How to become a Multinational Association of Supportive Care in Cancer-designated center of excellence in supportive care in cancer.

PURPOSE OF REVIEW: Aim of this review is to encourage and involve more doctors to take care of supportive care in cancer patients and to become centers of excellence. RECENT FINDINGS: In 2019, MASCC initiated a certification program to recognize oncology centers that demonstrate best practices in supportive cancer care but literature on how to become MASCC-designated center of Excellence in Supportive Care in Cancer is scarce and will be bulleted. SUMMARY: Becoming centers of excellence means not only the recognition of the clinical and managerial requirements to provide good supportive care but also the creation of a network of centers to participate in multicenter scientific projects and thus improve knowledge in the field of supportive care in cancer patients.

Cytokinetic-driven myeloprotection after cytotoxic chemotherapy: from an old idea to a new clinical approach.

Chemotherapy is the backbone of the treatment of several solid tumours and lymphomas. Myelotoxicity is often a dose-limiting toxicity and myeloprotection has always been investigated. In fact, over the years, several approaches have been studied in order to reduce the incidence of haematological toxicities and allow patients to receive effective, full-dose, chemotherapy. After the use of stimulating factors, such as granulocyte colony-stimulating factors and erythropoiesis-stimulating agents, in the very last years, a new approach has emerged. Trilaciclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, has been studied and it has been demonstrated in several clinical trials to reduce the incidence of myelotoxicity in small-cell lung cancer patients treated with chemotherapy or chemo-immunotherapy. Its potential role has not been fully studied yet, but it represents a highly effective tool to reduce myelotoxicity, widen the applicability of full-dose chemotherapy, even in frailer patients, and finally to increase the efficacy of chemotherapy in those tumours where relative dose intensity is a standard to achieve to get the best clinical results.

Peripherally or centrally inserted central catheters: what is the best vascular access device for cancer patients?

Choosing the appropriate vascular access device is a pivotal step to guarantee vessel health and preservation in cancer patients. The first turning point is the determination of the need for central venous catheters (CVCs) followed by the selection of the CVC that will complete the prescribed treatment while minimizing complications and satisfying patients' needs and expectations. Peripherally inserted central catheters (PICCs) have steadily grown over the years as an alternative to centrally inserted central catheters and totally implantable catheters based on several advantages including avoidance of placement-associated mechanical complications, easier transitions from hospital to intermediate care settings and home, but also increase in healthcare expenditure, supportive reimbursement policies, and ability to train existing staff. Notwithstanding PICCs have been perceived for a long time as associated with fewer complications, reduced costs, and higher patients' satisfaction compared to other CVCs, recent evidence has raised concerns about their safety profile without any benefits for longer-term costs neither for patients' satisfaction. This commentary offers a comprehensive overview on PICC-related (1) complications, (2) costs, and (3) patients' satisfaction to help healthcare professionals in the choice of the vascular device during their clinical practice. Based on the most recent literature, we finally suggested that the choice of the CVC should depend on the clinical situation with totally implantable catheters being the preferred device for patients who need intermittent long-term and high-dose chemotherapy, while PICCs may be a better choice for patients who need short-term chemotherapy or continuous short-term supportive therapy.

Immunotherapy in Underrepresented Populations of Patients with Cancer: Do We Have Enough Evidence at Present? A Focus on Patients with Major Viral Infections and Autoimmune Disorders.

The safety and activity of immune checkpoint inhibitors have been characterized in interventional and observational studies. However, only small studies have specifically investigated these agents in patients who are excluded or underrepresented in clinical trials, frequently referred to as "special populations" or "underrepresented populations." These include older adults, those with dysregulated immune activation, patients with a compromised immune function, and those carrying major viral infections, lymphoproliferative diseases, and major organ dysfunctions. Therefore, there remains substantial uncertainty regarding the use of immune checkpoint inhibitors in these specific settings. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project, with the contribution of oncologists and other specialists, to retrieve the existing evidence on the use of immunotherapy in patients with solid and hematological cancers with the final aim to provide an expert guidance. The results of this effort are presented in this article, which is focused on patients with major viral infections or those with immune dysregulation/autoimmune diseases, and could be useful to guide decisions in clinical practice and to design prospective clinical trials focusing on the use of immunotherapy in these populations. IMPLICATIONS FOR PRACTICE: Substantial uncertainty remains regarding the use of immune checkpoint inhibitors in "underrepresented" patients, such as older adults, those with dysregulated immune activation, and patients with a compromised immune function, major viral infections, lymphoproliferative diseases or major organ dysfunctions. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project to retrieve the existing evidence on the use of immunotherapy in underrepresented patients with cancer in order provide an expert guidance. The results of this effort, with a focus on patients with major viral infections or those with immune dysregulation/autoimmune diseases, are presented in this article and could be useful to guide decisions both in clinical practice and to design clinical trials.

