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Abstract   Objectives The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. Patients and methods Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) ≥ 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150–200 mg/m2 for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life. Results The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3–4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time. Conclusions Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract   Objectives The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. Patients and Methods 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m2 per day followed by six cycles of adjuvant temozolomide (150–200 mg/m2 for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. Results The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3–4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. Conclusions Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors. [ABSTRACT FROM AUTHOR]

Opioid-induced constipation (OIC) is a very common and troublesome gastrointestinal side effect following the use of opioids. Despite existing international guidelines, OIC is largely underdiagnosed and undertreated. ECHO OIC is a European project designed to improve the diagnosis and management of OIC at the primary care level. The next phase of the ECHO OIC project is to review and adapt the proposed European pathway at national level, considering the local patient journey and clinical practice. A multidisciplinary group of 12 Italian experts reviewed and discussed the European path and formulated a seven-step guide for the practical management of OIC that is also easily applicable in primary care: 1. When prescribing long-term opioids, the physician should inform the patient of the possibility of the onset of OIC; 2. At opioid prescription, doctors should also prescribe a treatment for constipation, preferably macrogol or stimulant laxatives; 3. The patient should be evaluated for OIC within the second week of initiating opioid treatment, by clinical history and Rome IV criteria; 4. In the presence of constipation despite laxatives, prescription of a PAMORA (Peripherally Acting Mu Opioid Receptor Antagonist) should be considered; 5. When prescribing a PAMORA, prescribing information should be carefully reviewed, and patients should be accurately instructed for appropriate use; 6. Efficacy and tolerability of the PAMORA should be monitored regularly by Bowel Function Index, considering a cut-off of 30 for the possible step-up of OIC treatment; 7. After 4 weeks of treatment, if the efficacy of PAMORA is deemed inadequate, discontinuation of the PAMORA, addition of an anti-constipation drugs, change of opioid type, or referral to a specialist should be considered. Spreading knowledge about the OIC problem as much as possible to the health community is crucial to obtain not only an early treatment of the condition but also to promote its prevention.

Purpose: Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ)., Methods: Italian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated., Results: Answers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered., Conclusion: Italian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules., (© 2024. The Author(s).)

Purpose: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation., Methods: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis., Results: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01)., Conclusions: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients., (© 2023. The Author(s).)

Background: The immune profile of each patient could be considered as a portrait of the fitness of his/her own immune system. The predictive role of the immune profile in immune-related toxicities (irAEs) development and tumour response to treatment was investigated., Methods: A prospective, multicenter study evaluating, through a multiplex assay, the soluble immune profile at the baseline of 53 patients with advanced cancer, treated with immunotherapy as single agent was performed. Four connectivity heat maps and networks were obtained by calculating the Spearman correlation coefficients for each group: responder patients who developed cumulative toxicity (R-T), responders who did not develop cumulative toxicity (R-NT), non-responders who developed cumulative toxicity (NR-T), non-responders who did not develop cumulative toxicity (NR-NT)., Results: A statistically significant up-regulation of IL-17A, sCTLA4, sCD80, I-CAM-1, sP-Selectin and sEselectin in NR-T was detected. A clear loss of connectivity of most of the soluble immune checkpoints and cytokines characterized the immune profile of patients with toxicity, while an inversion of the correlation for ICAM-1 and sP-selectin was observed in NR-T. Four connectivity networks were built for each group. The highest number of connections characterized the NR-T., Conclusions: A connectivity network of immune dysregulation was defined for each subgroup of patients, regardless of tumor type. In patients with the worst prognosis (NR-T) the peculiar connectivity model could facilitate their early and timely identification, as well as the design of a personalized treatment approach to improve outcomes or prevent irAEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mezi, Pomati, Fiscon, Amirhassankhani, Zizzari, Napoletano, Rughetti, Rossi, Schinzari, Tortora, Lanzetta, D’Amati, Nuti, Santini and Botticelli.)

