Analysis of the adequacy of control arms in oncology randomised clinical trials published between 2017 and 2021: a meta-research study.

INTRODUCTION: Randomised controlled trials (RCTs) are usually considered the highest level of evidence for clinical practice. Patients assigned to control arm in RCTs should always receive the best available treatments to protect participants while also allowing for proper interpretation and applicability of study results. Here we analysed RCTs published in oncology between 2017 and 2021 to describe the frequency of suboptimal control arms. METHODS: We identified phase III studies testing active treatments in patients with solid tumours among 11 major oncology journals. Each control arm was analysed, and the standard of care was determined according to international guidelines and scientific evidence at accrual beginning and until accrual completion. We identified studies with suboptimal control arm from the beginning (type 1) and studies with an initially optimal control arm which became outdated during the accrual period (type 2). RESULTS: This analysis included 387 studies. Forty-three (11.1%) control arms were judged as suboptimal: 24 (6.2%) type 1 and 19 (4.9%) type 2. These rates were higher in industry-sponsored compared to academic trials: 9.3% versus 1.9% for type 1 (p = 0.003); 7.9% versus 0.6% for type 2 (p = 0.001). Rates of suboptimal control arms were higher in studies with positive results: 8.1% versus 4.0% for type 1 (p = 0.09); 7.6% versus 1.7% for type 2 (p = 0.007). CONCLUSIONS: Many trials have suboptimal control arms, even in journals with high-impact factors, leading to suboptimal treatment of control patients and biased evaluation of trial results.

Therapeutic sequencing in advanced renal cell carcinoma: How to choose considering clinical and biological factors.

In the last fifteen years a better understanding of the biological processes promoting tumour growth and progression led to an impressive revolution in metastatic renal cell carcinoma (mRCC) treatment landscape. Angiogenesis plays a critical role in the pathogenesis of RCC. These biological evidences led to targeted therapies interfering with vascular endothelial growth factor and mammalian target of rapamycin pathway. Another big step in the RCC therapeutic landscape was recently made because of the understanding of the interplay between angiogenesis and immune cells. Dual immune checkpoint inhibitors (ICIs) and ICIs plus tyrosine kinase inhibitors (TKI) combinations have been approved considering overall survival benefit compared to targeted therapies as first line treatment. We summarize the activity and the biological rationale of ICIs combinations as mRCC first line therapy. Additionally, we review the clinical and biological criteria useful to guide clinicians in the choice of treatment sequencing focusing on ICIs combinations resistance mechanisms.

Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis.

BACKGROUND: Radium 223 (Ra-223) was approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) patients with bone-only disease, following demonstration of significant improvement in overall survival (OS). To date, there are no validated prognostic factors useful in predicting outcome of mCRPC patients treated with Ra-223. Our retrospective study aims to evaluate the prognostic role of treatment discontinuation due to adverse events in mCRPC patients treated with Ra-223, and to identify which factors correlate with the toxicity onset. METHODS: We performed a retrospective analysis of all consecutive mCRPC patients treated with Ra-223 from September 2013 to December 2019 at our institute. Patients were divided in 2 groups according to the reason of Ra-223 therapy discontinuation: toxicity versus other causes. Outcome measures were progression-free survival (PFS) and OS. RESULTS: In the overall population (75 patients) median PFS and OS were 5.46 months and 11.15 months respectively. Patients who discontinued treatment due to toxicity had a lower median PFS (3.49 vs 5.89 months, HR: 1.88, 95% CI: 1.14-3.12, p = 0.014) and OS (8.59 vs 14.7 months HR: 3.33, 95% CI: 1.85-6.01, p < 0.001) than patients who discontinued therapy due to other causes. The risk of Ra-223 discontinuation due to toxicity correlates with the number of previous treatments (p = 0.002), previous chemotherapy treatment (p = 0.039), baseline LDH (p = 0.012), Hb (p = 0.021) and platelet-to-lymphocyte ratio (p = 0.024). CONCLUSIONS: Discontinuation due to toxicity is associated with worse outcomes in mCRPC patients treated with Ra-223. To reduce the risk of developing toxicities that may compromise treatment efficacy, Ra-223 should be used early in mCRPC patients.

Metastatic Urothelial Carcinoma: Have We Take the Road to the Personalized Medicine?

