Psychological distress and resilience in patients with advanced cancer during the Covid-19 pandemic: the mediating role of spirituality.

BACKGROUND: The purpose of this study was to investigate the sociodemographic factors related to psychological distress, spirituality, and resilience, and to examine the mediating role of spirituality with respect to psychological distress and resilience in patients with advanced, unresectable cancer during the Covid-19 pandemic. METHODS: A prospective, cross-sectional design was adopted. Data were collected from 636 participants with advanced cancer at 15 tertiary hospitals in Spain between February 2019 and December 2021. Participants completed self-report measures: Brief Resilient Coping Scale (BRCS), Brief Symptom Inventory (BSI-18), and Spiritual well-being (FACIT-Sp). Hierarchical linear regression models were used to explore the mediating role of spirituality. RESULTS: Spirituality was significantly different according to the person's age and marital status. Psychological distress accounted for 12% of the variance in resilience (ß = - 0.32, p < 0.001) and spirituality, another 15% (ß =0.48, p < 0.001). Spirituality acted as a partial mediator in the relationship between psychological distress and resilience in individuals with advanced cancer. CONCLUSIONS: Both psychological distress and spirituality played a role in resilience in cases of advanced cancer. Spirituality can help promote subjective well-being and increased resilience in these subjects.

Immunotherapy in Advanced Prostate Cancer: Current Knowledge and Future Directions.

The advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to immunotherapy represents one of the current challenges in this clinical scenario. The management of advanced castration-resistant prostate cancer is rapidly evolving and immunotherapy treatments, mostly consisting of immune checkpoint inhibitors combinations, BiTE® (bispecific T-cell engager) immune therapies, and chimeric antigen receptors (CAR) are in development with promising results. This review analyses the current evidence of immunotherapy treatments for mCRPC, evaluating past failures and promising approaches and discussing the directions for future research.

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study.

BACKGROUND: Axitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. PATIENTS AND METHODS: Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs. disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. RESULTS: In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 vs. 26.5 months; P = .009). In LR vs. RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 vs. 10.9 months P < .001). The safety profile was manageable and consistent with known data. CONCLUSIONS: This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib.

Breast cancer patient experiences through a journey map: A qualitative study.

BACKGROUND: Breast cancer is one of the most prevalent diseases in women. Prevention and treatments have lowered mortality; nevertheless, the impact of the diagnosis and treatment continue to impact all aspects of patients' lives (physical, emotional, cognitive, social, and spiritual). OBJECTIVE: This study seeks to explore the experiences of the different stages women with breast cancer go through by means of a patient journey. METHODS: This is a qualitative study in which 21 women with breast cancer or survivors were interviewed. Participants were recruited at 9 large hospitals in Spain and intentional sampling methods were applied. Data were collected using a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data were processed by adopting a thematic analysis approach. RESULTS: The diagnosis and treatment of breast cancer entails a radical change in patients' day-to-day that linger in the mid-term. Seven stages have been defined that correspond to the different medical processes: diagnosis/unmasking stage, surgery/cleaning out, chemotherapy/loss of identity, radiotherapy/transition to normality, follow-up care/the "new" day-to-day, relapse/starting over, and metastatic/time-limited chronic breast cancer. The most relevant aspects of each are highlighted, as are the various cross-sectional aspects that manifest throughout the entire patient journey. CONCLUSIONS: Comprehending patients' experiences in depth facilitates the detection of situations of risk and helps to identify key moments when more precise information should be offered. Similarly, preparing the women for the process they must confront and for the sequelae of medical treatments would contribute to decreasing their uncertainty and concern, and to improving their quality-of-life.

Changing the History of Prostate Cancer with New Targeted Therapies.

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) is changing due to the emergence of new targeted therapies for the treatment of different molecular subtypes. Some biomarkers are described as potential molecular targets different from classic androgen receptors (AR). Approximately 20-25% of mCRPCs have somatic or germline alterations in DNA repair genes involved in homologous recombination. These subtypes are usually associated with more aggressive disease. Inhibitors of the enzyme poly ADP ribose polymerase (PARPi) have demonstrated an important benefit in the treatment of these subtypes of tumors. However, tumors that resistant to PARPi and wildtype BRCA tumors do not benefit from these therapies. Recent studies are exploring drug combinations with phosphatidylinositol-3-kinase (PI3K) or protein kinase B (AKT) inhibitors, as mechanisms to overcome resistance or to induce BRCAness and synthetic lethality. This article reviews various different novel strategies to improve outcomes in patients with prostate cancer.

