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Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19–positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.

Background: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. Methods: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. Results: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. Conclusion: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

Background: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. Methods: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. Results: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. Conclusion: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

Background: Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25 Gy in 5 daily fractions. Methods: Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis. Discussion: This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas.

Radiotherapy is a pivotal treatment for treating breast cancer. However, its role in the management of elderly patients is still under debate. Some authors suggest be avoided after surgery for early stage, some others advocate its adoption. For breast cancer treatment different schedules are used both for whole and partial breast irradiation, in adjuvant as well as definitive setting. Which one is better for elderly patients is a controversial topic. Numerous studies focused on both moderate or extreme hypofractionated irradiation have been published. However, only few addressed the topic on elderly patient population. The data on hypofractionated radiotherapy showed that for whole breast, locoregional and post-mastectomy treatment, this approach is a valid option reporting similar efficacy and toxicity to the standard fractionation. Also accelerated partial breast irradiation for patients with favourable early stage disease represents a viable option allowing for de-escalation by targeting radiation dose to the part of breast tissue at highest recurrence risk. Undoubtedly, for frail and elderly patients a short course of radiotherapy could increase their adherence and the quality of life. In the same manner, the preoperative approach has been applied for both whole and partial breast irradiation, allowing for more precise target delineation compared to the post-surgical one, eventually leading to a smaller treatment volume, to less geographical missing and possibly to a lower radiation-induced toxicity. Some more long-term results could make us more confident in prescribing adjuvant or preoperative partial breast irradiation. These approaches could be the most appropriate treatment for elderly patients, potentially preserving quality of life and increasing the tolerability to the irradiation.

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

Background: Italy experienced one of the world’s severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery. Materials and methods: A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after. Results: All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients. Conclusion: The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments.

Radiotherapy is a pivotal treatment for treating breast cancer. However, its role in the management of elderly patients is still under debate. Some authors suggest be avoided after surgery for early stage, some others advocate its adoption. For breast cancer treatment different schedules are used both for whole and partial breast irradiation, in adjuvant as well as definitive setting. Which one is better for elderly patients is a controversial topic. Numerous studies focused on both moderate or extreme hypofractionated irradiation have been published. However, only few addressed the topic on elderly patient population. The data on hypofractionated radiotherapy showed that for whole breast, locoregional and post-mastectomy treatment, this approach is a valid option reporting similar efficacy and toxicity to the standard fractionation. Also accelerated partial breast irradiation for patients with favourable early stage disease represents a viable option allowing for de-escalation by targeting radiation dose to the part of breast tissue at highest recurrence risk. Undoubtedly, for frail and elderly patients a short course of radiotherapy could increase their adherence and the quality of life. In the same manner, the preoperative approach has been applied for both whole and partial breast irradiation, allowing for more precise target delineation compared to the post-surgical one, eventually leading to a smaller treatment volume, to less geographical missing and possibly to a lower radiation-induced toxicity. Some more long-term results could make us more confident in prescribing adjuvant or preoperative partial breast irradiation. These approaches could be the most appropriate treatment for elderly patients, potentially preserving quality of life and increasing the tolerability to the irradiation.

Background: Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25 Gy in 5 daily fractions. Methods: Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis. Discussion: This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas.

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

Background: Italy experienced one of the world’s severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery. Materials and methods: A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after. Results: All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients. Conclusion: The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments.

Treatment options for intracranial meningiomas are surgical resection alone, surgery followed by adjuvant radiation therapy (RT), or exclusive RT. Parasagittal and parafalcine meningiomas are a subgroup of meningeal disease located close to the vascular structures. Considering the frequent venous invasion, a complete resection is not possible in the majority of cases, and even if a Simpson Grade I resection can be performed, the risk of recurrence is relevant. To date, few studies are focused on parasagittal and parafalcine meningiomas. Because of their specific related issues, particular considerations on decision-making process, outcome, and toxicity follow-up are mandatory. In fact, parasagittal and parafalcine meningiomas require a clear-cut radiological assessment, as well as a tailored toxicity risk evaluation. Moreover, similarly to other meningioma sites, also for parasagittal and parafalcine ones, a standardization of local control, toxicity, and quality of life evaluation is needed in order to lead to a pooled analysis of the results. In this context, our aim was to review the literature data regarding the role of both single-session and multisession radiosurgery (RS), and stereotactic radiotherapy (SRT) for parasagittal and parafalcine meningioma management, summarizing available data on safety and efficacy. It was also discussed how RS and SRT can be performed in a setting of evolving views concerning the treatment paradigm of the parasagittal and parafalcine meningiomas.

