Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Sexual dysfunctions in breast cancer patients: evidence in context.

INTRODUCTION: In breast cancer patients, endocrine therapy may exert a negative impact on sexual functioning in both genders, with potentially relevant consequences concerning quality of life and treatment adherence. The availability of effective interventions to maintain and/or restore sexual health in breast cancer patients is a key issue to a research agenda. OBJECTIVES: To summarize and critically discuss the most updated and qualitatively relevant literature on the therapeutic approach to sexual impairment in breast cancer patients, with a focus on patients treated with endocrine therapy. METHODS: We searched PubMed from its inception to February 2022 for observational and intervention trials including participants with sexual dysfunctions. We were particularly interested in studies of breast cancer patients with sexual dysfunctions while undergoing endocrine therapy. We developed a search strategy with the aim of maximizing the number of articles considered for screening and potential inclusion. RESULTS: Forty-five studies were selected: 3 observational and 42 intervention studies. Thirty-five studies were exclusively focused on female breast cancer populations. We could not identify studies exclusively focused on or also including male breast cancer patients. Overall, in female patients, the available armamentarium encompasses vaginal lubricants, moisturizers, estrogens, dehydroepiandrosterone, CO2 laser, ospemifene, and counseling. None of these interventions has been demonstrated to completely solve sexual dysfunctions when singularly considered. More favorable outcomes have come from the combination of different therapies. CONCLUSION: In female breast cancer, future research is oriented toward the gain of evidence on combined therapies and long-term data on safety issues on the most promising interventions. The lack of evidence on sexual disturbances in male breast cancer patients remains a major concern.

Observational Multicenter Study on the Prognostic Relevance of Coagulation Activation in Risk Assessment and Stratification in Locally Advanced Breast Cancer. Outline of the ARIAS Trial.

A hypercoagulable state may either underlie or frankly accompany cancer disease at its onset or emerge in course of cancer development. Whichever the case, hypercoagulation may severely limit administration of cancer therapies, impose integrative supporting treatments and finally have an impact on prognosis. Within a flourishing research pipeline, a recent study of stage I-IIA breast cancer patients has allowed the development of a prognostic model including biomarkers of coagulation activation, which efficiently stratified prognosis of patients in the study cohort. We are now validating our risk assessment tool in an independent cohort of 108 patients with locally advanced breast cancer with indication to neo-adjuvant therapy followed by breast surgery. Within this study population, we will use our tool for risk assessment and stratification in reference to 1. pathologic complete response rate at definitive surgery, intended as our primary endpoint, and 2. rate of thromboembolic events, intended as our secondary endpoint. Patients' screening and enrollment procedures are currently in place. The trial will be shortly enriched by experimental tasks centered on next-generation sequencing techniques for identifying additional molecular targets of treatments which may integrate current standards of therapy in high-risk patients.

Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine. Real-world evidence.

Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5-24.9, 25-29.9, and 30.0-34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p = .15), while BMI ≥ 30 was associated with worse OS (p = .003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p = .001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p = .03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile.

Eribulin in Triple Negative Metastatic Breast Cancer: Critic Interpretation of Current Evidence and Projection for Future Scenarios.

Triple negative breast cancer (TNBC) is characterized by distinctive biological features that confer an aggressive clinical behavior. In TNBC patients, the absence of well-defined driver pathways such as hormonal receptor expression or hyperactivation of the human epidermal growth factor receptor 2 (HER2) significantly reduce the spectrum of therapeutic options, which are currently mainly confined to chemotherapy. Thus far, median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. However, the heterogeneity recently revealed at a gene expression level inside the TNBC family may help inform therapeutic decisions concerning the use of chemotherapy and hopefully lead the way to novel targeted options that include immunotherapy. Eribulin, a halichondrin class antineoplastic drug, is currently recommended for treatment of HER2 negative metastatic or recurrent breast cancer (BC) previously exposed to anthracyclines and taxanes, also for patients with a TNBC. It is currently indicated from the second line of treatment. In this review, we aim to analyze a wide range of cumulated evidence on eribulin use in TNBC including preclinical studies, intervention and observational clinical trials. Data from the real-world setting and the emerging evidence increasingly substantiating the rationale for combinations with new generation treatment strategies, e.g., PARP-inhibitors, immune checkpoint inhibitors, will be also discussed.

Cervical lymphadenopathy: can the histogram analysis of apparent diffusion coefficient help to differentiate between lymphoma and squamous cell carcinoma in patients with unknown clinical primary tumor?

PURPOSE: To retrospectively evaluate the value of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck nodes. METHODS: A total of 39 patients, 20 affected by lymphoma and 19 affected by metastatic non-nasopharyngeal SCC, were included in this retrospective study. All patients underwent MR imaging with a 1.5 T scanner system, including diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and 800 s/mm2). The entire tumor volume was manually delineated on the ADC maps, using the T2-weighted images and DWIs with b = 800 s/mm2 as a guide to the lesion location. The Mann-Whitney rank-sum test for independent samples was performed to compare the histogram parameters of patients with lymphoma and SCC. RESULTS: The SCCs showed significantly higher median ADC (ADCmedian) and mean ADC (ADCmean) values, compared to lymphomas (p < 0.001), while they exhibited lower kurtosis and skewness without reaching significance (p = 0.066 and 0.148, respectively). The ADCmean and ADCmedian had the best discriminative powers for differentiating lymphoma and SCC, with an area under the curve of 87% and 85%, respectively. The optimal cutoff values for ADCmean and ADCmedian as predictors for lymphoma were ≤ 0.83 × 10-3 mm2/s and ≤ 0.73 × 10-3 mm2/s, respectively. CONCLUSIONS: The whole-lesion ADC histogram analysis of cervical lymphadenopathy may help to discriminate lymphomas from non-nasopharyngeal SCC in patients with unknown clinical primary tumor.

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience.

Data from 423 human epidermal growth factor receptor 2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6-35.4) and clinical benefit was 52.7% (95% CI, 48-57.5). ORR was negatively affected by prior exposure to everolimus/exemestane ( p = 0.002) and favorably influenced by early line-treatment ( p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8-16) and median overall survival was 24 months (95% CI, 17-30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2-, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.

Metabolic Determinants and Anthropometric Indicators Impact Clinical-pathological Features in Epithelial Ovarian Cancer Patients.

BACKGROUND: Over the last twenty years, the efforts of the scientific community devoted to the comprehension and treatment of ovarian cancer have remained poorly remunerative, with the case-fatality ratio of this disease remaining disappointedly high. Limited knowledge of the basic principles regulating ovarian carcinogenesis and factors impacting the course of disease may significantly impair our ability to intervene in early stages and lessen our expectations in terms of treatment outcomes. In the present study, we sought to assess whether metabolic factors and anthropometric indicators, i.e., pre-treatment fasting glucose and body mass index, are associated with renown cancer related prognostic factors such as tumour stage and grade at diagnosis. MATERIALS AND METHODS: Study participants were 147 women diagnosed with epithelial ovarian cancer and treated with platinum based regimens and/or surgery at the Regina Elena National Cancer Institute of Rome, Italy. Glucose levels were assessed at the institutional laboratories on venous blood collected in overnight fasting conditions and prior to any therapeutic procedure. Stage was coded according to the FIGO staging system based on the results of the diagnostic workup, while tumour grade was locally assessed by an expert pathologist. Participants' characteristics were descriptively analyzed for the overall study population and in a subgroup of 70 patients for whom data on body mass index (BMI) were available. FIGO stage and grade were compared by categories of pre-treatment fasting glucose defined upon the median value, i.e., 89 mg/dl. The association of interest was tested in regression models including BMI. RESULTS: For the overall study population, patients in the lowest category of fasting glucose were significantly more likely to exhibit a FIGO stage III-IV at diagnosis compared with their counterpart in the highest glucose category (81.3 vs 66.7%, p: 0.021). Subgroup analysis in 70 patients with BMI data confirmed this association (81.5 vs 55.8, p: 0.049), which remained significant when tested in regression models including BMI (OR: 0.28 95% CI 0.086-0.89, p: 0.031). No relevant evidence emerged when testing the association between fasting glucose and tumour grade. CONCLUSIONS: In patients diagnosed with epithelial ovarian cancer, pre-treatment glucose levels appear to be inversely associated with FIGO stage. Further studies are warranted to eventually confirm and correctly interpret the implications of this novel finding.