Urothelial cancer is a lethal malignancy characterized by a wide diffusion in Western countries due to a larger exposure to known risk factors, such as aromatic amines, tobacco smoke and benzene [...].

New emerging targets in advanced urothelial carcinoma: Is it the primetime for personalized medicine?

In recent years the introduction of immunotherapy has importantly changed the treatment landscape of advanced urothelial carcinoma. Several immune checkpoint inhibitors are now the standard of care as maintenance treatment after disease control with platinum-based first-line chemotherapy (avelumab), in subsequent lines (pembrolizumab) or as upfront therapy in platinum-ineligible patients (atezolizumab or pembrolizumab). Moreover, personalized therapy based on tumor molecular features has been developed. Namely, the increasing knowledge of the pathogenesis and molecular pathways underlying cancer development and progression is leading the introduction of target therapies such as the recently approved fibroblastic growth factor receptor (FGFR) inhibitor erdafitinib or the anti-nectin 4 antibody drug-conjugated enfortumab vedotin. Consequently, clinicians face new challenges, such as the choice of the best therapeutic sequence for each patient. The aim of this review is focusing on the emerging treatment options in metastatic urothelial carcinoma and discussing clinical features for choosing therapeutic sequencing.

New Perspectives in the Medical Treatment of Non-Muscle-Invasive Bladder Cancer: Immune Checkpoint Inhibitors and Beyond.

Non-muscle-invasive bladder cancer (NMIBC) is characterized by a high rate of cure, but also by a non-negligible probability of recurrence and risk progression to muscle-invasive disease. NMIBC management requires a proper local resection and staging, followed by a risk-based treatment with intravesical agents. For many years, the current gold standard treatment for patients with intermediate or high-risk disease is transurethral resection of the bladder (TURB) followed by intravesical bacillus Calmette-Guérin (BCG) instillations. Unfortunately, in about half of high-risk patients, intravesical BCG treatment fails and NMIBC persists or recurs early. While radical cystectomy remains the gold standard for these patients, new therapeutic targets are being individuated and studied. Radical cystectomy in fact can provide an excellent long-term disease control, but can deeply interfere with quality of life. In particular, the enhanced immune checkpoints expression shown in BCG-unresponsive patients and the activity of immune checkpoints inhibitors (ICIs) in advanced bladder cancer provided the rationale for testing ICIs in NMIBC. Recently, pembrolizumab has shown promising activity in BCG-unresponsive NMIBC patients, obtaining FDA approval. Meanwhile multiple novel drugs with alternative mechanisms of action have proven to be safe and effective in NMIBC treatment and others are under investigation. The aim of this review is to analyse and describe the clinical activity of new emerging drugs in BCG-unresponsive NMIBC focusing on immunotherapy results.

A systematic review and meta-analysis of trials assessing PD-1/PD-L1 immune checkpoint inhibitors activity in pre-treated advanced stage malignant mesothelioma.

INTRODUCTION: Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM. METHODS: A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) data were extracted. The predictive role of PD-L1 was assessed. RESULTS: We selected 13 studies including 888 patients. ORR and DCR were 18.1% (95% confidence interval [CI] 13.9-22.8%) and 55.4% (95% CI: 48.1-62.5%), respectively. Median PFS and OS ranged from 2.1 to 5.9 and from 6.7 to 20.9 months, respectively. ORR according to PD-L1 was 27.0% (95% CI: 18.7-36.2%). CONCLUSIONS: Anti-PD-(L)1 ICIs might be considered a treatment option for chemotherapy-resistant asMM, even if reliable predictive factors are still lacking.

Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation.

BACKGROUND: The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood. METHODS: The Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported. The primary end points were median progression-free survival, overall survival, objective response rate, risk of progression of disease and risk of death. The correlation of clinic pathological features with early severe irAEs represented the secondary end point. RESULTS: Median PFS was 9.3 and 8.4 months, median OS was 12.0 months and 14.2 months at a median follow-up of 18.1 and 22.6 months in the LTD cohort and in the control cohort, respectively. The ORR was 40% (95% CI 17.2-78.8) in the LTD cohort and 32.7% (95% CI 27.8-38.2) in the control cohort. The risk of disease progression was higher in the LTD cohort (HR 2.52 [95% 1.10-5.78], P = .0288). CONCLUSIONS: We found no survival benefit in LTD cohort compared to the control cohort. However, early and severe irAEs might underly an immune anti-tumor activation. We identified a significant association with first-line immune checkpoints inhibitors treatment and good PS. Further studies on risk prediction and management of serious and early irAEs in NSCLC patients are needed.

Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review.

The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was >2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.

Renal cell carcinoma (RCC): fatter is better? A review on the role of obesity in RCC.

Obesity represents a well-known risk factor for renal cell carcinoma development. Several studies evaluated the relationship between obesity and outcome in patients with non-metastatic and metastatic renal cell carcinoma using different parameters such as BMI, visceral fat area and s.c. fat area. These studies suggest that obesity is associated with a better prognosis in renal cell carcinoma patients. This phenomenon is called obesity paradox and it was found in other diseases in which obesity represents an established risk factor such as heart failure, diabetes, atrial fibrillation, hypertension and coronary heart disease. The purpose of this review is to analyze the mechanisms by which obesity increases the risk of renal cell carcinoma development, to describe the evidence available to date about the link obesity-outcome and to evaluate the mechanisms to explain this apparently paradoxical relationship.

Adoption of multiple primary endpoints in phase III trials of systemic treatments in patients with advanced solid tumours. A systematic review.

BACKGROUND AND AIM: Trial designs using multiple primary endpoints (MPEs) are increasing in phase III cancer trials. Our objectives were to describe the incidence of MPEs in recently published phase III trials testing systemic treatments in patients with advanced cancer; the main characteristics of trials adopting MPEs; the presence of mature results for all endpoints in the primary publication; consistency between results of each endpoint and authors' conclusions. METHODS: Articles of randomised phase III trials conducted in patients with advanced cancer, published between 2017 and 2020, were retrieved from PubMed. The main outcome was the proportion of trials with MPEs. In principle, according to regulatory agencies, we considered two distinct cases: (i) MPEs correspond to 'multiple chances' for the success of experimental treatment, needing adjustment for multiplicity, and (ii) a positive result depends on the success in all MPEs ('co-primary' endpoints). RESULTS: Out of 235 eligible trials, 27 trials (12%) adopted MPE, mostly overall survival (OS) and progression-free survival (PFS). The proportion of trials with MPEs increased over time, from 6% in 2017 to 20% in 2020 (p = 0.025). MPEs were adopted in 16% of for-profit trials versus 4% of non-profit trials (p = 0.006). The proportion of trials adopting MPEs was particularly high with immunotherapy (53%, p < 0.00001). Out of 27 trials with MPEs, 10 (37%) adopted an explicit definition of 'co-primary' endpoints, but only 1/10 declared the positivity of both endpoints critical for interpretation. Most trials (23, 85%) planned correction for multiplicity. Of 21 publications with positive conclusions, only 12 had a statistically significant positive result in both primary endpoints. In four cases (15%), positive conclusions were based on PFS results alone. CONCLUSIONS: Adoption of MPEs in randomised trials in oncology is quite common. Only a minority of trials respect recommendations by regulatory agencies about the adoption of MPEs, definition of 'co-primary' endpoints and correction for multiplicity.

Performing oncological procedures during COVID-19 outbreak: a picture from an Italian cancer center.

Aim: Since SARS-CoV-2 infection rapidly spread around the world, Italy has quickly become one of the most affected countries. Healthcare systems introduced strict infection control measures to ensure optimal care, especially in frail groups such as cancer patients (pts). This study investigated the efficacy of SARS-CoV-2 pre-procedure screening and whether COVID-19 influenced timely diagnosis and therapy. Methods: Data of oncological procedures of pts with confirmed or suspected cancer diagnosis, treated at Oncology Department or coming from Emergency Department of San Luigi Gonzaga Hospital between June 2020 and March 2021 were retrospectively collected. A nasopharyngeal swab (NPS) was performed in outpatients 24/48 h before procedures. Inpatients were tested by NPS before and after hospitalization. Results: Two hundred and twenty-one pts were included in this analysis. Median age was 73 years, males were 58%. Eastern Cooperative Oncology Group (ECOG) Performance Status was 0 or 1 in 88% of pts. The most frequent cancer type was lung cancer (57%). Stages IV were 77%. Two hundred and forty-three scheduled procedures were performed with diagnostic (n: 142; 58%), therapeutic (n: 55; 23%), and palliative (n: 46; 19%) intent. One hundred and four and 139 procedures were performed in out- and in-pts, respectively. Of the 234 NPS performed, 10 (4%) were positive. Two pts were infected during hospitalization, 8 in community. Most of them were asymptomatic, while only 2 had mild symptoms. Eight procedures (3%) were postponed, 1 cancelled, while 2 were performed in positive pts. Median time to resolution of the infection was 17 days (11-36). Median delay in the procedures was 25 days (14-55). Five pts started systemic treatment, after a median time of 37.5 days (13-57). Conclusions: SARS-CoV-2 infection led to the postponement of a small, but not negligible percentage of oncological procedures. However, the low infection rate observed suggests that structured screening for COVID-19 is critical for the best management of scheduled procedures during pandemic.