Therapeutic intervention for prostate cancer mostly relies on eliminating circulating androgen or antagonizing its effect at the cellular level. As the use of endocrine therapies grows, an under-reported incidence of cardiovascular toxicities occurs in prostate cancer patients. In this review, we summarize data of clinical studies, investigating the cardiovascular and metabolic alterations associated with the use of old and new endocrine drugs (gonadotropin-releasing hormone [GnRH] agonists and antagonists, androgen receptor inhibitors, 17α-hydroxylase/c-17,20-lyase [CYP17] inhibitor) in prostate cancer. To date, studies looking for links between cardiovascular complications and hormone-mediated therapies in prostate cancer have reached conflicting results. Several confounding factors, such as age of patients and related cardiovascular liability, other comorbidities, and use of concomitant drugs, have to be carefully evaluated in future clinical trials. Further research is needed given the continuous advancements being made in prostate cancer treatment., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS., Patients and Methods: One hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity., Results: Sixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02)., Conclusions: Postoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Malignant gliomas (MG) are aggressive brain tumours in adults. The standard of care is concurrent radiation plus temozolomide (TMZ) [chemo-radiotherapy (CRT)] followed by TMZ maintenance up to 6 months. TMZ is considered to have a low toxicity profile, but several studies reported occurrence of severe myelosuppression, especially during the concomitant phase. Toxicity may be prolonged, thus treatment should be discontinued., Purpose: To evaluate the risk of recurrente myelotoxicity during adjuvant chemotherapy (CT) in patients who recovered from severe myelotoxicity during CRT., Methods: We retrospectively collected data on patients with MG who developed and recovered from severe myelotoxicity during CRT from eight Italian neuro-oncology centers., Results: We included 87 patients. Histology was Glioblastoma (GBM) in 78 patients (89.7%); 60% of patients were female. After myelotoxicity recovery, 54 (62%) received treatment. The majority of them (82%, n = 44) received adjuvant TMZ and 18% (n = 10) others treatments. Out of 44 patients who received adjuvant TMZ, 34% experienced the re-occurrence of grade 3-4 myelotoxicity which required permanent CT discontinuation in 6 (13%) cases. Patients who received TMZ or other treatments had longer overall (OS) (adjusted HR 0.46, p = 0.008) and progression free survival (PFS) (adjusted HR 0.57, p = 0.034) than those who remained untreated., Conclusion: Our study suggests that after severe myelotoxicity the majority of patients received treatment, particularly with TMZ. Only a fraction of patients experienced toxicity recurrence, suggesting that TMZ is well tolerated and had an impact on PFS and OS., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Oncological patients increasingly require second medical opinions to feel more likely confident with their oncologists and treatments, although this could lead to wrong opinions and delay in the start of treatments. Second opinions can be required also by physicians to obtain advices, especially in case of rare tumors. The request of new opinions is documented in radiology and pathology settings too, with not negligible discrepancy rate. Conversely, the role in general medical/surgical conditions has not been well established. Literature is poor of studies relative to second opinions or they are more focused on patient's motivations. For these reasons, AIOM (Italian Association of Medical Oncology) and AIOM Foundation faced this topic during the 7th Annual Meeting on Ethics in Oncology (Ragusa, 4-5 t h May 2018). In this position paper we report reasons, limits, advantages and outcomes of second medical opinion and the respective Decalogue in the oncological setting., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities., Methods: This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival., Results: One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn't (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37-2.09, p < 0.0001; median OS, 4 months vs. 35 months, HR 1.60, 95% CI 1.26-2.02, p < 0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥ 1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden., Discussion: Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well., Conclusions: A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.

Aim: The aim of this study was to compare patients' global impression (PGI) and the achievement of personalised symptom goal response (PSGR), after a comprehensive palliative care treatment in advanced cancer patients having high (HPSG) and low symptom goals (LPSG)., Patients and Methods: Advanced cancer patients admitted to palliative care units rated symptoms intensity by the Edmonton Symptom Assessment Score (ESAS) at admission and then after one week of comprehensive palliative care treatment. For each symptom, patients were divided into two groups, according to their patient symptom goal (PSG): ≥4 (HPSG), and 0-2 (LPSG). PGI and PSGR were evaluated after one week of palliative care. The Memorial Delirium Assessment Scale (MDAS) was assessed at admission., Results: After one week of palliative care, changes in ESAS items were significantly larger in the HPSG group. HPSG patients had a better PGI and reached their target more frequently than LPSG patients for pain, weakness, and poor well-being. LPSG patients were more likely to obtain their target for appetite and insomnia. HPSG patients were more likely to have a lower Karnofsky, a lower educational level, older age, or higher MDAS values for the different ESAS items., Conclusion: Advanced cancer patients with low expectations (HPSG) were more likely to achieve their PSGR after a comprehensive palliative care treatment, reporting also a better PGI for some leading symptoms such as pain, weakness, and poor well-being. More fragile patients seem to have lower expectations and to be more likely to be satisfied., (© 2020 John Wiley & Sons Ltd.)