Long term efficacy and safety of Fludarabine, Cyclophosphamide and Rituximab regimen followed by (90)Y-ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma.

BACKGROUND: In this retrospective study, we investigated the efficacy and safety of radioimmunotherapy with (90)Yttrium- ibritumomab tiuxetan ((90)Y-RIT) in 9 patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete (CR) or partial remission (PR) with Fludarabine, Cyclophosphamide and Rituximab (FCR). METHODS: The median age was 63 years (range 46-77). All patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m(2)x 3 days), C (1 gr/m(2) day 1) and R (375 mg/m(2) day 4) for 4 cycles. Those who achieved at least a PR with <25 % bone marrow involvement were treated with (90)Y-RIT 11.1 or 14.8 MBq/Kg, at 3 months after completing FCR. Patients underwent a further restaging at 12 weeks after (90)Y-RIT with a total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. RESULTS: Nine patients completed the treatment: FCR followed by (90)Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR, 7 patients obtained CR and 2 PR; after (90)Y-RIT 2 patients in PR converted to CR 12 weeks later. With a median follow up of 95 months (range 20-114) since FCR and 88 months (range 13-104) since (90)Y-RIT 3 deaths were not related to lymphoma; all 3 deceased patients obtained CR before (90)Y-RIT and died still in CR. The median overall (OS) and progression free survival (PFS) have not been reached, in this analysis both OS or PFS are 67 % at 7.5 year. The most common grade 3 or 4 adverse events were hematologic. CONCLUSIONS: These results confirm the long term efficacy and safety of 4 cycles of FCR followed by (90)Y-RIT in relapsed grades 1 and 2 FL and suggest that this regimen could be a therapeutic option for this setting of patients, specially at age of 60-75 with no unexpected toxicities.

Planned neck dissection after chemoradiotherapy in advanced oropharyngeal squamous cell cancer: the role of US, MRI and FDG-PET/TC scans to assess residual neck disease.

OBJECTIVE: To investigate the ability of neck ultrasounds (US), magnetic resonance imaging (MRI) and positron emission tomography (FDG-PET/TC) in detecting residual nodal disease after chemoradiotherapy in patients with advanced oropharyngeal squamous cell carcinoma (OPSCC). METHODS: From 2006 to 2009, 36 consecutive patients affected by OPSCC with bulky nodal disease (>3 cm), treated with primary concurrent chemoradiotherapy, were enrolled prospectively. Nodal response to treatment was assessed by using US, MRI and FDG-PET/CT. Planned neck dissection (ND) was performed in all the patients, and the histopathological node status was compared to the imaging findings in order to establish sensitivity, specificity, accuracy and predictive values of each technique. RESULTS: Metastatic disease was assessed in 18/37 (48.6%) hemi-necks, always localized in levels II-IV. US showed greater sensitivity (77.8%) and, combined with FDG-PET/TC, produced the highest negative predictive value (93.3%). US, MRI and FDG-PET/TC scans showed the highest specificity (100%), accuracy (93.8%) and positive predictive values (100%). CONCLUSIONS: In the presence of advanced OPSCC with bulky nodal disease, US combined with FDG-PET/TC could be a reliable and cost-effective strategy to identify patients with complete nodal response to chemoradiotherapy that might not require post-treatment ND but only observation. When residual disease in the neck was detected, selective ND was recommended.