treatment options are now available but what can be considered the optimal therapeutic strategy is not yet defined. We evaluated the outcome of patients with brain metastatic melanoma in terms of local control rate, brain distant progression, and overall survival. METHODS: The present retrospective study includes only patients with limited brain metastases (≤4) who underwent surgery plus stereotactic radiosurgery (SRS), or SRS alone. Surgical resection was performed in patients with good Karnofsky performance score, single large brain lesions, controlled extracranial disease, and SRS alone in all other cases. Supramargical resection was performed in all patients. The prescribed radiotherapy doses were 24 Gy/1 fraction and 30 Gy in 3-5 fractions for lesions >2.5 cm. Clinical outcome was evaluated by brain magnetic resonance imaging performed 2 months after radiotherapy and then every 3 months. RESULTS: From April 2011 to October 2015, 53 patients were treated. The median age was 54 years (range, 29-82 years). Most of patients had 1-2 brain metastases (86.8%). Twelve patients (22.6%) underwent surgical resection followed by SRS on the tumor bed, and 41 (77.4%) received SRS alone. The median follow-up time was 20.9 months (range, 5.7-61.3 months). The median, 1-, 2-, 3-year overall survival were 11.8 months, 47.2%, 28%, and 21.8%, respectively. Factors recorded as influencing survival were the number of brain metastases, the melanoma-specific graded prognostic assessment score, and BRAF mutated status. CONCLUSIONS: Our data identifier a subset of patients with a more favorable outcome who could take advantage of a more aggressive local approach followed by targeted therapy.

Role of stereotactic body radiation therapy for lung metastases from radio-resistant primary tumours.

OBJECTIVES: A retrospective analysis was performed on patients treated for lung oligo-metastatic disease from radio-resistant histology groups. METHODS: The primary end point was local control (LC), secondary end points were overall survival (OS) and progression free survival (PFS). Toxicity was scored according to CTCAE 4.03. RESULTS: 200 patients were analyzed: 49.5% of the cases derived from colorectal primary tumors, 20.5% from sarcomas, 12.0% from renal cell carcinoma and the rest from other mixed origin. The mean follow-up was 24.2 months. LC at 1 and 2 years was 91, 84.9%. Primary histology and the presence of extra-pulmonary disease had a significant impact on LC. OS at 1 and 2 years was 88.7, 65.4%. Primary histology, disease free interval, presence of extra-pulmonary disease, number of irradiated lung lesions and age showed a correlation with prognosis at univariate analysis. PFS at 1 and 2 years was 84, 57.7%. The presence of extra-pulmonary disease and the number of irradiated lung lesions correlated with prognosis. Treatment was well tolerated with no G3-4 acute or late toxicity recorded. CONCLUSION: Colorectal metastases showed a higher rate of local relapse. However, the factors mostly influencing prognosis were the presence of extra-pulmonary disease and the number of lung lesions.

Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma.

PURPOSE: We evaluated the relationship between 11C-methionine PET (11C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative 11C-METH PET were analysed. Semiquantitative evaluation of the 11C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). RESULTS: In all patients, the tumour was identified on 11C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. CONCLUSION: 11C-METH PET parameters are significantly correlated with histological grade and IDH1 mutation status in patients with glioma. Grade, pathological classification, molecular biomarkers, SUVmax and SUVratio were prognostic factors for PFS in this cohort of patients. The trial was registered with ClinicalTrials.gov (registration: NCT02518061).

Role of surgical resection in recurrent glioblastoma: prognostic factors and outcome evaluation in an observational study.

The role of surgical resection in progressive or recurrent glioblastoma multiforme (GBM) lack of high level of evidence. The aim of this evaluation was to assess the role of surgical resection in relapsing GBM, in relation to the extent of surgical resection (EOR) and the amount of residual tumor volume (RTV). Among patients treated for newly diagnosed GBM between September 2008-December 2014, 64 patients with recurrent GBM were included in this retrospective evaluation. All patients underwent surgical resection followed by adjuvant treatments, chemotherapy and/or radiotherapy Results were evaluated in terms of local control (LC) rate, progression free survival (PFS) and patients overall survival (OS). Gross total resection (GTR) (>90%) was achieved in 48 (75%) patients and subtotal resection (STR) in 16 (25%). RTV was 0 in 40 (62.5%) patients and >0 in 24 (37.5%). No severe postoperative morbidity occurred. The median LC time was 6.0 ± 0.1 months (95% CI 5.29-8.55), with a 1 and 2 years LC rate of 29.4 ± 6.9%. The median PFS time was 6.8 ± 0.8 months, with a 1 year PFS rate of 27.2 ± 7.2% (95% CI 14.2-41.9). The median OS time was 10.3 ± 0.5 months (95% CI 7.6-10.4) with a 1 and 2 years OS rate of 22.5 ± 6.7% (95% CI 10.9-36.6). On univariate analysis EOR and RTV were recorded as conditioning LC and survival. These data was confirmed also in multivariate analysis only for RTV (p < 0.01). Recurrent GBM can take advantage of repeated surgery in selected patients with younger age and good clinical status. The entity of surgical resection was confirmed as conditioning survival.