Italian survey on the clinical management of non-small cell lung cancer patients during the COVID-19 pandemic: A lesson for the second wave.

This study investigated the clinical management of non small cell lung cancer (NSCLC) patients during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Italy. A 29-questions survey was sent to 95 Italian thoracic oncologists, with 77 % of them declaring significant changes in the outpatients management and treatment. The results of this survey pointed out a significant delay of lung cancer diagnosis along with a relevant reduction of patients' accrual within clinical trials. Telemedicine emerged as a valid support for patient-healthcare interactions. Therapeutic indications followed the guidelines for adjuvant chemotherapy and concurrent chemo-radiation. Clinical indications to first-line therapies were largely confirmed, while major changes regarded the selection of second line treatment options as well as the management of elderly population. This work may represent a valid source of information to improve the clinical management of NSCLC patients during second wave of COVID-19 pandemic.

Impact of adoption of patient-reported outcomes in clinical practice on the accuracy of symptom reporting in medical records of cancer patients.

PURPOSE: Medical records are a relevant source for real-world evidence. We introduced patient-reported outcomes (PROs) in clinical practice, demonstrating a significant quality-of-life improvement, compared to usual visit. In this secondary analysis, we describe the agreement between patients' and physicians' reports of 5 symptoms. Our hypothesis was that adoption of PROs questionnaire could significantly improve the agreement. METHODS: Eligible patients were receiving active anti-cancer treatment. Patients in the control group underwent usual visits (group A), while patients of group B, before each visit, filled a PROs paper questionnaire, to provide information about symptoms and toxicities. No specific instructions were provided to physicians to integrate such information in medical records. Agreement between patient and physician evaluations was assessed by Cohen's κ, calculating under-reporting as proportion of toxicities reported by patients but not recorded by physicians. RESULTS: 211 patients (412 visits) have been analyzed. For all symptoms, Cohen's κ was better for group B: emesis (0.25 group A vs. 0.36 group B), diarrhea (0.16 vs. 0.57), constipation (0.07 vs. 0.28), pain (0.22 vs. 0.42), fatigue (0.03 vs. 0.08). For all symptoms, although under-reporting was relevant in both groups, it was lower for group B: emesis (75.49% vs. 60.0%, p=0.031), diarrhea (82.89% vs. 50.0%, p<0.001), constipation (92.11% vs. 69.57%, p<0.001), pain (59.57% vs. 42.31%, p=0.01), fatigue (82.11% vs. 64.10%, p<0.001). CONCLUSION: Adoption of paper PROs allowed a significant reduction in under-reporting of symptoms, but agreement remained suboptimal. Direct integration of electronic PROs could minimize the issue of under-reporting of medical records, increasing their accuracy.

Chemotherapy in non-small cell lung cancer patients after prior immunotherapy: The multicenter retrospective CLARITY study.

OBJECTIVES: In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of "druggable" mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. MATERIALS AND METHODS: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. RESULTS: In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5-8.1), median PFS of 4.1 months (95 % CI 3.4-4.8) and ORR of 22.8 %. A "Post-CKI score" was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59-0.71). CONCLUSIONS: Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The "Post-CKI score" was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.

SARS-CoV-2 Infection in Cancer Patients: A Picture of an Italian Onco-Covid Unit.