Recent advances in the management of chemotherapy-induced neutropenia: biosimilar granulocyte colony-stimulating factor use in Italy.

During the National Congress of the Italian Association of Medical Oncology, which was held in Rome, Italy, October 2019, experts met to discuss advantages of febrile neutropenia prevention based on biosimilar G-CSF. This issue is of paramount importance in oncology as recent biological products may be of great benefit, provided that costs are sustainable.

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy.

Aim: Reporting toxicities of targeted therapies (TTs) and immunotherapy in oncology requires special attention. Materials & methods: We identified TTs and immunotherapies approved by the US FDA for solid malignancies in the adult population. Publications were reviewed according to a 24-point score based on the Consolidated Standards of Reporting Trials guidance. Results: We identified 81 trials (>45,000 patients). The experimental drug was studied as single agent in 51% of the cases; setting of disease was mainly (95%) advanced/metastatic. Lowest scores in adverse event (AE) description regarded: reporting recurrent/late toxicities and duration of the AEs (>90%), time of occurrence and indication of all-grade AEs (>75%). Conclusion: Suboptimal reporting of AEs in trials leading to approval of TTs and immunotherapy was shown. Improving AE descriptions should be a priority in ongoing trials.

Prevalence, characteristics, and treatment of fatigue in oncological cancer patients in Italy: a cross-sectional study of the Italian Network for Supportive Care in Cancer (NICSO).

BACKGROUND: Fatigue is one of the most distressing symptoms of cancer patients. Its characteristics and impact on quality of life have not been fully explored and treatment of cancer-related fatigue in Italian oncological centers has not been codified. METHODS: A cross-sectional study was carried out on all patients attending for any reason the 24 participating centers in two non-consecutive days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue. RESULTS: From October 2014 to May 2015, 1394 cancer patients agreed to participate in the study. Fatigue was referred by 866 (62.1%) of patients; its duration was > 4 months in 441 patients (50.9%). In the investigators' opinion, the most important (probable or almost sure) determinants of fatigue were reduced physical activity (271 patients), anxiety (149), pain (131), insomnia (125), anemia (123), and depression (123). Fatigue of moderate/severe intensity was reported by 43%/29.2% of patients, while usual fatigue in the last 24 h by 45%/33.1%, and the worst fatigue in the last 24 h by 33%/54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately/severely with general activity in 30.8%/38.6% of patients, with mood in 26.1%/32.8%, with the ability to work in 27.9%/35.6%, with normal work in 26.7%/38.9%, with relationships with others in 21%/23.4% and with the ability to amuse themselves in 22.2%/33.1%. Only 117/866 patients (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 patients (86.3%) while 188 patients (21.7%) received a non-pharmacological treatment such as physical exercise (120 patients, 63.8%) and various alimentary supplements (52 patients, 27.6%). CONCLUSIONS: Cancer-related fatigue is frequently reported by oncological patients; its intensity and impact on quality of life is relevant.

Vismodegibfor the treatment of radiation-induced basal cell carcinoma - a case report and brief literature study.

