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Purpose: Regorafenib demonstrated encouraging results in recurrent glioblastoma patients. Some studies showed that changes in circulating thyroid hormones (fT3, fT4, fT3/fT4 ratio) can be considered as prognostic factors in patients with various types of tumors. We designed this study to investigate the relationship between baseline thyroid variables and outcome in IDH-wild type GBM patients who were treated with regorafenib., Methods: This multicenter retrospective study included recurrent IDH-wild-type glioblastoma patients treated with regorafenib. Only patients with baseline thyroid function values (TSH, fT3, fT4, fT3/fT4 ratio) available were evaluated. RANO criteria were used to analyze neuroradiological response. Survival curves were estimated using the Kaplan-Meier method. The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4) and survival (PFS, OS) were investigated with Cox regression models., Results: From November 2015 to April 2022, 134 recurrent IDH-wildtype GBM patients were treated with regorafenib and 128 of these had information on baseline thyroid function value. Median follow-up was 8 months (IQR 4.7-14.0). Objective Response Rate was 9% and Disease Control Rate was 40.9%. Median PFS was 2.7 months (95%CI 2.2-3.6) and median OS was 10.0 months (95%CI 7.0-13.0). Lower baseline TSH value in the blood was correlated with a higher rate of disease progression to regorafenib (p = 0.04). Multivariable analyses suggested a non-linear relationship between PFS (p = 0.01) and OS (p = 0.03) with baseline fT3/fT4 ratio., Conclusion: In recurrent wild-type IDH glioblastoma patients, baseline fT3/fT4 ratio showed a non-linear relationship with survival, with different impacts across the spectrum of fT3/fT4 ratio. Moreover, baseline TSH may be a predictor of regorafenib activity., (© 2023. The Author(s).)

Since the first definition by Hellman and Weichselbaum in 1995, the concept of OligoMetastatic Disease (OMD) is a growing oncology field. It was hypothesized that OMD is a clinical temporal window between localized primary tumor and widespread metastases deserving of potentially curative treatment. In real-world clinical practice, OMD is a "spectrum of disease" that includes a highly heterogeneous population of patients with different prognosis. Metastasis directed therapy with local ablative treatment have proved to be a valid alternative to surgical approach. Stereotactic body radiation therapy demonstrated high local control rate and increased survival outcomes in this setting with a low rate of toxicity. However, there is a lack of consensus regarding many clinical, therapeutic, and prognostic aspects of this disease entity. In this review, we try to summarize the major critical features that could drive radiation oncologists toward a better selection of patients, treatments, and study endpoints. With the help of a set of practical questions, we aim to integrate the literature discussion., (© 2022. The Author(s).)

