Assessment of the psychosocial and economic impact according to sex in non-small cell lung cancer patients: an exploratory longitudinal study

Background: Little is known about the impact of sex on lung cancer patients from the psychological, economic and social perspectives. This study was designed to explore the psychosocial and economic impact according to sex of metastatic non-small cell lung cancer (mNSCLC) in patients and caregivers. Methods: Exploratory study of two cohorts of patients starting first-line treatment for mNSCLC. The following questionnaires were administered at baseline, 4 months later and following the first and second disease progression: APGAR, relationship impact scale, DUKE-UNC scale, economic impact in patients and caregiver, and Zarit scale. It was planned to include 1250 patients to get an 80% possibility of detecting as significant (p < 0.05) effect sizes less than 0.19 between men and women. Univariate comparisons were made between the tests applied to men and women. Overall survival was estimated with Kaplan–Meier method. Cox analyses were done to estimate hazard ratios (HRs) with 95% CI. Results: 333 patients were included. Most families reported to continue being functional despite the lung cancer diagnosis. Regardless of sex, they did not perceive changes in their partner relationship. Most patients felt their social support was normal. Roughly 25% of people reported a worsening in their economic situation, without remarkable differences by sex. Statistically significant differences were found between both groups regarding the caregiver’s relationship to the patient (more parents were the caregiver in females than in males, p < 0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p < 0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden. Conclusions: This study provides a preliminary insight into sex-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a sex perspective. Nevertheless, due to the low recruitment rate and the relevant loss of patients during the follow-up, it was difficult to find differences by sex. Trial registration: ClinicalTrials.gov identifier: NCT02336061. Ethics committee: Comité Ético de Investigación Clínica del Hospital Clínic de Barcelona, Spain. Reference number: HCB/2014/0705

Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-{alpha} as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population

BACKGROUND: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-alpha) treatment in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-alpha (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included. RESULTS: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values. CONCLUSIONS: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-alpha

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Randomised Phase II study comparing alternating cycles of sunitinib and everolimus vs standard sequential administration in first-line metastatic renal carcinoma (SUNRISES study)

Objective: To investigate the efficacy of alternating cycles of sunitinib and everolimus vs standard sequential treatment of sunitinib followed by everolimus in first-line metastatic renal cell carcinoma (mRCC), as alternating blockade of vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR) pathways could potentially prevent the occurrence of resistance to anti-VEGFR therapy in mRCC. Patients and Methods: SUNRISES, a randomised open-label Phase II study, investigated the efficacy of alternating cycles of sunitinib and everolimus vs standard sequential treatment of sunitinib followed by everolimus upon progression. Treatment-naïve patients with clear-cell mRCC were included. Alternating treatment consisted on 12 weeks of sunitinib, followed by 12 weeks of everolimus. The primary endpoint was the progression-free survival (PFS) rate at 1 year. The secondary endpoints included the median PFS, overall survival (OS), response rate, and safety. Results: Accrual was low due to the advent of new-generation therapies, and the study was stopped prematurely. Only 41 patients out of the planned 102 patients were accrued, and randomised in a 2:1 ratio (15 patients to the control arm, 26 to the experimental arm). In all, 60.9% of patients had performance status (PS) 0 and 39% PS 1; 63% had a favourable prognostic risk profile, while 36% were intermediate risk. The primary endpoint was not met. The 1-year PFS rate was 49.7% (experimental arm) vs 84.62% (control arm; P = 0.11). There was a trend towards fewer Grade ≥3 adverse events with the alternating approach (50% vs 73.3%; P = 0.14). The median OS was similar in both treatment arms. The other secondary endpoints favoured the control arm. Conclusions: The study failed to show any benefit of alternating cycles of sunitinib and everolimus in patients with mRCC. The alternating approach using an mTOR inhibitor does not seem to prevent the occurrence of resistance to VEGFR blockade. © 2020 The Authors BJU International © 2020 BJU International Published by John Wiley &amp; Sons Lt

Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-{alpha} as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population

BACKGROUND: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-alpha) treatment in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-alpha (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included. RESULTS: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values. CONCLUSIONS: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-alpha

SEOM clinical guideline for the management of malignant melanoma (2017)

All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy. Up to 10 years follow up is reasonable for melanoma patients with dermatologic examinations and physical exams

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma : the ROSING Study

Altres ajuts: Funding for this study was provided bythe iLUNG Program (B2017/BMD-3884) from the Comunidad de Madrid.Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm