Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study.

The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence.

Preoperative Prognostic Nutritional Index was not predictive of short-term complications after laparoscopic resection for rectal cancer.

BACKGROUND AND AIM: Prognostic Nutritional Index (PNI) is a useful tool to predict short-term results in patients undergoing surgery for gastrointestinal cancer. Few studies have addressed this issue in colorectal cancer or specifically in rectal cancer. We evaluated the prognostic relevance of preoperative PNI on morbidity of patients undergoing laparoscopic curative resection for rectal cancer (LCRRC). METHODS: PNI data and clinico-pathological characteristics of LCRRC patients (June 2005-December 2020) were evaluated. Patients with metastatic disease were excluded. Postoperative complications were evaluated using the Clavien-Dindo classification. RESULTS: A total of 182 patients were included in the analysis. Median preoperative PNI was 36.5 (IQR 32.8-41.2). Lower PNI was associated with females (p=0.02), older patients (p=0.0002), comorbidity status (p<0.0001), and those who did not receive neoadjuvant treatment (p=0.01). Post-operative complications occurred in 53 patients (29.1%), by the Clavien-Dindo classification: 40 grades I-II and 13 grades III-V. Median preoperative PNI was 35.0 (31.8-40.0) in complicated patients and 37.0 (33.0-41.5) in uncomplicated patients (p=0.09). PNI showed poor discriminative performance regarding postoperative morbidity (AUC 0.57) and was not associated with postoperative morbidity (OR 0.97) at multivariable analysis. CONCLUSIONS: Preoperative PNI was not associated with postoperative morbidity after LCRRC. Further research should focus on different nutritional indicators or hematological/immunological biomarkers.

Prognostic effect of sarcopenia in patients undergoing laparoscopic rectal cancer resection.

BACKGROUND: The importance of body composition, in particular skeletal muscle mass, as risk factor affecting survival of cancer patients has recently gained increasing attention. The relationship between sarcopenia and oncological outcomes has become a topic of research in particular in patients with gastrointestinal cancer. However, there are few studies addressing this issue in colorectal cancer, and even less specifically focused on rectal cancer, in particular in Western countries. The aim of this study was to evaluate the prognostic relevance of preoperative skeletal mass index (SMI) on long-term outcomes in patients undergoing laparoscopic curative resection for rectal cancer. METHODS: SMI data and clinicopathological characteristics of rectal cancer patients in a 15-year period (June 2005-December 2020) were evaluated; patients with metastatic disease at surgery were excluded; overall and disease-free survival as well as recurrence were evaluated. RESULTS: Hundred and sixty-five patients were included in the study. Sarcopenia was identified in 30 (18%) patients. Multivariate analysis identified sarcopenia (HR = 3.28, CI = 1.33-8.11, P = 0.015), along with age (HR = 1.06, CI = 1.02-1.10, P = 0.002) and stage III (HR = 2.63, CI = 1.13-6.08, P < 0.03) as independent risk factors for overall survival. CONCLUSION: Long-term results of rectal cancer patients undergoing curative resection are affected by their preoperative skeletal muscle status. Larger studies including comprehensive data on muscle strength along with SMI are awaited to confirm these results on both Eastern and Western rectal cancer patient populations before strategies to reverse muscle depletion can be extensively applied.

Does 3D laparoscopic video technology affect long-term survival in right hemicolectomy for cancer compared to standard 2D? A propensity score study.

BACKGROUND: There are few studies focused on the short-term results of laparoscopic right hemicolectomy performed with 2D (two-dimension) or 3D (three-dimension) video technology and none on the oncologic effects. The aim of the study was to assess the long-term results of laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis using 3D or 2D video in patients with right colon cancer with at least three years of oncologic follow-up. METHODS: Data from patients undergoing laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis for cancer in an 11-year period (June 2008-June 2019) and ≥ 3 years of follow-up were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons. RESULTS: 111 patients were included in the study: 56 (50.5%) in the 3D group and 55 (49.5%) in the 2D group. Tumor stage and number of lymph nodes harvested were similar. Overall and disease-free survival were not different in the two groups. Local recurrence occurred in none of the patients, and distant metachronous metastases were similar in the two groups. A propensity score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. CONCLUSIONS: Laparoscopic 3D technology allows similar oncological results as 2D vision in LRH with intracorporeal anastomosis. Larger prospective randomized studies might confirm these results in the long-term follow-up.

Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.

BACKGROUND: Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). MATERIALS AND METHODS: We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. RESULTS: One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. CONCLUSION: We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. IMPLICATIONS FOR PRACTICE: This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.

Impact of influenza syndrome and flu vaccine on survival of cancer patients during immunotherapy in the INVIDIa study.