Circulating tumor cells detection and ARV7 expression are associated with worse clinical outcomes in metastatic Castration-Resistant Prostate Cancer (mCRPC) undergoing Androgen Receptor Targeted Agents. ARFL, PSMA and PSA may help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCPRC undergoing I line ARTA therapy terminated the planned enrollment in 2020. Here, we present a pre-planned interim analysis with 18 months of median follow-up. RT-qPCR was used to determine the CTC expression of PSA, PSMA, AR and ARV7 before starting ARTA. PSA-drop, Progression-Free and Overall Survival (PFS and OS) and their correlation with CTC detection were reported. Forty-four patients were included. CTC were detected in 43.2% of patients, of whom 8.94% expressed PSA, 15.78% showed ARV7, 63.15% and 73.68% displayed ARFL and PSMA, respectively. Biochemical response was significantly improved in CTC + vs CTC- patients, with median PSA-drop of 18.5 vs 2.5 ng/ml (p = 0.03). After a median follow-up of 18 months, 50% of patients progressed. PFS was significantly longer in CTC- patients (NR vs 16 months). Eight (18.2%) patients died, a non-significant trend in terms of OS was detected in favor of CTC- patients (NR vs 29 months, p = 0.05). AR, PSA and PSMA expression in CTC + had no significant impact on PSA-drop, PFS or OS. PRIMERA-trial confirmed the CTC detection predictive importance in mCRPC patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aromatase Inhibitors (AIs) are recommended for the adjuvant treatment of hormone receptor positive breast cancer in both high-risk pre-menopausal and post-menopausal population; arthralgia is the main cause of discontinuation of therapy and affects up to 25% of population on AI treatment. The objective of the study was to prospectively evaluate OPERA® (GAMFARMA srl, Milan, Italy), a new dietary supplement where α-Lipoic acid, Boswellia serrata, Methylsulfonylmethane and Bromelain are combined in a single hard-gelatin capsule to be taken once a day. Fifty-three patients with arthralgia (NCI-CTCAE v4.0 grade ≥ 1) occurring during AI therapy were enrolled. All patients received OPERA® from enrollment (T0) up to sixth months (T3). Patients' AI-related arthralgia was evaluated every two months with VAS Scale, PRAI questionnaire, and CTCAE scale. Primary endpoint was the number of patients with symptom resolution (G0) at T3 if compared to T0, according to CTCAE and VAS scale. Secondary endpoints were decrease in arthralgia intensity measured with PRAI score at T3 compared to baseline, safety of OPERA® and rate of AI interruption. Treatment with OPERA® supplement was overall well tolerated; no relevant toxicities related to OPERA® intake were reported. Seven subjects (13.2%) were not included in the final analysis because of consent withdrawal. 46 participants were eligible for final analysis. According to CTCAE scale, 10 out of 46 patients reported symptoms resolution at 6-month follow-up from the time of enrollment T0 (p = 0.0009). According to VAS score, 5 patients reported complete resolution of symptoms at T3 if compared to baseline starting situation T0 (p = 0.0222). Analysis of PRAI score showed a significant reduction in arthralgia-related pain perceived (p = 0.0001). OPERA® was able to reduce the intensity of arthralgia related to AI therapy. Randomized, double-blind studies are warranted to confirm the effectiveness of this dietary supplement., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to investigate how different patterns of GBM failure influence second surgery outcomes. Overall survival (OS) and post-recurrence survival (PRS) were assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves. Patients with local recurrence had better OS than patients with non-local one, 24.1 versus 18.2 months, respectively [P = 0.015, HR = 1.856 (1.130-3.050)]. The second surgery conferred an advantage in OS respect to non-operated patients, however, this advantage was more evident in patients with local recurrence [P = 0.002 with HR 0.212 (95% CI 0.081-0.552) and P = 0.029 with HR = 0.522 (95% CI 0.291-0.936), respectively]. The recurrence pattern can influence the outcome of patients with recurrent GBM suitable for a second surgery., (© 2021. Belgian Neurological Society.)

Non-surgical locally ablative treatments for primary liver cancer and liver metastases represent an effective therapeutic choice when surgery cannot be performed or is not indicated. Thermal ablative employing electric currents or electromagnetic fields have historically played an important role in this setting. Radiotherapy, in the last decades, due to a series of important technological development, has become an attractive option for the treatment of liver tumours, especially with the introduction of Stereotactic Body Radiotherapy. Published literature so far evidenced both for radiotherapy and thermal ablative techniques a benefit in terms of local control and other oncological outcomes; however, no direct prospective comparison between the two techniques have been published so far. The aim of this review is to summarize the technical and clinical implications of these treatment modalities and to identify criteria to allocate patients to one or another option in consideration of the expected efficacy. The main features and critical aspects of both thermoablative techniques and external beam radiation will also be covered in the present paper.

Recent advances in computing capability allowed the development of sophisticated predictive models to assess complex relationships within observational data, described as Artificial Intelligence. Medicine is one of the several fields of application and Radiation oncology could benefit from these approaches, particularly in patients' medical records, imaging, baseline pathology, planning or instrumental data. Artificial Intelligence systems could simplify many steps of the complex workflow of radiotherapy such as segmentation, planning or delivery. However, Artificial Intelligence could be considered as a "black box" in which human operator may only understand input and output predictions and its application to the clinical practice remains a challenge. The low transparency of the overall system is questionable from manifold points of view (ethical included). Given the complexity of this issue, we collected the basic definitions to help the clinician to understand current literature, and overviewed experiences regarding implementation of AI within radiotherapy clinical workflow, aiming to describe this field from the clinician perspective.