Background: The world, and Italy on the front lines, has experienced a major medical emergency due to the novel coronavirus outbreak. Cancer patients are one of the potentially most vulnerable cohorts of people, but data about their management are still few. Patients and Methods: In this monocentric retrospective study we included all SARS-CoV-2 oncological patients accepted, between March 27th and April 19th 2020, at the Onco-COVID Unit at San Luigi Gonzaga Hospital, one of the few Italian oncological-COVID wards. Data were obtained from medical records. Results: Eighteen cancer patients with COVID-19 were included. The mean (±SD) age of patients was 67 ± 14 years, 89% were men. Seven (39%) developed infection in communities and 11 (61%) during hospitalization. Lung cancer was the most frequent type of cancer (10, 56%). Seven patients (39%) were symptomatic for COVID-19 at the time of diagnosis and symptoms began 2 (±2) days before. The most common were shortness of breath and diarrhea. Fever was present in 5 patients (28%). Among the 11 asymptomatic patients, 8 (73%) became symptomatic during the hospitalization (mean time of symptoms onset 4 days ±4). Six patients (33%) were on active anti-tumor treatment: 2 (33%) received anti-tumor therapy within 2 weeks before the infection diagnosis and 2 (33%) continued oncological treatment after SARS-CoV-2 positivity. Eight (44%) patients died within a mean of 12 days (±8) from the infection diagnosis. Conclusions: Our series confirms the high mortality among cancer patients with COVID-19. The presence of asymptomatic cases evidences that typical symptoms and fever are not the only parameters to suspect the infection. The Onco-Covid unit suggests the importance of a tailored and holistic approach, even in this difficult situation.

The MIMIC Study: Prognostic Role and Cutoff Definition of Monocyte-to-Lymphocyte Ratio and Lactate Dehydrogenase Levels in Metastatic Colorectal Cancer.

BACKGROUND: Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). MATERIAL AND METHODS: This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR-LDH combined (group 1: MLR-LDH low; group 2: MLR or LDH high; group 3: MLR-LDH high). The second cohort was used to validate the model. RESULTS: At the median follow-up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39-4.04), high LDH (HR, 1.73; 95% C.I., 1.03-2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62-4.66), and group 3 (HR, 3.73; 95% C.I., 1.94-7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. CONCLUSION: MLR and LDH are circulating cost-effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC. IMPLICATIONS FOR PRACTICE: High monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels could be a sign of a tumor's recruitment of suppressive and inflammatory cells worsening prognosis of different types of cancer, including colorectal cancer (CRC). Currently, no data are available for metastatic CRC regarding a cutoff definition for MLR or the prognostic impact of MLR and MLR-LDH combined. The present study showed in the training cohort and confirmed in the validation and whole cohort that MLR is a reliable and independent laboratory biomarker, which is easy to use, to predict clinical outcomes in patients with mCRC. Moreover, MLR and composite MLR-LDH could potentially result in an incremental improvement in the prognostic value of these biomarkers, being used as stratification tools for patients with mCRC.

The role of patient-reported outcomes in outpatients receiving active anti-cancer treatment: impact on patients' quality of life.

INTRODUCTION: Patient-reported outcomes (PROs) are the gold standard to describe subjective symptoms. Nurses can be successfully involved in collecting symptom information, because of their direct relationship with the patient. In order to improve clinical management of outpatients receiving active anti-cancer treatment, we introduced in routine clinical practice an assessment of patient-reported symptoms and toxicities, starting from January 2018. Our hypothesis was that this could help to better control symptoms, improving patients' quality of life (QoL). METHODS: Eligible patients were receiving an active anti-cancer treatment, as outpatients. Patients included in the control group (treated in 2017) underwent "usual" visits (group A), while patients treated in 2018, before each visit received a questionnaire by a dedicated nurse, in order to provide information about symptoms and toxicities (group B). Primary objective was the comparison of QoL changes, measured by EORTC QLQ-C30. RESULTS: A total of 211 patients have been analyzed (119 group A; 92 group B). After 1 month, mean change from baseline of global QoL was - 1.68 in group A and + 2.54 in group B (p = 0.004, effect size 0.20). Group B showed significantly better mean changes for fatigue, pain, and appetite loss. Proportion of patients obtaining a clinically significant improvement in global QoL score was higher in group B (32.6%) compared to group A (19.3%, p = 0.04). Patients' satisfaction with questionnaire was high. CONCLUSION: Introduction of PROs in clinical practice, thanks to an active role of nurses, was feasible, produced high patients' satisfaction and a significant QoL improvement, compared to the traditional modality of visit.