Aim: INVIDIa was a retrospective, multicenter study, exploring the clinical efficacy of influenza vaccine in 300 cancer patients undergoing immunotherapy. Overall survival (OS) was immature at the initial report. Methods: We reported the final OS analysis from the original study population and within subgroups. Results: Both at the univariate and multivariate analysis, the occurrence of influenza syndrome (IS) was significantly related to better OS in the overall population (OR: 0.53 [95% CI: 0.32-0.88]; p = 0.01). In the lung cancer subgroup, receiving flu vaccine and/or developing IS was related to better OS (p = 0.04). Within elderly patients, the flu vaccine was the main variable for the relative OS advantage (p = 0.05). Conclusion: Receiving the flu vaccine and/or developing IS was related to better OS within the INVIDIa population.

Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.

Results From a Large, Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region.

BACKGROUND: Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting. PATIENTS AND METHODS: We conducted a multicenter retrospective analysis in the Triveneto region of Italy. RESULTS: One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia. CONCLUSION: This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.

Predictive role of changes in the tumor burden and International Metastatic Renal Cell Carcinoma Database Consortium class during active surveillance for metastatic renal cell carcinoma.

BACKGROUND: Despite important results achieved for metastatic renal cell carcinoma, some patients could benefit from local treatments or an initial active surveillance (AS) period for recurrent disease. We aim to analyze: changes in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, the number of metastases and the disease burden from the start of AS to the beginning of systemic therapy; and if these changes influenced patient outcomes. PATIENTS AND METHODS: Patients who started AS at our institution from January 2007 to April 2016 were included. The Kaplan-Meier method was used to estimate total overall survival (tOS) and progression-free survival. Changes in IMDC class, number of metastatic sites, and tumor burden (TB) were evaluated and related to patient survival. Among the patients who started active treatment, progression-free survival and post surveillance OS (psOS) were evaluated. RESULTS: 52 patients were included in the analysis. Median time on AS and tOS were 18.3 and 80.1 months respectively. Baseline factors were not related to the time on AS apart from the IMDC classification (HR = 2.15; 95% CI: 1.19-3.87; P = 0.011). The increase in the number of metastatic sites during AS was correlated with poor tOS (HR = 2.86; 95% CI: 1.29-6.34; P = 0.010). The increase of the TB was a negative prognosis factor for tOS (HR = 1.16; 95% CI: 1.02-1.31; P = 0.024) and psOS (HR = 1.21; 95% CI: 1.07-1.40; P = 0.004). Both IMDC class and change in the TB at the start of therapy were related to psOS. The retrospective nature and the lack of an external review of the imaging are its main limitations. CONCLUSIONS: During AS, patients rarely experience a deterioration of their IMDC prognostic class, and the change in the TB, more than the increase in the number of metastatic sites, may help physicians to make decisions about the early termination of AS and the start of systemic therapy.

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study.

AIM: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. METHODS: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. RESULTS: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. CONCLUSION: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy.

Enzalutamide after chemotherapy in advanced castration-resistant prostate cancer: the Italian Named Patient Program.

AIM: To collect efficacy and safety data of enzalutamide after docetaxel, we retrospectively evaluated the Italian Named Patient Program results. PATIENTS & METHODS: Two hundred and nine metastatic castration-resistant prostate cancer patients were enrolled. Median age was 73 years. Total 42.1% patients had pain, 14.4% had a performance status of two and 59.8% had a Gleason score ≥8. Total 31.1% had previously received ≥2 chemotherapies, 15.3 and 12% had been previously treated with abiraterone and cabazitaxel, respectively and 14.8% had received both. RESULTS:  Median progression-free survival and overall survival were 4.8 and 13.1 months, respectively. A prostate-specific antigen reduction ≥50% was observed in 49.1%. Total 32.7% abiraterone-pretreated patients achieved a biochemical response compared with 56% of abiraterone-naive patients. CONCLUSION:  Enzalutamide was safe and well tolerated. Its antitumor activity in abiraterone-pretreated patients was limited.

Is It Possible to Improve Prognostic Classification in Patients Affected by Metastatic Renal Cell Carcinoma With an Intermediate or Poor Prognosis?

BACKGROUND: The International mRCC (metastatic renal cell carcinoma) Database Consortium (IMDC) is the standard classification for mRCC. We aimed to evaluate the outcomes of a large cohort of patients with an intermediate or a poor prognosis treated with sunitinib using a different cutoff point for IMDC to improve the classification. PATIENTS AND METHODS: Patients with an intermediate or a poor prognosis according to the IMDC criteria and treated with sunitinib were included in the present study. A new cutoff point was used to categorize the patients. The new score was validated in an independent cohort of patients. RESULTS: A total of 457 patients were included in the present study. Significant differences in overall survival (OS) were highlighted regarding the number of prognostic factors. Three categories were identified according to the presence of 1 (ie, favorable-intermediate group), 2 (ie, real-intermediate group), and > 2 (ie, poor group) factors. The corresponding median OS periods were 32.9, 20.0, and 8.9 months, with significant differences among the groups. The validation cohort included 389 patients. The median OS period for the favorable-intermediate group, real-intermediate group, and poor group was 34.3, 19.4, and 9.0 months, respectively, with confirmed significant differences among the groups. CONCLUSION: Our analysis revealed significant differences among patients with an intermediate prognosis using the IMDC prognostic factors. Further investigations to optimize the use of available and upcoming therapies are required.