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.

Background: Meningioma are the second most common brain tumors in adults and can cause significant morbidity and mortality. The scarcity of in vitro and in vivo models represents the major obstacle to understand the molecular basis of meningioma tumorigenesis. The main aim of this study was to assess a method for radiobiology of meningioma cells colture by means of well-known meningioma lines. New method: We carried out a protocol of cells culture for irradiation of meningioma cells. We used the immortalized cell lines IOMM-Lee and CH-157 to study their radiation-reponse by means of clonogenic assays and to evaluate their proliferation and apoptosis. We irradiated the cells with different total doses using two different linear accelerators. Results: We observed a more radiation resistance of the IOMM-Lee than the CH-157. Indeed, the cellular death of CH-157 was obtained at a very low dose irradiation. Moreover, we showed a dose-response effect due to the early and late apoptosis, in fact the rate of apoptotic cells is greater than that of the necrotic cells at any dose of irradiation and at any time of analysis. Comparison with existing methods: There is not a standardized method for radiobiology of meningioma experiments. Conclusions: Our method of cells culture appears suitable for radiosensitivity studies on meningioma. We can confirm that the response to radiotherapy depends not only on irradiation features, but also on tumor radiosensitivity.

The trigeminal neuralgia (TN) is a chronic, episodic, and disabling facial pain syndrome. It is a relatively rare disorder. Despite this, because of the intensity of the pain, TN may have a dramatic impact for many patients. Fortunately, most of the patients may obtain a good pain relief simply by taking drugs. Historically, the surgical approaches represent a true treatment paradigm for all the drug-resistant TN. In this context, radiosurgery (RS) is a relatively new treatment modality. The effectiveness and safety of radiosurgery are today widely accepted and the technique can be proposed to many patients which suffer from a drug-resistant TN. This is true especially when the patients are less than ideal candidates for an open surgery, or for elderly ones, when a clear neuro-vascular conflict is not evident. The present review provides a concise analysis of the actual indications for radiosurgery, as well as the most acknowledged prognostic factors. The pathogenesis of TN and the rationale for the RS efficacy are also investigated and described. Some technical aspects including the target selection and the prescription doses, which have widely changed in time, are depicted. In conclusion, the present review supports the idea that TN is a complex disease and radiosurgery represents an effective and relatively new treatment modality, which enriches the treatment armamentarium for these unfortunate patients. To optimize the RS results, a correct patient selection has to be performed.

Purpose: Most recent literature has confirmed the efficacy of single-session radiosurgery (sRS) in the treatment of intracranial meningioma. Unfortunately, sRS is not always applicable due to large tumor volume and the proximity of the tumor to critical structures. When sRS is not recommended, multi-session radiosurgery (mRS) can be the solution. The best treatment schedule for mRS, however, is not well established. The aim of the present retrospective study is to validate the effectiveness of one approach, 25 Gy delivered in 5 fractions in 5 consecutive days, to treat skull base meningiomas. Methods: This is a retrospective multicenter study. Patients with an anterior or a medium skull base meningioma that could not be treated by sRS due to large volume or proximity to the anterior optic pathways (AOPs) underwent 5-fraction mRS. Only patients with at least 36 months follow-up were included in the analysis. Local control and visual outcomes were investigated. Results: One-hundred-sixty-seven patients were included in the analysis. One-hundred-one patients underwent RS as a primary indication and 66 were treated after a previous surgery. The median follow-up period was 51 months (range 36–129 months). Progression-free survival at 3, 5 and 8 years were, respectively, 98%, 94% and 90%. Excluding the progressive disease patients, the visual worsening rate was 3.7%. The 42% of the patients with a pre-treatment visual deficit experienced improvement in vision. Conclusion: 25 Gy delivered in 5 fractions is an effective modality for meningiomas that are near the AOP or are too large to be treated by sRS. The treatment schedule controlled the tumors while sparing visual function.