Ascertaining breast cancer patient experiences through a journey map: A qualitative study protocol.

BACKGROUND: The current cancer care system must be improved if we are to have in-depth knowledge about breast cancer patients' experiences throughout all the stages of their disease. AIM: This study seeks to describe breast cancer patients' experience over the course of the various stages of illness by means of a journey model. METHODS: This is a qualitative descriptive study. Individual, semi-structured interviews will be administered to women with breast cancer and breast cancer survivors. Patients will be recruited from nine large hospitals in Spain and intentional sampling will be used. Data will be collected by means of a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data will be processed adopting a thematic analysis approach. DISCUSSION: The outcomes of this study will afford new insights into breast cancer patients' experiences, providing guidance to improve the care given to these individuals. This protocol aims to describe the journey of patients with breast cancer through the healthcare system to establish baseline data that will serve as the basis for the development and implementation of a patient-centered, evidence-based clinical pathway.

Final Overall Survival Analysis of the SOGUG Phase 2 MAJA Study: Maintenance Vinflunine Versus Best Supportive Care After First-Line Chemotherapy in Advanced Urothelial Carcinoma.

INTRODUCTION: The MAJA study compared vinflunine (VFL) plus best supportive care (BSC) maintenance therapy versus BSC alone in advanced urothelial carcinoma responsive to first-line chemotherapy. The primary end point of progression-free survival was achieved. We present the final overall survival (OS) and long-term follow-up safety analyses. PATIENTS AND METHODS: Patients were enrolled, and a subsequent post hoc analysis was performed on the basis of radiologic response or stabilization to first-line cisplatin/gemcitabine (CG) chemotherapy (4-6 cycles), according to Response Evaluation Criteria in Solid Tumors (RECIST). VFL + BSC versus BSC alone were randomly assigned until disease progression. RESULTS: At final analysis, 58 patients (66.7%) had died while 29 (33.3%) had survived; the BSC arm had higher mortality (VFL + BSC, n = 26, 59.1% vs. BSC, n = 32, 74.4%). Median follow-up of surviving patients was 38.8 months (interquartile range, 23.8-61.6). Median OS was 16.7 months (95% confidence interval, 0-34.5) in VFL and 13.2 months (95% confidence interval, 6-20.4) in the BSC groups (hazard ratio, 0.736; 95% confidence interval, 0.44-1.24, P = .182). Post hoc group division did not affect median OS in either study arm. CONCLUSION: Final analysis supported a benefit of VFL in maintenance therapy in patients with disease control after first-line treatment with CG, with no unexpected long-term adverse effects. The study was insufficiently powered to show a significant OS advantage.

Weekly cabazitaxel plus prednisone is effective and less toxic for 'unfit' metastatic castration-resistant prostate cancer: Phase II Spanish Oncology Genitourinary Group (SOGUG) trial.

AIM: Cabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for 'unfit' mCRPC patients after docetaxel failure. METHODS: In this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m2 to eligible 'unfit' patients; oral prednisone (5 mg) was administered twice a day. Circulating tumour cells (CTCs) were also collected. New treatment scheme was considered effective if at least 65% of patients met a clinical benefit criteria based on prostate-specific antigen (PSA)-progression-free survival (PFS) values at week 12. RESULTS: Seventy patients (median age: 73.9 years) were enrolled; overall, 71.4% had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2; and 84%, 16% and 11% had bone, liver and lung metastases, respectively. Objective partial response or stable disease was achieved in 61% of patients, while PSA responses of ≥50% and ≥80% were observed in 34.8% and 10.6%, respectively. The median PSA-PFS was 4.8 months; and 68.6% of patients had no progression at week 12. The most frequent grade 3/4 toxicities were neutropenia (2.8%), leukopenia (5.7%) and thrombocytopaenia (9%); no cases of febrile neutropenia were reported. Early CTC response was significantly correlated with PSA-PFS. CONCLUSIONS: CBZ/prednisone administered weekly to 'unfit' mCRPC patients appears to be as effective as classical standard 3-week scheme (TROPIC study) but with significantly lower toxicities and better tolerance. Early CTC response appears to be valuable as an early end-point of therapeutic efficacy.

Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial.

BACKGROUND: Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. METHODS: We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m2 or at 280 mg/m2 in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. FINDINGS: Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One patient from the vinflunine group was lost to follow-up immediately after randomisation and was excluded from the analyses. One patient in the best supportive care group became ineligible for the study and did not receive treatment due to a delay in enrolment, but was included in the intention-to-treat efficacy analysis. After a median follow-up of 15·6 months (IQR 8·5-26·0), 29 (66%) of 44 patients in the vinflunine group had disease progression and 24 (55%) had died, compared with 36 (84%) of 43 patients with disease progression and 32 (74%) deaths in the best supportive care group. Median progression-free survival was 6·5 months (95% CI 2·0-11·1) in the vinflunine group and 4·2 months (2·1-6·3) in the best supportive care group (hazard ratio 0·59, 95% CI 0·37-0·96, p=0·031). The most common grade 3 or 4 adverse events were neutropenia (eight [18%] of 44 in the vinflunine group vs none of 42 in the best supportive care group), asthenia or fatigue (seven [16%] vs one [2%]), and constipation (six [14%] vs none). 18 serious adverse events were reported in the vinflunine group and 14 in the best supportive care group. One patient in the vinflunine group died from pneumonia that was deemed to be treatment related. INTERPRETATION: In patients with disease control after first-line chemotherapy, progression-free survival exceeded the acceptable threshold with vinflunine maintenance therapy. Moreover, progression-free survival was longer with vinflunine maintenance therapy than with best supportive care. Vinflunine maintenance had an acceptable safety profile. Further studies of the role of vinflunine are warranted. FUNDING: Pierre-Fabre Médicament.

Mammographic density and breast cancer in women from high risk families.

INTRODUCTION: Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in BRCA1/2 mutation carriers and non-carriers from BRCA1/2 mutation-positive families and investigated the association between MD and BC among BRCA1/2 mutation carriers per type of mutation and tumor subtype. METHODS: The study was carried out in 1039 female members of BRCA1 and BRCA2 mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants' density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (<10 %, 10-25 %, 25-50 %, 50-75 %, >75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in BRCA1/2 mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype. RESULTS: We identified and scored mammograms from 341 BRCA1, 350 BRCA2 mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among BRCA2 mutation carriers (odds ratio (OR) =0.71; P-value=0.04), but not among BRCA1 carriers (OR=0.84; P-value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, P-value<0.001), with no significant differences between BRCA1 and BRCA2 mutation carriers (P-value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes. CONCLUSIONS: Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either BRCA1 and BRCA2 mutation carriers, and should be considered a phenotype risk marker in this context.

[CT-guided radiofrequency ablation of non-small cell lung cancer]. / Ablación por radiofrecuencia guiada por tomografía computarizada en el carcinoma de pulmón no microcítico.

UNLABELLED: FUNDAMENTAL AND OBJECTIVE: To present the first experiences with a series of consecutive cases of patients with non-small cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA), considering its clinical applicability, effectiveness and safety. PATIENTS AND METHODS: Descriptive study performed from June 2003 to March 2009, with a series of consecutive cases of patients with NSCLC treated with RFA, selected according to well-defined inclusion criteria, in different stages of the disease. The variables studied were local recurrence, complications, staging, demographic and procedure-related variables. Local control was assessed in posterior controls according to CT morphology criteria and/or lesion enhancement after intravenous contrast. Survival curves were estimated. Statistical analysis was performed with SPSS version 15.0 application. RESULTS: We studied 15 patients (46-88 years), diagnosed with NSCLC in different stages, in a total of 22 sessions. After 1 year of follow up, 75% of lesions showed no local recurrence (15). The progression-free survival and disease-free survival in localized stage at one year were 81,3% and 75% respectively. In 8 of 22 sessions there were post-procedure complications (36.36%). Of all complications (14), 28.5% were pneumothorax, 21.4% alveolar hemorrhage and 7.1% pulmonary infarction. CONCLUSION: ARF is clinically useful in the treatment of patients with inoperable NSCLC, considering the high percentage of local control and few major complications, being thus a plausible, effective and safe therapeutic alternative.