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study.

BACKGROUND: Ramucirumab-alone or combined with paclitaxel-represents one of the main options for patients failing first-line treatment for advanced gastric cancer. OBJECTIVE: The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the "real-life setting". PATIENTS AND METHODS: Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m2 i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: One hundred sixty-seven patients with disease progression on first-line therapy received ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median treatment duration was 4 months (1-17 months). Global incidence of grade (G) 3-4 toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to toxicity in 3% of patients. The most frequent adverse events (AE) were G1-2 fatigue (27.5%), G1-2 neuropathy (26.3%), and G1-2 neutropenia (14.9%). ORR was 20.2%. Stable disease was observed in 39.2% of patients, with a disease control rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months (95% confidence interval [CI] 4.1-4.7), whereas median OS was 8.0 months (95% CI: 7.09-8.9). In a multivariate analysis, ECOG performance status <1 or ≥1 (HR 1.13, 95% CI 1.0-1.27, p = 0.04) and the presence versus absence of peritoneal metastases (HR 1.57, 95% CI 1.63-2.39, p = 0.03) were independent poor prognostic factors. CONCLUSIONS: These "real-life" efficacy data on ramucirumab treatment are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.

Next-generation repeat-free FISH probes for DNA amplification in glioblastoma in vivo: Improving patient selection to MDM2-targeted inhibitors.

A next-generation FISH probe mapping to the MDM2 locus-specific region has recently been designed. The level of MDM2 gene amplification (high versus low) may allow selection of patients for cancer treatment with MDM2 inhibitors and may predict their responsiveness. We investigated the spectrum of MDM2 gene alterations using the new probes in vivo after visualizing single neoplastic cells in situ from a series of glioblastomas. Signals from next-generation repeat-free FISH interphase probes were identified in tissue microarrays that included 3 spots for each of the 48 cases. The murine double minutes (MDM2)-specific DNA probe and the satellite enumeration probe for chromosome 12 were used. Three cases (6%) showed more than 25 signals (high gene amplification), and 7 (15%) showed 3-10 signals (gains); among these, 4 cases (8%) had an equal number of MDM2 and centromeric signals on chromosome 12 (polyploidy). Genomic heterogeneity was observed only in 3 cases with low gene amplification. In our series, 6% of glioblastomas exhibited high MDM2 amplification (in vivo) with a pattern related to the known double minutes/chromothripsis phenomenon (in situ), and only cases with low amplification showed genomic heterogeneity. We concluded that the rate of MDM2 gene amplification can be a useful predictive biomarker to improve patient selection.

Cathepsin K expression in castration-resistant prostate carcinoma: a therapeutical target for patients at risk for bone metastases.

BACKGROUND: The lysosomal cysteine protease cathepsin K is involved in bone remodeling and is also expressed in the peritumoral stroma of carcinomas arising from different organs. A new generation of cathepsin K inhibitors blocking the RANKL/RANK pathway are being developed. We sought to investigate cathepsin K expression in a cohort of castration-resistant prostate carcinomas. METHODS: Sixteen cases of castration-resistant disease with at least 5 years of follow-up were selected from a cohort of 280 patients who underwent surgery. Cathepsin K was evaluated on formalin-fixed and paraffin-embedded tissue microarrays with 5 tissue spots per case. These were scored as high 2+ (≥30% of cells), low 1+ (<30% of cells) or zero (absence), distinguishing tumor cells and peritumoral stroma cells. Low (1+) and absence (0) of scoring were interpreted as negative, and high (2+) as positive. RESULTS: The castration-resistant group was composed of 15 acinar adenocarcinomas and 1 neuroendocrine carcinoma, and all showed at least Gleason score 8 at prostatectomy. Two out of 16 cases (12%) scored positive for cathepsin K in tumor cells; and 5 of 16 cases (31%) scored positive in peritumoral stroma cells. The neuroendocrine and acinar subtypes of carcinoma with positive immunoexpression in neoplastic cells developed bone metastases after 4 and 5 years, respectively, and subsequently died. CONCLUSIONS: Patients affected by castration-resistant prostate carcinoma may be tested for cathepsin K, and a positive strong expression (2+) could be a useful predictive biomarker of response to targeted agents, aiding in the selection of patients eligible for these treatments.