Treatment options for intracranial meningiomas are surgical resection alone, surgery followed by adjuvant radiation therapy (RT), or exclusive RT. Parasagittal and parafalcine meningiomas are a subgroup of meningeal disease located close to the vascular structures. Considering the frequent venous invasion, a complete resection is not possible in the majority of cases, and even if a Simpson Grade I resection can be performed, the risk of recurrence is relevant. To date, few studies are focused on parasagittal and parafalcine meningiomas. Because of their specific related issues, particular considerations on decision-making process, outcome, and toxicity follow-up are mandatory. In fact, parasagittal and parafalcine meningiomas require a clear-cut radiological assessment, as well as a tailored toxicity risk evaluation. Moreover, similarly to other meningioma sites, also for parasagittal and parafalcine ones, a standardization of local control, toxicity, and quality of life evaluation is needed in order to lead to a pooled analysis of the results. In this context, our aim was to review the literature data regarding the role of both single-session and multisession radiosurgery (RS), and stereotactic radiotherapy (SRT) for parasagittal and parafalcine meningioma management, summarizing available data on safety and efficacy. It was also discussed how RS and SRT can be performed in a setting of evolving views concerning the treatment paradigm of the parasagittal and parafalcine meningiomas.

Background: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer. Methods: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result. Results: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer. Conclusions: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results.

Background: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer. Methods: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result. Results: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer. Conclusions: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results.

Purpose: Meningiomas account for one third of primary intracranial tumors; nevertheless information on meningioma cell lines and in vivo models is scant. Although radiotherapy is one of the most relevant therapeutic options for the treatment of patients with meningioma, radiobiological research to understand tumor response to this treatment is far from being thoroughly figured out. The aim of this report is to provide a comprehensive picture of the current literature on this field, so as to foster research in this regard. Methods: We carried out a review of meningioma radiobiology based on a peer-reviewed PubMed search. Results: Our findings confirm that the main limitation of radiobiological research into meningioma is the paucity of robust in vitro and in vivo models. Alternative approaches to overcome the already identified problems, and to allow better understanding of the entire histopathological spectrum of meningiomas have been explored. Conclusions: A radiobiological perspective of meningioma may help to improve clinical results both in terms of tumor control and healthy tissue sparing. Although we are far from drawing any conclusions, this review can lead researchers to identify some clues for future areas of study.

Background Paragangliomas are highly vascular and predominantly benign neoplasms that traditionally have been treated by surgery, embolization, and/or external beam radiotherapy. The aim of this study was to evaluate long-term local tumor control and the safety of radiosurgery for head and neck paragangliomas. Methods Data were obtained from prospectively maintained databases of patients affected by brain tumors treated with radiosurgery at our institution. The inclusion criteria were histologically proven or radiologic-suspected diagnosis of paragangliomas; a follow-up period of at least 12 months, an magnetic resonance imaging–based tumor growth control analysis and a signed written consent. Twenty patients (21 paragangliomas) met the eligibility criteria and were included in the present study. All patients were clinically and radiologically evaluated before and after treatment. Results The mean follow-up at the time of the present analysis was 46 months. Seven patients had a follow-up longer than 60 months. Seven lesions underwent a single-session radiosurgery with a mean dose of 12.2 Gy (range 11–13 Gy). Fourteen lesions underwent multisession radiosurgery with a mean dose of 25.7 Gy (range 20–30 Gy) delivered in 3–5 fractions. The mean tumor volume for single-session radiosurgery was 4 cc (range 1.4–9.2). The mean volume for multisession radiosurgery was 18.9 cc (range 1.3–50.9). None of the lesions showed progression on radiology during the follow-up period. Neurologic conditions generally are maintained or improved. Conclusions Both single and multisession radiosurgery were confirmed as a safe and effective treatment modality for paragangliomas. Multisession radiosurgery appears effective to treat large lesions.