Volumetric modulated arc therapy for thoracic node metastases: a safe and effective treatment for a neglected disease.

PURPOSE: To evaluate the outcome of Stereotactic Body Radiation Therapy (SBRT) with Volumetric Modulated Arc Therapy (VMAT) for thoracic node metastases. RESULTS: 18 out of 29 patients presented with isolated thoracic node metastases with no other sites of disease. Median prescribed dose was 45Gy (range 30-60Gy).Acute toxicity was recorded as G0 in 28 patients, while one patient was scored as G1. Late toxicity was G0 in 26 patients, one patient was scored G1, one as G2, and one as G4 presented acute myocardial infarction.During follow up, the best local response was complete remission in 14 patients and partial remission in 11 patients. With a median follow up of 12 months (range 2-35) 9 patients died from disease progression, 10 were still alive with distant metastases, 5 had a locally controlled disease and 5 patients were disease free.The median OS estimated was 18 months (76%, 49% at one, two years). The median PFS was 9 months (28%, 17% at one, two years). MATERIALS AND METHODS: Twenty-nine patients with 32 thoracic nodes metastases were treated with SBRT in our institution. Toxicities and response were assessed. Overall Survival (OS) and Progression Free Survival (PFS) were evaluated. CONCLUSIONS: SBRT is an efficient treatment for thoracic node metastases.

Role of Surgical Resection in Patients with Single Large Brain Metastases: Feasibility, Morbidity, and Local Control Evaluation.

OBJECTIVE: The aim of this study was to evaluate the safety and the feasibility of surgery for single large brain metastases. METHODS: This retrospective study included 69 patients. All received a "supramarginal resection" according to functional boundaries, defined as a microsurgical excision with an extension larger at least 5 mm greater than the enhancing T1-weighted magnetic resonance imaging (MRI) sequence borders with dural attachment radicalization. Hypofractionated stereotactic radiosurgery on the tumor bed, using 30 Gy in 3 fractions, was performed within 1 month after surgery. Clinical outcome was evaluated at 30 days postoperative and by MRI performed every 3 months. The appearance of postoperative neurologic deficits, local control (LC), brain distant progression (BDP), and overall survival were evaluated. RESULTS: Clinical remission of symptomatology was obtained in 90.5% of patients. None of them had new neurologic deficits or worsening of preoperative functional status. No major complications or cerebrospinal fluid leakage occurred. No residual tumor was detected on postoperative MRI. The median follow-up was 24 months (range 4-33 months). The 1- to 2-year LC was 100%. Twenty-four (29% of) patients had new BDP, and 75% had extracranial progression. The median 1- to 2-year overall survival was 24 months, 91.3% and 73%. At the last observation time, 15 patients (21.7%) were dead and 54 patients (78.3%) were alive. CONCLUSION: Supramarginal resection along with dural attachment radicalization have proved to be safe and effective for selected patients with single large brain metastases.

Can advanced new radiation therapy technologies improve outcome of high grade glioma (HGG) patients? analysis of 3D-conformal radiotherapy (3DCRT) versus volumetric-modulated arc therapy (VMAT) in patients treated with surgery, concomitant and adjuvant chemo-radiotherapy.

BACKGROUND: To assess the impact of volumetric-modulated arc therapy (VMAT) compared with 3D-conformal radiotherapy (3DCRT) in patients with newly diagnosed high grade glioma in terms of toxicity, progression free survival (PFS) and overall survival (OS). METHODS: From March 2004 to October 2014, 341 patients underwent surgery followed by concomitant and adjuvant chemo-radiotherapy. From 2003 to 2010, 167 patients were treated using 3DCRT; starting from 2011, 174 patients underwent VMAT. The quantitative evaluation of the treatment plans was performed by means of standard dose volume histogram analysis. Response was recorded using the Response Assessment in Neuro-Oncology (RANO) criteria and toxicities graded according to Common Terminology Criteria for Adverse Event version 4.0. RESULTS: Both techniques achieved an adequate dose conformity to the target. The median follow up time was 1.3 years; at the last observation 76 patients (23.4 %) were alive and 249 (76.6 %) dead (16 patients were lot to follow-up). For patients who underwent 3DCRT, the median PFS was 0.99 ± 0.07 years (CI95: 0.9-1.1 years); the 1 and 3 years PFS were, 49.6 ± 4 and 19.1 ± 3.1 %. This shall be compared, respectively, to 1.29 ± 0.13 years (CI95: 1.01-1.5 years), 60.8 ± 3.8, and 29.7 ± 4.6 % for patients who underwent VMAT (p = 0.02). The median OS for 3DCRT patients was 1.21 ± 0.09 years (CI95:1.03-1.3 years); 1 and 5 year OS was, 63.3 ± 3.8 and 21.5 ± 3.3 %. The corresponding results for 3DRCT patients were 1.56 ± 0.09 years (CI95:1.37-1.74 years), 73.4 ± 3.5, 30 ± 4.6 % respectively (p < 0.01). In both groups, prognostic factors conditioning PFS and OS were age, gender, KPS, histology and extent of resection (EOR). CONCLUSIONS: VMAT resulted superior to 3DCRT in terms of dosimetric findings and clinical results.