First-Line PAzopanib in NOn-clear-cell Renal cArcinoMA: The Italian Retrospective Multicenter PANORAMA Study.

INTRODUCTION: Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients. PATIENTS AND METHODS: Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed. Response rate, progression-free survival (PFS), and overall survival (OS) were evaluated. Univariate and descriptive analyses were performed. RESULTS: Thirty-seven patients with nccRCC were treated with first-line pazopanib; 51% had papillary histology, 24% chromophobe, 22% unclassified, and 3% had Xp11.2 translocation. Dose reductions/temporary interruptions for toxicity were required in 46% of cases. Grade (G) 3/4 toxicity was seen in 32%, G1/2 in 89% of cases; 81% achieved disease control, with 10 partial responses (27%) and 20 cases of stable disease (54%); 16% of patients had disease progression as best response. Median PFS and OS were 15.9 and 17.3 months, respectively. In univariate analysis, nephrectomy (P = .020), Memorial Sloan Kettering Cancer Center (MSKCC) score (P < .001), basal neutrophil/lymphocyte ratio (NLR; P = .009) and performance status (PS) (P = .001) were associated with PFS; MSKCC score (P < .001), International Metastatic Renal Cell Carcinoma Database Consortium score (P = .003), PS (P < .0001), nephrectomy (P = .002), histology (P = .035), dose reductions/interruptions (P = .039), best response to treatment (P < .001), and NLR (P = .008) were associated with OS. CONCLUSION: In nccRCC patients, treatment with pazopanib was effective and feasible; dose reductions required for toxicity were similar as expected in ccRCC.

Reprofiling Metastatic Samples for Chromosome 9p and 14q Aberrations as a Strategy to Overcome Tumor Heterogeneity in Clear-cell Renal Cell Carcinoma.

Losses of chromosomes 9p and 14q are associated with worse outcomes in patients affected by clear-cell renal cell carcinoma (RCC) and are helpful for prognostic risk stratification. Both chromosomal loci harbor several hot-spot molecular pathways suitable for targeted therapeutic interventions. Intratumor heterogeneity may foster tumor adaptation and therapeutic failure. We sought to investigate the presence of losses of the hot spots of chromosomal loci 9p and 14q in primary clear-cell RCC and matched metastatic tissues. CD10 and CD13 were performed on 7 cases of clear-cell RCC with hematogenous tissue metastases. Cytogenetic fluorescence in situ hybridization analysis was performed on primary and matched metastatic tissues using specific probes mapping the 9p and the 14q loci. The loss of chromosome 9p was observed in 85% of both primary clear-cell RCCs and in matched metastases; 14% showed discordance between primary and matched metastases showing gains. The loss of chromosome 14q was observed in 58% of both primary and matched metastases. Only 3/7 (42%) did show an equal status of loss of chromosome 14q. Heterogeneity of the cytogenetic status between metastatic and primary clear-cell RCCs is observed for the loss of chromosome 14q rather than chromosome 9p. The impact of chromosome 14q cytogenetic status, harboring the HIF1 gene, a major driver for the angiogenenic switch, may drive the efficacy of targeted inhibitors, whereas the loss of chromosome 9p, harboring other hot-spot genes, seems to be related to the metastatic behavior per se, without cytogenetic modulation. Reprofiling the metastatic tissue, as compared with the primary tumor, in patients affected by metastatic RCC could be a novel approach to overcome resistance to VEGF(Rs)-targeting agents.

Systemic immune-inflammation index predicts the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib.

BACKGROUND: In this retrospective analysis, we explored the prognostic and predictive value of the systemic immune-inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, at baseline and changes at week 6 during first-line sunitinib in patients with metastatic renal cell cancer (RCC). RESULTS: Patients were stratified into high SII (≥ 730) and low SII (< 730) groups. SII was associated with objective response, p < 0.0001. The median PFS was 6.3 months (95% CI 5.5-8.9) in patients with SII ≥ 730 and 18.7 months (95% CI 14.7-22.8) in those with SII < 730, p < 0.0001. The median OS was 43.6 months (95% CI 35.3-52.1) in patients with SII < 730, and 13.5 months (95% CI 9.8-18.5) in those with SII ≥ 730, p < 0.0001. In multivariate analysis, performance status, IMDC score and SII were able to predict OS (HR = 3.29, HR = 1.71 and HR = 1.79, respectively). MATERIALS AND METHODS: We included 335 consecutive RCC patients treated with first-line sunitinib. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion at week 6 of treatment on PFS and OS was evaluated by Cox regression analyses. CONCLUSIONS: The SII and its changes during treatment represent a powerful prognostic indicator of clinical outcome in patients with metastatic RCC.