Purpose: Despite recent advances, the prognosis of glioblastoma (GBM) remains poor. The aim of this study was to assess the efficacy and tolerability of multiple daily fraction radiotherapy performed with multiple temozolomide (TMZ) administrations in newly diagnosed patients with GBM. Methods: This trial was a prospective, open-label, monocentric, nonrandomized, single arm, phase II study. The primary endpoint was the proportion of progression-free patients at 12 months, and the secondary endpoints were overall survival (OS) and toxicity. Thirty-five patients underwent two radiotherapy courses concomitant with TMZ after surgery. At each course, radiation was delivered 3 times daily, 2 Gy/fraction, for 5 consecutive days, and the total dose was 60 Gy; concurrent TMZ was administered in a total dose of 150-200 mg/m2/day. Results: The primary endpoint failed to be applied; Macdonald criteria could be used in 16 (46%) patients with local or intracerebral recurrence (group A). In 12 patients, due to suspicion of radiation necrosis vs recurrence, Macdonald criteria were not applied (group B). The OS was 22 months, and OS probabilities at 12, 18, and 24 months were 82%, 59%, and 44%, respectively. Hematologic toxicities generally did not exceed grade 2. The quality of life and cognitive functioning did not significantly change between baseline and the first follow-up. In the multivariate analysis, necrosis and pseudoprogression were significant prognostic factors of OS. Conclusions: To improve local control and OS, a more aggressive treatment schedule should be explored. The related higher necrosis risk and its implications regarding local control deserve further investigation.

Background Radiosurgery(RS), both in single and multiple sessions, have been performed for intracranial meningiomas. Different aspects are still controversial on this field. The aim of this systematic review is to summarize the current literature on long-term efficacy and safety of RS for meningiomas. Methods Online databases were searched for studies published until April 2015. The primary outcomes were disease control and progression-free-survival(PFS). The secondary outcomes were symptom control and radiation-induced toxicity. Results The estimate of disease control rate ranged from 87.0% to 100.0% at 5 years and from 67.0% to 100.0% at 10 years. The PFS rate ranged 78.0%–98.9% and 53.1%–97.2% at 5 and 10 years, respectively. The overall symptom control was 92.3%, the overall toxicity was 8.1%. Conclusions RS can be considered a safe and effective treatment. Efforts are needed in standardizing the definition of local and symptom control and toxicity in order to properly compare different treatment schedules.

Background: A new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy. Methods/Design: To investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction-diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction-diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario. Our results show that patient survival could be significantly improved by this combined treatment modality. Discussion: High priority should be given to experiments to validate the therapeutic benefit predicted by our model.

Background: A new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy. Methods/Design: To investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction-diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction-diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario. Our results show that patient survival could be significantly improved by this combined treatment modality. Discussion: High priority should be given to experiments to validate the therapeutic benefit predicted by our model.

Background/aim: Meningiomas of the anterior cranial fossa are often diagnosed after impaired visual function occurrence. Some epidemiologic studies suggest an association between exogenous or endogenous hormones and meningioma risk. The aim of this study is to briefly review the literature and relate a case report.Patient and methods: This study presents a case of a 51-year-old woman with a moderate visual loss of 6/10 and markedly constricted visual field in the right eye. A normal visual acuity and peripheral reduction of visual field in the left eye was documented. During medical interview, she reported a prolonged assumption of oral contraceptive. Her visual deterioration had progressed over the previous 3 months and was associated with occasional headache. MRI scanning showed a small optic pathway meningioma.Results: After various examinations, it was decided to wait and see and no therapy was administered. The patient noticed a progressive improvement in the vision in her right eye, with corresponding improvement in the bilateral visual field.Conclusion: The case reports on the spontaneous resolution of visual loss due to the volume reduction of the anterior visual pathway compressive intracranial meningioma after interruption of prolonged assumption of oral contraceptive and focuses on the correlation between sexual hormone pathway and intracranial meningioma.