Vismodegib is playing an increasing role in the treatment of locally advanced or metastatic basal cell carcinoma (BCC) that is not a candidate for surgery or radiotherapy, and also in radiation-induced BCC. A 22-year-old man with a history of Hodgkin lymphoma, nodular sclerosis stage IIA, from October 1994 to February 1995 treated with 25 mg/m2 doxorubicin, 10 IU/m2 bleomycin, 6 mg/m2 vinblastine, and 375 mg/m2 dacarbazine for four cycles, followed byconformal beam radiotherapy (EBRT) on laterocervical, supraclavear, and mediastinal nodes up to a total dose of 30 Gy and following EBRT boost on mediastinal nodes up to a dose of 10 Gy. Subsequently, the patient underwent conformal EBRT on lomboaortic nodes up to total dose of 30 Gy at the University Hospital of Pisa until May 1995. There was no evidence of disease, until March 2012 when the patient developed severalBCCs, occurring in the field of prior radiation, treated with local excisions. No mutations of Hedgehog (Hh) pathway or other genes were found and nevoid basal cell carcinoma syndrome was not diagnosed. In February 2018, the patient began therapy with vismodegib at standard dose of 150 mgorally daily and was treated for 10 months, with low adverse events and with pathological complete response of disease until July 2019. This experience shows that there are, however very few, BCCs not associated with genetic disorders. Vismodegib seems to be an effective and safe therapeutic approach also for radiation-related BCCs, associated with relatively low toxicity.

Fatigue, a major still underestimated issue.

PURPOSE OF REVIEW: Cancer-related fatigue (CRF) is a frequent and distressing symptom present at any stage of the disease. However, it is still underreported, rarely properly assessed and undertreated. RECENT FINDINGS: There are international guidelines available, but also several barriers to their implementation into clinical practice. SUMMARY: According to guidelines, all patients should be clinically screened for CRF on regular basis, at the initial cancer visit and at intervals during every clinic visit, also at posttreatment follow-up visits. Generally, any treatable contributing factors should be identified and possibly treated. After the concomitant factors have been improved or removed, pharmacological and or nonpharmacological treatments of CRF can be considered.Further research is needed to better understand the causes, the better treatments, the easier assessment tool for CRF for clinical practice and to identify barriers and facilitators to implementing CRF guidelines.

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors.

PURPOSE: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. METHODS: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples. RESULTS: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. CONCLUSION: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

Use of procalcitonin in clinical oncology: a literature review.

The use of procalcitonin (PCT) as an early marker of infectious episodes in cancer patients is still controversial. We performed a MEDLINE search of peer-reviewed articles published between January 1990 and December 2015, and finally we analysed 15 articles. PCT seems to have a good diagnostic value of infectious episodes in cancer patients and its accuracy seems greater if we consider major events, such as bloodstream infections and sepsis. Serial evaluations of this protein seem to be more accurate in the diagnostic phase and useful to predict outcome and response to antibacterial treatment. On the other hand, some issues have yet to be solved, such as the use of a validated method of determination, the definition of a standard cut-off, and the heterogeneity among different settings of patients (e.g. early versus advanced-stage cancer, or haematological versus solid tumours). However, it is credible to think that PCT use in everyday clinical practice, preferably in combination with other clinical or laboratory tests, might be of help in finding and detecting early infectious complications in cancer patients.

Docetaxel plus oral metronomic cyclophosphamide: a phase II study with pharmacodynamic and pharmacogenetic analyses in castration-resistant prostate cancer patients.

BACKGROUND: Docetaxel plus prednisone is currently the standard first-line treatment in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess the clinical activity and pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in combination with metronomic cyclophosphamide in mCRPC patients. METHODS: Forty-one chemotherapy-naive patients received docetaxel (60 mg/m(2) intravenously every 3 weeks up to 12 cycles) and, from day 2, prednisone 10 mg/day, celecoxib 400 mg/day, and metronomic cyclophosphamide 50 mg/day, continuously. Plasma VEGF and bFGF were detected by ELISA. Real-time PCR-SNP analysis of VEGF gene was performed using an ABI PRISM 7900HT SDS and TaqMan SNP genotyping. RESULTS: Eighty-seven percent of patients were free of progression at 6 months. A decrease in prostate-specific antigen ≥50% was observed in 82% of 39 evaluable patients, with a median time to progression of 12.3 months. Grade 3 adverse events were neutropenia (5%), thrombocytopenia, diarrhea, and stomatitis (2.5%). Median PFS and OS were 14.9 months (95% CI, 9.2-15.3 months) and 33.3 months (95% CI, 23-35.6 months), respectively. Of 11 patients (28%) with evaluable disease, 5 (44%) achieved a complete response, 2 (11%) a partial response, and 2 (11%) stable disease, whereas 2 showed disease progression. The -1154A/G VEGF polymorphism, plasma VEGF, and bFGF after the first cycle of chemotherapy may represent useful pharmacodynamic markers to predict better outcomes. CONCLUSIONS: The combination of docetaxel and oral metronomic chemotherapy is effective and well tolerated in mCRPC patients and may deserve further evaluation.

Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases.

Patients with melanoma brain metastases have a poor prognosis and historically have been excluded from clinical trials. The Expanded Access Program (EAP) provided an opportunity to evaluate the feasibility of ipilimumab (3 mg/kg every 3 weeks for four doses) in patients with stage 3 (unresectable) or 4 melanoma and asymptomatic brain metastases, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Tumor assessments were conducted at baseline and week 12 using immune-related response criteria and patients were monitored for adverse events (AEs). Of 855 patients participating in the EAP in Italy, 146 had asymptomatic brain metastases. With a median follow-up of 4 months, the global disease control rate was 27%, including 4 patients with a complete response and 13 with a partial response. Median progression-free survival and overall survival were 2.8 and 4.3 months, respectively and approximately one-fifth of patients were alive 1 year after starting ipilimumab. In total, 29% of patients reported a treatment-related AE of any grade, which were grade 3/4 in 6% of patients. AEs were generally reversible with treatment as per protocol-specific guidelines. Ipilimumab shows durable benefits in some patients with advanced melanoma metastatic to the brain, with safety results consistent with those previously reported in clinical trials.

Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions.

Immune checkpoint inhibitor-based therapies represent the current standard of care in the first-line treatment of advanced renal cell carcinoma. Despite a clear benefit in survival outcomes, a considerable proportion of patients experience disease progression; prospective data about second-line therapy after first-line treatment with immune checkpoint inhibitors are limited to small phase II studies. As with other solid tumors (such as melanoma and non-small cell lung cancer), preliminary data about the clinical efficacy of rechallenge of immunotherapy (alone or in combination with other drugs) in renal cell carcinoma are beginning to emerge. Nevertheless, the role of rechallenge in immunotherapy in this setting of disease remains unclear and cannot be considered a standard of care; currently some randomized trials are exploring this approach in patients with metastatic renal cell carcinoma. The aim of our review is to summarize main evidence available in the literature concerning immunotherapy rechallenge in renal carcinoma, especially focusing on biological rationale of resistance to immune checkpoint inhibitors, on the published data of clinical efficacy and on future perspectives.

Steroid treatment in the management of destructive thyrotoxicosis induced by PD1 blockade.

Objective: Destructive thyroiditis is the most common endocrine immune-related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless, in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. The aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods: We conducted a retrospective study, comparing the course of thyrotoxicosis of four patients treated with oral prednisone at the dosage of 25 mg/day (tapered to discontinuation in 3 weeks) and an enlarged thyroid volume to that of eight patients with similar thyroid volume who were left untreated. Results: The levels of thyroid hormones were lower in subjects treated compared to those untreated at time of 7, 14, 21, 28, 35, 42, 60 and 90 days (P < 0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P < 0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the two groups (4/4 in the steroid group vs 7/8 in the untreated group, P = 0.74) and no difference was found in tumor progression (P = 0.89). Conclusions: Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones.