Comorbidity, postoperative morbidity and survival in patients undergoing radical surgery for malignant pleural mesothelioma.

OBJECTIVES: We examined a series of malignant pleural mesothelioma (MPM) patients who underwent radical surgery to explore relationships among comorbidity, postoperative morbidity and survival. METHODS: A retrospective analysis was carried out of all MPM patients operated on in a single centre from 2000 to 2015. The Charlson Comorbidity Index (CCI) was used to classify patients according to their underlying condition. Postoperative complications were scored according to WHO-derived criteria. Survival comparisons were performed by Cox analysis. RESULTS: Ninety-one patients underwent extrapleural pneumonectomy (EPP), 47 underwent pleurectomy decortication (PD) and 25 underwent palliative pleurectomy. The mean CCI of PD patients was significantly higher compared with that of EPP patients (P= 0.044). The frequency of grade 3+ complications was similar between EPP and PD (27 vs 26%). However, EPP patients had a 6-fold higher frequency of pleural sepsis (24 vs 4%, P= 0.002) occurring up to 695 days postoperatively. Median overall survival was 19 months (95% CI 13-25) after EPP, 30 months (95% CI 20-35) after PD and 13 months (95% CI 5-32) after palliative pleurectomy. At multivariate analysis, CCI (P< 0.001), histology (P= 0.014) and pleural sepsis (P= 0.001), but not complete resection, were significantly associated with survival. There was a trend in favour of PD over palliative resection after adjusting for histology and CCI. CONCLUSIONS: The CCI is an independent predictor of survival in MPM patients undergoing radical surgery. Owing to its significant frequency and adverse impact, pleural sepsis may contribute to a reduced life expectancy after EPP. Surgical treatment of MPM remains debatable.

Outcome Evaluation of Oligometastatic Patients Treated with Surgical Resection Followed by Hypofractionated Stereotactic Radiosurgery (HSRS) on the Tumor Bed, for Single, Large Brain Metastases.

PURPOSE: The aim of this study was to evaluate the benefit of a combined treatment, surgery followed by adjuvant hypofractionated stereotactic radiosurgery (HSRS) on the tumor bed, in oligometastatic patients with single, large brain metastasis (BM). METHODS AND MATERIALS: Fom January 2011 to March 2015, 69 patients underwent complete surgical resection followed by HSRS with a total dose of 30Gy in 3 daily fractions. Clinical outcome was evaluated by neurological examination and MRI 2 months after radiotherapy and then every 3 months. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume, and brain distant progression as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Surgical morbidity and radiation-therapy toxicity, local control (LC), brain distant progression (BDP), and overall survival (OS) were evaluated. RESULTS: The median preoperative volume and maximum diameter of BM was 18.5cm3 (range 4.1-64.2cm3) and 3.6cm (range 2.1-5-4cm); the median CTV was 29.0cm3 (range 4.1-203.1cm3) and median PTV was 55.2cm3 (range 17.2-282.9cm3). The median follow-up time was 24 months (range 4-33 months). The 1-and 2-year LC in site of treatment was 100%; the median, 1-and 2-year BDP was 11.9 months, 19.6% and 33.0%; the median, 1-and 2-year OS was 24 months (range 4-33 months), 91.3% and 73.0%. No severe postoperative morbidity or radiation therapy toxicity occurred in our series. CONCLUSIONS: Multimodal approach, surgery followed by HSRS, can be an effective treatment option for selected patients with single, large brain metastases from different solid tumors.

Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection.

BACKGROUND: Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS). METHODS: From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1-3 cm and 32Gy/4 fractions for lesions 3.1-5 cm. Local progression was defined as increase of the enhancing abnormality on MRI, and distant progression as new brain metastases outside the irradiated volume. Toxicity in terms of radio-necrosis was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion- MRI. RESULT: The median maximum diameter of BM was 2.9 cm (range 2.1-5 cm), the median gross target volume (GTV) was 16.3 cm(3) and the median planning target volume (PTV) was 33.7 cm(3) The median,1,2-year local control rate was 30 months, 96, 96 %; the median, 1-2-year rate of BDP was 24 months, 12, 24 %; the median,1,2-year OS was 14 months, 69, 33 %. KPS and controlled extracranial disease were associated with significant survival benefit (p <0.01). Brain radio-necrosis occurred in six patients (5.8 %). CONCLUSION: In patients with single, large BMs unsuitable for surgical resection, HSRT is a safe and feasible treatment, with good brain local control and limited toxicity.