BACKGROUND: Concern about radiation-induced optic neuropathy (RION) has governed recent thinking about the role of radiation therapy in the treatment of meningiomas involving the anterior optic pathways. Despite this concern, during the last few years, the use of radiosurgery for such lesions has increased steadily. OBJECTIVE: To define both the tumor control rate and the risk of RION over a long-term follow-up period in a large cohort of patients treated with multisession radiosurgery. METHODS: The local control and visual outcome of 143 patients who underwent multisession radiosurgery (mRS) were evaluated. Neurological outcome was also analyzed. The data for the present study were obtained from a prospectively maintained database. RESULTS: The mean follow-up was 44 months (range, 12-113 months). All patients underwent mRS. The median prescription dose was 25 Gy delivered in 3 to 5 fractions. The prescription isodose, which typically encompassed at least 95% of the tumor, ranged from 65% to 86% (median, 80%). The mean tumor volume was 11.0 cm 3 (range, 0.1-126.3 cm 3; median, 8 cm 3). The progression-free survival at 3, 5, and 8 years was 100%, 93%, and 90%, respectively. Compared with baseline, visual function improved in 36% of patients, whereas 7.4% experienced a worsening in visual function (5.1% excluding the patients with progressive disease). CONCLUSION: Good local control rate and a low risk of RION indicate that mRS is a safe and effective treatment option in cases of large meningiomas. ABBREVIATIONS: AOP, anterior optic pathway AVP, anterior visual pathway mRS, multisession radiosurgery PD, progressive disease RION, radiation-induced optic neuropathy sRS, stereotactic radiosurgery.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife® SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan–Meier method. Median follow-up was 9 months (range 15 days–82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife® SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan–Meier method. Median follow-up was 9 months (range 15 days–82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit.

In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage. Evidence of immune response and interaction with chemotherapy were investigated. After a median follow up of 17.4 months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC vaccination induced a significant, persistent activation of NK cells, whose increased response was significantly associated with prolonged survival. CD8+T cells underwent rapid expansion and priming but, after the first administration of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was associated with robust expression of the multidrug resistance protein ABCC3 in NK but not CD8+T cells. The negative effect of TMZ on the formation of T cell-associated antitumor memory deserves consideration in future clinical trials including immunotherapy

Background: The incidence of glioblastoma (GBM) in the elderly population is currently increasing, with a peak seen between 65 and 84 years. The optimal treatment in terms of both efficacy and quality of life still remains a relevant and debated issue today. The purpose of our study was to evaluate the feasibility of short-course hypofractionated accelerated radiotherapy (HART) in GBM patients aged over 70 years and with a good Karnofsky performance score (KPS). Methods: A review of medical records at the "Istituto Neurologico C. Besta" was undertaken; patients aged ≥ 70 years who had undergone adjuvant HART for GBM between January 2000 and January 2004 were included in the study. HART was administered to a total dose of 45 Gy, 2.5 Gy/fraction, in three daily fractions for three consecutive days/cycle fractions each, delivered in two cycles (split 15 days). Results: A total of 33 patients were evaluable for the current analysis. Median follow-up was 10 months. According to CTCAE (version 3.0) criteria, none of the patients developed radiation-induced neurological status deterioration or necrosis. KPS evaluation after HART was found to be stable in 73 % of patients, improved in 24 %, and worse in 3 %. The median overall survival time of the entire study population was 8 months (range 2-24). Conclusions: Our findings suggest that a hypofractionated accelerated schedule can be a safe and effective option in the treatment of GBM in the elderly. © 2013 Urban & Vogel

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997-2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years. Progression-free survival was 15% at 1 year. Prolongation of survival was significantly associated with surgery in patients with a good performance status, whatever the patient's age, with an adjusted hazard ratio of 0.55 (p < 0.001) or a 45% relative decrease in the risk of death. Radiotherapy and chemotherapy improved survival, with adjusted hazard ratios of 0.61 (p = 0.001) and 0.89 (p = 0.04), respectively, regardless of age, performance status, or residual tumor volume. Recurrence occurred in 99% of patients throughout the follow-up. Reoperation was performed in one-fourth of these patients but was not effective, whether performed within 9 months (hazard ratio, 0.86; p = 0.256) or after 9 months (hazard ratio, 0.98; p = 0.860) of initial surgery, whereas second-line chemotherapy with procarbazine, lomustine, and vincristine (PCV) or with temozolomide improved survival (hazard ratio, 0.77; p = 0.008). Surgery followed by radiotherapy and chemotherapy should be considered in all patients with glioblastoma, and these treatments should not be withheld because of increasing age alone. The benefit of second surgery at recurrence is uncertain, and new trials are needed to assess its effectiveness. Chemotherapy with PCV or temozolomide seems to be a reasonable option at tumor recurrence.