Dynamic nature of BRAF or KRAS p.G12C mutations in second-line therapy for advanced colorectal cancer patients: do early and late effects exist?

INTRODUCTION: The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course. METHODS: The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation. RESULTS: We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the deleterious effect of BRAF V600E vs other genotypes dissipating over time when subjects receive antiangiogenics, or KRAS G12V and G12C showing increasing aggressiveness over time. Thus, contrary to expectations, the 12-month survival rate from the second line for those who survived >6 months was 49.9% (95% CI, 32.7-67.3) for KRAS G12C and 59% (95% CI, 38.5-80.6) for BRAF V600E. CONCLUSIONS: The dynamic perspective is essential for understanding the behaviour of tumours with specific genotypes, especially from the second line onward. This may be relevant in patient monitoring and treatment decision-making, particularly in cases with distinct mutations.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Anxiety and depression in patients with advanced cancer during the COVID-19 pandemic.

OBJECTIVE: Cancer patients are at increased risk for psychological difficulties and COVID-19. We sought to analyze anxiety and depression levels during the COVID-19 pandemic and the association between sociodemographic, clinical, and psychological factors in patients with advanced cancer. METHODS: A prospective, multicenter cohort of 401 consecutive patients with newly diagnosed, advanced cancer completed the Brief Symptom Inventory, Michel Uncertainty in Illness Scale, Herth Hope Index, and Cancer Worry Scale between February 2020 and May 2021. Linear regression analyses explored the effects of uncertainty, hopelessness, and cancer worry on anxiety and depression, adjusting for sociodemographic and clinical variables. RESULTS: The incidence of anxiety and depression was 36% and 35%, respectively. Emotional distress was greater among women, patients < 65 years of age, and those with an estimated survival of > 18 months. Linear regression analysis revealed that being female, preoccupation about cancer, and hopelessness were associated with increased levels of anxiety (p < 0.001) and depression (p < 0.001) and younger age was associated with a higher risk of anxiety. No differences in anxiety or depression levels were found in relation to marital status, children, educational level, cancer type, histology, stage, or type of treatment. CONCLUSIONS: Patients with advanced cancer who initiated treatment during the pandemic experienced high levels of depression and anxiety. Early diagnosis and the development of intervention strategies are necessary, especially for specific patient subgroups, such as young women with long survival times.

Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer.

BACKGROUND: MicroRNAs (miRs) are frequently altered in colorectal cancer (CRC) and can be used as prognostic factors. OBJECTIVE: To confirm in stage III CRC patients a reported miR signature that was associated to the presence of metastatic disease. To correlate miR expression with microsatellite instability (MSI) and mutations in RAS and BRAF. METHODS: miR-21, miR-135a, miR-206, miR-335 and miR-Let-7a expression was analyzed by RT-qPCR in 150 patients out of the 329 patients used to analyze MSI and RAS and BRAF mutations. Association with disease free survival (DFS) and overall survival (OS) was analyzed. Data was confirmed by a multivariate analysis. RESULTS: MiR-21 high expression (p= 0.034) and miR-335 low expression (p= 0.0061) were significantly associated with MSI-H. A positive trend (p= 0.0624) between miR-135a high expression and RAS mutations was found. Lower miR-21 expression levels are associated with DFS (HR = 2.654, 95% CI: 1.066-6.605, p= 0.036) and a trend with OS (HR = 2.419, 95% CI: 0.749-7.815, p= 0.140). MiR-21 high expression significantly improves DFS of the poor prognosis group (T4 or N2) (p= 0.03). CONCLUSIONS: Association of increased expression of miR-21 and better prognosis in the poor prognostic group may be of interest and could be explored in future prospective clinical trials.

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.

Prediction of quality of life in early breast cancer upon completion of adjuvant chemotherapy.