Introduction: The immune checkpoint inhibitors (ICPIs) agents anti-T lymphocytes-associated antigen 4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) and its ligands (PD-L1/PD-L2) have opened a new scenario in the treatment of cancer. These agents can induce immuno-related adverse events (irAEs), which may affect the endocrine system., Purpose: The aim of this study was to analyze the occurrence and the course of endocrine irAEs in cancer patients treated with anti-PD-1 immunotherapy., Methods: This was a retrospective, multicentre study, involving cancer patients treated with the PD-1 inhibitors nivolumab or pembrolizumab at reference Oncology Centres. One hundred and seventy-nine consecutive patients with different types of cancer (mostly non-small cell lung cancer, melanoma, kidney cancer) were included in the study. Patients had received nivolumab (70.9%) or pembrolizumab (29.1%) for 2-33 months. The study evaluated clinical data records until the established date of July 15, 2018. The primary end point was the assessment of endocrine toxicity and possible predictive factors., Results: Endocrine toxicity occurred in 54 out of 179 patients (30.2%) and was related to thyroid dysfunction, with the exception of one case of diabetes mellitus. Thyroid toxicity occurred mostly within 2 months from the initiation of immunotherapy (83% of cases). A pre-existing thyroid dysfunction was a significant predictor of disease flare., Conclusions: Thyroid alterations are frequently associated with anti PD-1 treatment in cancer patients. Regular thyroid assessment should be performed, particularly in the first months of treatment and in patients with a pre-existing thyroid disease.

Both endocrine and chemotherapy can be utilized for breast cancer patients' management, in multiple setting (i.e., primary systemic therapy, adjuvant, metastatic treatment). Health-related quality of life in breast cancer survivors can be significantly influenced by cognitive impairment, which has been related in several previously reported experiences to systemic therapies administration. However, although the growing body of literature, the impact of both chemo- and endocrine therapy on cognitive function is currently unclear, due to many confounding factors (i.e., multiple therapies, duration of therapy, comorbidity, age). The aim of the present review is to present an overview of the current literature concerning the possible influence of endocrine and systemic therapy on breast cancer patients' cognitive impairment.

Over the years, thanks to the addition of new generation systemic agents, as well as the use of more advanced and precise radiotherapy techniques, it was able to obtain a high curability rate for breast cancer. Anthracyclines play a key role in the treatment of breast disease, with a well-known benefit on disease-free survival of patients with positive nodal status. Trastuzumab have shown a significant outcome advantage after 1-year administration in case of HER2-positive disease. Unfortunately, significant increase in cardiotoxicity has been observed after anthracyclines and trastuzumab therapies. Even though the cardiology and oncology community strongly recommend a cardiotoxicity prevention strategy for this subset of patients, there is still no consensus on the optimal patient's approach. We aimed to review the published and ongoing researches on cardioprevention strategies and to present the SAFE trial (CT registry ID: NCT2236806; EudraCT number: 2015-000914-23). It is a randomized phase 3, four-arm, single-blind, placebo-controlled study that aims to evaluate the effect of bisoprolol, ramipril or both drugs, compared to placebo, on subclinical heart damage evaluated by speckle tracking cardiac ultrasound in non-metastatic breast cancer patients.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA ® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA ® supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA ® . Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA ® was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients' population is warranted to confirm its promising activity.

The aim of our analysis was to report the outcome and safety of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2-negative metastatic breast cancer. Between February 2009 and August 2011, 62 consecutive patients received paclitaxel 90 mg/m(2) on days 1, 8, and 15 and bevacizumab (BV) 10 mg/kg intravenously on days 1 and 15, every 28-day cycle. After 6 cycles of combined treatment, patients were given maintenance BV every 3 weeks (15 mg/kg) until progression disease or unacceptable toxicity. At time of analysis, median overall survival was 12.3 months (range 4.6-44.8 months), progression-free survival was 8.1 months (range 2.3-33.2 months), and time to treatment failure was 8.4 months (range 2.3-33.2 months). Our results confirmed the efficacy and the acceptable toxicity profile of bevacizumab plus paclitaxel as first-line regimen for metastatic breast cancer.