Background: Bone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy., Methods: Patients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12 months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value < 0.05)., Results: Of 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53-93] years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed., Conclusions: AAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R. Bordonaro discloses honoraria/consulting or advisory role/speaker’s bureau from Bayer, AstraZeneca, Sanofi, Novartis, Amgen, Roche, Pfizer, Janssen Cilag, Bristol Mayer Squibb; travel accommodations expenses from Bayer, Pfizer, Astellas, Roche; fellowship or research program from AstraZeneca, Astellas. V.E. Chiuri discloses fees for Advisory Board and speaker from Bristol Mayer Squibb, Ipsen, Janssen Cilag and Pfizer. P. Carlini discloses congressional sponsorships from Sanofi, Aventis, Bayer SPA, Astellas, Janssen Cilag. F. Panebianco and P. Beccaglia are Janssen Cilag employees. G. Procopio discloses consultant or advisory board from AstraZeneca, Bayer, Bristol Mayer Squibb, Ipsen, Janssen Cilag, Merk, MSD, Pfizer, Novartis. The other authors have nothing to disclose., (© 2020 The Authors.)

In recent years, we have witnessed a growing interest in the prevention of the loss of reproductive efficacy in young women as a result of cancer or its treatments. Indeed, recent studies have shown that loss of fertility impacts deeply on young women and sometimes may be even more stressful than the cancer diagnosis itself. In fact, the risk of treatment-associated infertility and premature menopause is a major concern for patients. Nevertheless, the approach to fertility preservation in women diagnosed with cancer is far from being standardized, and counseling strategies are poorly adopted in clinical practice. In Italy, the federal structure of public health makes it difficult to refer patients to local referral centers experienced in fertility preservation. In particular, a need exists to identify oncologists in the Lazio region specialized in fertility preservation and those facilities who are able to counsel patients regarding their sexuality. For these reasons, the Lazio section of Italian Association of Medical Oncology has led an oncofertility and oncosexuality survey to assess deficiencies in the path to start fertility preservation procedures and to help patients with cancer-related sexual problems. In total, 273 healthcare providers participated in the survey. Overall, the participants had a low interest in their patients' infertility problems, which led to a poor referral of patients to fertility preservation centers. This behavior demonstrated by healthcare providers is attributed to the necessity to rapidly start oncological treatments, the lack of knowledge of referral centers, and the little experience in tackling the subject with the patients. The interviewees also recognize communication difficulties related to lack of information on issues, absence of rehabilitations paths, and embarrassment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Until recently, conclusive data on clinical presentation, diagnosis and therapy of the opioid-induced constipation (OIC) were not available. Lately, some phase II and III prospective studies, evaluating the efficay of several old and new laxatives in cancer and non-cancer patients, make their mechanisms of action easier to understand and lead healthcare institutions to determine homogeneous guidelines for OIC, with the use of diagnostic and treatment algorithms. On May 2018, management recommendations from a panel of 7 European experts on OIC was published on United European Gastroenterology Journal. They discussed on different aspects of OIC: (a) definitions and diagnostic criteria; (b) pathophysiology; (c) clinical evaluation; (d) patient reported outcome measures; (e) initial standard laxatives; (f) specific treatments; (g) pragmatic recommendations. Later, a multi-disciplinary panel consisting of experts in neurogastroenterology, oncology and palliative medicine gave their external input. This statement will help clinicians to harmoniously treat OIC, according to clear guidelines, resulted from phase II and III prospective studies. Nevertheless, the constipation is rarely due to opioids consumption alone. More often, different factors contribute to induce constipation, including diet, immobility, other drugs, pain during evacuation, comorbidities, gastrointestinal obstacles, especially in advanced cancer patients. Therefore, management of OIC always needs to be tailored to the individual patient based on their overall clinical picture.