Quality of life (QoL) is a complex, ordinal endpoint with multiple conditioning factors. A predictive model of QoL after adjuvant chemotherapy can support decision making or the communication of information about the range of treatment options available. Patients with localized breast cancer (n = 219) were prospectively recruited at 17 centers. Participants completed the EORTC QLQ-C30 questionnaire. The primary aim was to predict health status upon completion of adjuvant chemotherapy adjusted for multiple covariates. We developed a Bayesian model with six covariates (chemotherapy regimen, TNM stage, axillary lymph node dissection, perceived risk of recurrence, age, type of surgery, and baseline EORTC scores). This model allows both prediction and causal inference. The patients with mastectomy reported a discrete decline on all QoL scores. The effect of surgery depended on the interaction with age. Women with ages on either end of the range displayed worse scores, especially with mastectomy. The perceived risk of recurrence had a striking effect on health status. In conclusion, we have developed a predictive model of health status in patients with early breast cancer based on the individual's profile.

Multidimensional scale of perceived social support (mspss) in cancer patients: psychometric properties and measurement invariance / Escala Multidimensional de Apoyo Social Percibido (MSPSS) en pacientes con cáncer: propiedades psicométricas e invariancia de medida

BACKGROUND: The aim of this study was to evaluate the psychometric properties, convergent validity, and factorial invariance of the Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients. METHOD: Confirmatory factor analysis (CFA) was conducted to explore the scale's dimensionality and test for strong measurement invariance across sex and age in a cross-sectional, multicenter, prospective study. Patients completed the MSPSS and Satisfaction with Life Scale (SWLS). RESULTS: A total of 925 consecutive patients were recruited in 13 hospitals between July 2015 and December 2018. The CFA indicated that the original three-factor model was replicated in patients with cancer. The results of the multi-group CFA revealed a strong invariance according to sex and age. The Spanish version of the MSPSS had high estimated reliability with values exceeding .90. The simple sum of the items of each scale was a good indicator of oncology patients' perceived social support. The three MSPSS subscales correlated significantly with the SWLS. Women scored higher on social support by friends than men. CONCLUSION: The Spanish version of the MSPSS proved to be a valid, reliable instrument to assess perceived social support in cancer patients

ANTECEDENTES: el objetivo de este estudio fue evaluar las propiedades psicométricas, la validez convergente y la invariancia factorial de la Escala Multidimensional de Apoyo Social Percibido (MSPSS) en pacientes con cáncer. MÉTODO: el análisis factorial confirmatorio (CFA) se realizó para explorar la dimensionalidad de la escala y la invariancia de medición por sexo y edad en un estudio prospectivo, transversal y multicéntrico. Los pacientes completaron el MSPSS y la Escala de Satisfacción con la Vida (SWLS). RESULTADOS: un total de 925 pacientes consecutivos fueron reclutados en 13 hospitales entre julio de 2015 y diciembre de 2018. El CFA indicó que el modelo original de tres factores fue replicado en pacientes con cáncer. Los resultados del CFA multigrupo revelaron invariancia fuerte según el sexo y la edad. La versión en español del MSPSS tenía una alta fiabilidad estimada, con valores superiores a 0,90. La suma simple de los ítems de cada escala fue un buen indicador del apoyo social percibido de los pacientes oncológicos. Las tres subescalas MSPSS se correlacionaron significativamente con el SWLS. CONCLUSIÓN: la versión en español del MSPSS demostró ser un instrumento válido y confiable para evaluar el apoyo social percibido en pacientes con cáncer

Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients: psychometric properties and measurement invariance.

BACKGROUND: The aim of this study was to evaluate the psychometric properties, convergent validity, and factorial invariance of the Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients. METHOD: Confirmatory factor analysis (CFA) was conducted to explore the scale's dimensionality and test for strong measurement invariance across sex and age in a cross-sectional, multicenter, prospective study. Patients completed the MSPSS and Satisfaction with Life Scale (SWLS). RESULTS: A total of 925 consecutive patients were recruited in 13 hospitals between July 2015 and December 2018. The CFA indicated that the original three-factor model was replicated in patients with cancer. The results of the multi-group CFA revealed a strong invariance according to sex and age. The Spanish version of the MSPSS had high estimated reliability with values exceeding .90. The simple sum of the items of each scale was a good indicator of oncology patients' perceived social support. The three MSPSS subscales correlated significantly with the SWLS. Women scored higher on social support by friends than men. CONCLUSION: The Spanish version of the MSPSS proved to be a valid, reliable instrument to assess perceived social support in cancer patients.

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.