Safety and Tolerability of COVID-19 Vaccines in Patients with Cancer: A Single Center Retrospective Analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused a worldwide challenging and threatening pandemic. Multinational, placebo-controlled, observer-blinded trials were conducted since the beginning of pandemic because safe and effective vaccines were needed urgently. In most trials of COVID-19 vaccines patients affected by malignancies or on treatment with immunosuppressive drugs were excluded. PATIENTS AND METHODS: A retrospective monocentric study was conducted at Medical Oncological Unit of Santa Chiara Hospital (Pisa, Italy) in this subset of population to investigate safety and tolerability of COVID-19 vaccines; 377 patients with solid tumor on treatment were enrolled. Vaccine-related adverse events were recorded using a face-to-face questionnaire including a toxicity grading scale. Most of the patients (94%) received mRNA vaccine as indicated by Italian health ministry guidelines. Mean age was 66 years (range 27-87), 62% of the patients were older than 65 years and 68% had at least one additional comorbidity. The majority (86%) of patients were in a metastatic setting and 29% received immunotherapy-based treatment. For statistical analysis, multivariate binary logistic regression models were performed and linear regression models were applied. RESULTS: Adverse events were mild and transient and ended in a few days without any sequelae. No severe or uncommon adverse events were recorded. In multivariate analysis, we found that the female sex was associated with a greater risk of more severe and longer lasting adverse events, and a higher risk of adverse events was found for patients treated with immunotherapy. CONCLUSIONS: Our results demonstrate that COVID-19 vaccines were safe and well-tolerated in this population of patients being treated for solid tumors.

Prognostic role of hematologic parameters of metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: Hemochrome parameters at the diagnosis of metastatic renal cell carcinoma (mRCC) and the development of macrocytosis during sunitinib therapy are considered prognostic. OBJECTIVE: To evaluate the prognostic role of hematologic parameters and macrocytosis in mRCC treated with sunitinib. METHODS: We analyzed clinical data of 100 patients with mRCC treated with sunitinib as first-line therapy in a retrospective multicenter study. We calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) at baseline and erythrocyte mean corpuscular volume (MCV) during therapy. We considered the following cutoffs: NLR >3, PLR >150, LMR <3, and MCV >100 fl. Clinical data histology, prior nephrectomy, Fuhrman grading, metastatic sites, Memorial Sloan-Kettering Cancer Center score, and Heng score were collected. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariate and multivariate analysis using Cox regression model with time-dependent (macrocytosis) covariate were applied. RESULTS: At the univariate analysis, low LMR was associated with shorter PFS and OS (p = 0.02 and p = 0.06, respectively). High PLR was associated with worse PFS (p = 0.005); median OS was 23 vs 28 months (p = 0.13). At the multivariate analysis, poor risk (Heng score), low LMR, and high PLR were associated with shorter PFS (hazard ratio 7.1, 1.5, and 2, respectively); poor PS and poor risk (Heng score) were related to worst OS. Macrocytosis was observed in 26 patients and was not prognostic of survival. CONCLUSIONS: In our cohort of patients with mRCC treated with sunitinib, low LMR (>3) and high PLR (>150) were associated with shorter PFS. Macrocytosis was not prognostic.

Effectiveness of a phone-based nurse monitoring assessment and intervention for chemotherapy-related toxicity: A randomized multicenter trial.

Purpose: Anticancer treatment-related toxicities can impact morbidity and mortality, hamper the administration of treatment, worsen the quality of life and increase the burden on the healthcare system. Therefore, their prompt identification is crucial. NICSO (Italian Network for Supportive Care in Cancer) conducted a nationwide randomized trial to evaluate the role of a planned, weekly phone-based nurse monitoring intervention to prevent and treat chemotherapy, targeted therapy- and immunotherapy-related toxicities. Here, we report the results from the chemotherapy arm. Methods: This was a nationwide, randomized, open-label trial conducted among 29 Italian centers (NCT04726020) involving adult patients with breast, colon, or lung cancer and a life expectancy ≥6 months receiving adjuvant chemotherapy. Patients received either a weekly nurse monitoring phone call and an educational leaflet reporting practical advice about prevention and treatment of toxicities (experimental group) or the educational leaflet only (control group). Results: The addition of a nurse monitoring intervention may help reduce time spent with severe toxicities (grade ≥3), particularly those less frequently reported in clinical practice, such as fatigue. When considering grade 1-2 AEs, times with mild/moderate diarrhea, mucositis, fatigue and pain were shorter in the experimental arm. Time spent without AEs was significantly longer in the experimental arms for all the toxicities. The requirement for special medical attention was comparable between groups. Conclusion: This study suggests the need for implementing a better system of toxicity assessment and management for patients treated with adjuvant chemotherapy to promote effective preventive and/or therapeutic intervention against these events.