Purpose: to investigate clinical outcomes in patients with large brain metastases from non-small-cell lung cancer (NSCLC) who received surgical resection and postoperative stereotactic radiosurgery or SRS alone., Patients and Methods: Two hundred and twenty-two patients with 241 large brain metastases (2-4 cm in size) who received surgery and multi-fraction SRS (mfSRS) to the resection cavity or mfSRS alone were analyzed. For all lesions the delivered dose was 3 x 9 Gy over three consecutive days. Primary endpoint of the study was local control (LC). Secondary endpoints included early improvement of neurological deficits, changes in performance status, treatment-related toxicity, radiation-induced brain necrosis (RN), distant brain failure (DBF), and overall survival (OS). Kaplan-Meier analysis and cumulative incidence function were used for comparing the probability of failure., Results: At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: 13.5 months and 59% for patients receiving surgery and postoperative mfSRS to the resection cavity and 15.2 months and 68% for those treated with mfSRS alone (p = 0.2). Median DBF did not differ significantly between groups (surgery and mfSRS,12 months; mfSRS,14 months). Eighteen patients receiving surgery and mfSRS and 17 patients treated with mfSRS alone recurred locally (p = 0.2); respective 6-month and 12-month LC rates were 87% and 83% and 96% and 91% (p = 0.15). The 1-year cumulative incidence rates of RN were 15% and 7% after postoperative mfSRS and mfSRS alone (p = 0.03), respectively., Conclusions: In conclusion, mfSRS is an effective treatment for patients with large brain metastases from NSCLC resulting in equivalent LC and lower RN and risk of leptomeningeal spread compared to surgery and mf-SRS to the resection cavity. Surgery is an effective treatment option for patients with large symptomatic brain metastases who require rapid relief of neurological symptoms caused by tumor mass effect., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A consensus document on early palliative care was produced by a committed Working Group of the Italian Society of Medical Oncology and the Italian Society of Palliative Care to improve the early integration of palliative care in medical oncology and to stimulate and guide the choices of those who daily face the problems of advanced stage cancer patients. The simultaneous administration of antineoplastic treatments and early palliative care was shown to be beneficial in metastatic cancer pathway outcomes. Patients who could benefit from early palliative care are those with an advanced cancer at presentation, a compromised PS for cancer, and/or morbidities, and who are too frail to receive treatment. According to the Bruera practice models, in which the combination of cancer management with early palliative care can be offered, three groups of patients needing simultaneous care were identified and three different models of the delivery of palliative care were proposed. In patients with good prognosis and low need of simultaneous care, the solo practice model and the request for consultations were suggested, while in patients with poor prognosis disease with high need of simultaneous care and in conditions with high need of simultaneous care, regardless of cancer prognosis, the integrated care approach should be offered. Palliative care consultation services are seldom accessible in the majority of Italian hospitals; thus the application of various practice models depends on available resources, and a shared care model with the structures of palliative care operating in the area is often required.

Background: The aim of this study was to assess the patients' global impression (PGI) after symptom management, as well as the achievement of personalized symptom goals (PSG). The secondary outcome was to assess related factors., Subjects, Materials, and Methods: Advanced cancer patients admitted to palliative care units rated symptom intensity by using the Edmonton Symptom Assessment Score (ESAS) at admission and then after 1 week. For each symptom, patient-reported PGI and PSG, as well as the rate of PSG response, were evaluated., Results: Eight hundred seventy-six patients were taken into consideration for this study. A mean of 1.71-2.16 points was necessary to perceive a bit better improvement of symptom intensity. Most patients had a PSG of ≤3. A statistically significant number of patients achieved their PSG after starting palliative care. Patients with high intensity of ESAS items at admission achieved a more favorable PGI response. In the multivariate analysis, symptom intensity and PSG were the most frequent factors independently associated to a best PGI, whereas high levels of Karnofsky had a lower odd ratio., Conclusion: PSG and PGI seem to be relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response., Implications for Practice: Personalized symptom goals and global impression of change are relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Background: The clinical response after comprehensive symptom management is difficult to determine in terms of a clinically important difference. Moreover, therapies should try to reach the threshold perceived by the individual patient for the determination of a favorable response to a treatment., Measures: The Edmonton Symptom Assessment Score (ESAS) was measured at admission (T0), and seven days after starting palliative care (T7). Patient Global Impression and Goal Response after one week of palliative care and its relation with the Personalized Dyspnea Goal were measured at T7., Intervention: Patients admitted to palliative care units underwent a comprehensive symptom assessment by a specialist palliative care team. At T0, patients were asked about their Personalized Dyspnea Intensity Goal on ESAS. One week later (T7), after a comprehensive palliative care treatment, Personalized Dyspnea Intensity Goals were measured again. Patients were considered to have achieved a Patient Dyspnea Goal Response if dyspnea intensity (measured at T7) was equal or less than their expected Personalized Dyspnea Intensity Goal. At the same interval (T7), Patient Global Impression (improvement or deterioration) was measured., Outcomes: 279 patients were analyzed in this study. The mean Personalized Dyspnea Intensity Goal at T0 and T7 were 0.97 (SD 1.3), and 0.71 (SD 2.1), respectively. 263 patients (94.2%) indicated a Personalized Dyspnea Intensity Goal of ≤3 as a target at T0. Patients perceived a bit better, a better improvement, and a much better improvement with a mean decrease in dyspnea intensity of -2.1, -3.5, and -4.3 points on the dyspnea intensity scale, respectively. In 60 patients (21.5%), dyspnea intensity did not change, and in 4.7%, dyspnea intensity worsened. Patients perceived a Minimal Clinically Important Difference (little worse) with a mean increase in dyspnea intensity of 0.10, and they perceived a worse with a mean increase of 1.7 points. Higher dyspnea intensity at T0 and lower dyspnea intensity at T7 were independently related to Patient Global Impression. At T7, 93 (33.3%) patients achieved their Personalized Goal Response, based on Personalized Dyspnea Intensity. Patient Dyspnea Goal Response was associated with Memorial Delirium Assessment Scale score and Personalized Dyspnea Intensity Goal at T0, and inversely associated with dyspnea intensity at T0 and T7, and lower Karnofsky level. For Patient Dyspnea Goal Response, no significant differences among categories of dyspnea intensity were found (P>0.05)., Conclusion: Patient Dyspnea Goal Response and Patient Global Impression seem to be relevant for evaluating the effects of a comprehensive management of symptoms, including dyspnea, assisting decision making process. Some factors may be implicated in determining the individual target and clinical response. A personalized symptom goal may translate in terms of therapeutic intervention, according to the achievement of the patients' expectations. High values of dyspnea intensity, a lower Karnofsky level, as well as high level of Dyspnea Intensity Goal (that is less patients' expectations) favor the achievement of the target., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Cancer-related bone pain is a frequent and important key problem for metastatic patients that may reduce quality of life, with related limitations in daily activities and morbidity. Often traditional approach to pain may fail given the complex pathophysiology of this phenomenon., Methods: The aim of this review is to describe promising therapies for cancer-related bone pain, from the pathophysiology to the clinical trials currently ongoing. Moreover, any new evidence for better approach to cancer-related bone pain with the traditional drugs is also considered., Conclusions: In clinical practice opioids remain the most important pharmacologic treatment for severe pain related to bone cancer. Regard developing drugs, anti-NGF and anti-TrkA are the most investigated new drug in this setting, but a future role in clinical practice is still uncertain., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To investigate local control and radiation-induced brain necrosis in patients with melanoma brain metastases who received complete resection plus fractionated stereotactic radiosurgery (fSRS, 3 × 9 Gy) or fSRS alone. Factors associated with the clinical outcomes and the development of brain necrosis have been assessed. One hundred and twenty consecutive patients with 137 melanoma brain metastases who received surgery plus fSRS (S + fSRS) or fSRS alone were analyzed. All lesions evaluated in the study were treated with a dose of 27 Gy given in 3 fractions over three consecutive days. Cumulative incidence analysis was used to compare local failure (LF), distant brain failure (DBF), and radiation-induced brain necrosis (RN) between groups from the time of SRS. At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: S + fSRS, 14 months and 85%; fSRS, 12 months and 85% (p = 0.2). Median DBF did not differ significantly by group, being 14 months for both groups. Nine patients who received S + fSRS and 20 patients treated with fSRS recurred locally (p = 0.03). Six-month and 1-year LF rates were 5 and 12% in S + fSRS group and 17 and 28% in fSRS group (p = 0.02). RN occurred in 21 patients (S + fSRS, n = 14; fSRS, n = 7; p = 0.1). The cumulative 1-year incidence of RN was 13% after S + fSRS and 8% after fSRS (p = 0.15). In conclusion, postoperative SRS (3 × 9 Gy) to the resection cavity is an effective treatment modality for melanoma brain metastases associated with better local control as compared with fSRS alone.

One of the priorities of personalized medicine regards the role of early integration of palliative care with cancer-directed treatments, called simultaneous care. This article, written by the Italian Association of Medical Oncology (AIOM) Simultaneous and Continuous Care Task Force, represents the position of Italian medical oncologists about simultaneous care, and is the result of a 2-step project: a Web-based survey among medical oncologists and a consensus conference. We present the opinion of more than 600 oncologists who helped formulate these recommendations. This document covers 4 main aspects of simultaneous care: 1) ethical, cultural, and relational aspects of cancer and implications for patient communication; 2) training of medical oncologists in palliative medicine; 3) research on the integration between cancer treatments and palliative care; and 4) organizational and management models for the realization of simultaneous care. The resulting recommendations highlight the role of skills and competence in palliative care along with implementation of adequate organizational models to accomplish simultaneous care, which is considered a high priority of AIOM in order to grant the best quality of life for cancer patients and their families.

Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data vs. predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment. Materials and methods : We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS) and response rate (RR). OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models. Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI] = 16.6-39.7%) and median OS and PFS were 20 (95% CI = 20-21) and 12 (95% CI = 12, 16) weeks, respectively. Visceral metastasis (VM) and hemoglobin (Hb) ≤ 10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI) of 24 (20-40) weeks and 1-year (95% CI) OS of 13.7% (4.4-42.7%), while the 37 patients with 1 or 2 risk factors had median OS (95% CI) of 20 (16-20) weeks and 1-year (95% CI) OS of 6.7% (1.8-24.9%). Cetuximab-including regimens were associated with a trend for improved RR compared to other agents (Odds ratio = 5.05, 95% CI = 0.84-30.37, p = 0.077). Taxanes vs. non-taxane, and combination vs. single agent therapy was not associated with improved outcomes. The study is limited by its modest sample size. Conclusion: This is the first prognostic classification proposed for patients receiving salvage systemic therapy for advanced PSCC. The presence of VM and Hb ≤ 10 gm/dl was associated with poor OS and PFS. Cetuximab appeared to be associated with better RR. This prognostic model may assist in salvage therapy drug development for this orphan disease by improving interpretation of outcomes seen in nonrandomized data.

Background: Trials of salvage therapy for advanced urothelial carcinoma have required prior platinum-based therapy. This practice requires scrutiny because non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients., Patients and Methods: Data of patients receiving salvage systemic chemotherapy were collected. Data on prior first-line platinum exposure were required in addition to treatment-free interval, hemoglobin, Eastern Cooperative Oncology Group performance status, albumin, and liver metastasis status. Cox proportional hazard regression was used to evaluate their association with overall survival (OS) after accounting for salvage single-agent or combination chemotherapy., Results: Data were obtained from 455 patients previously exposed to platinum-based therapy and 37 not exposed to platinum. In the group exposed to prior platinum therapy, salvage therapy consisted of a single-agent taxane (n = 184) or a taxane-containing combination chemotherapy (n = 271). In the group not exposed to prior platinum therapy, salvage therapy consisted of taxane or vinflunine (n = 20), 5-fluorouracil (n = 1), taxane-containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2), and cisplatin-based combinations (n = 2). The median OS for the prior platinum therapy group was 7.8 months (95% confidence interval, 7.0, 8.1), and for the group that had not received prior platinum therapy was 9.0 months (95% confidence interval, 6.0, 11.0; P = .50). In the multivariable analysis, prior platinum therapy versus no prior platinum exposure did not confer an independent impact on OS (hazard ratio, 1.10; 95% confidence interval, 0.75, 1.64; P = .62)., Conclusion: Prior platinum- versus non-platinum-based chemotherapy did not have a prognostic impact on OS after accounting for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Lack of prior platinum therapy should not disqualify patients from inclusion onto trials of salvage therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Early integration of palliative care in oncology practice ("simultaneous care", SC) has been shown to provide better care resulting in improved quality-of-life and also survival. We evaluated the opinions of Italian Association of Medical Oncology (AIOM) members., Patients and Methods: A 37-item questionnaire was delivered to 1119 AIOM members. Main areas covered were: social, ethical, relational aspects of disease and communication, training, research, organizational and management models in SC. Three open questions explored the definition of Quality of Life, Medical Oncologist and Palliative Care., Results: Four hundred and forty-nine (40.1%) medical oncologists returned the questionnaires. Forty-nine percent stated they address non-curability when giving a diagnosis of metastatic tumor, and 43% give the information only to patients who clearly ask for it. Fifty-five percent say the main formative activity in palliative medicine came from attending meetings and 90% agree that specific palliative care training should be part of the core curriculum in oncology. Twenty-two percent stated they consulted guidelines for symptom management, 45% relied upon personal experience and 26% make a referral to a palliative care specialist. Seventy-four percent were in favor of more research in palliative medicine. An integration between Units of Oncology and Palliative Care Services early in the course of advanced disease was advocated by 86%. Diverse and multifaceted definitions were given for the concepts of Quality of Life, Palliative Care and Medical Oncologist., Conclusion: SC is felt as an important task, as well as training of medical oncologists in symptom management and research in this field., Competing Interests: The authors have declared no conflicts of interest.

Purpose: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed., Methods and Materials: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, a propensity score analysis was used., Results: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment., Conclusions: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.