Predicting Chemotherapy Toxicity in Older Patients with Cancer: A Multicenter Prospective Study.

BACKGROUND: Standard oncology tools are inadequate to distinguish which older patients are at higher risk of developing chemotherapy-related complications. MATERIALS AND METHODS: Patients over 70 years of age starting new chemotherapy regimens were prospectively included in a multicenter study. A prechemotherapy assessment that included sociodemographics, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and the development of grade 3-5 toxicity was examined by using logistic regression. RESULTS: A total of 551 patients were accrued. Chemotherapy doses (odds ratio [OR] 1.834; 95% confidence interval [CI] 1.237-2.719) and creatinine clearance (OR 0.989; 95% CI 0.981-0.997) were the only factors independently associated with toxicity. Only 19% of patients who received reduced doses of chemotherapy and had a creatinine clearance ≥40 mL/minute had grade 3-4 toxicity, compared with 38% of those who received standard doses or had a creatinine clearance <40 mL/minute (p < .0001). However, no satisfactory multivariate model was obtained using different selection approaches. CONCLUSION: Chemotherapy doses and renal function were identified as the major risk factors for developing severe toxicity in the older patient. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up in these patients. IMPLICATIONS FOR PRACTICE: Older patients are more vulnerable to chemotherapy toxicity. However, standard tools are inadequate to identify who is at higher risk of developing chemotherapy-related complications. Chemotherapy doses (standard vs. reduced) and renal function were identified as the major risk factors for developing severe toxicity in the elderly. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up.

Longitudinal study of cognitive dysfunctions induced by adjuvant chemotherapy in colon cancer patients.

BACKGROUND: Chemotherapy can induce cognitive impairment in cancer patients. The main goal of this longitudinal study was to determine the incidence, characteristics, and duration of cognitive dysfunction in patients treated with adjuvant chemotherapy for colon cancer. PATIENTS AND METHODS: We assessed cognitive function, quality of life, anxiety and depression, fatigue, and hemoglobin levels in colon cancer patients at three assessment points: pre-chemotherapy (n=81), post-chemotherapy (n=73), and after 6-month follow-up (n=54). All patients were treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) for 6 months. RESULTS: Thirty patients (37%) had cognitive impairment in the pre-chemotherapy evaluation, mainly in processing speed and psychomotor executive function (Trail Making Test A and B). At the end of treatment, the main domain affected was the verbal memory, with an acute decline detected in 56% of patients. Fifty-four percent of the patients improved their dysfunction after 6 months of follow-up, whereas 18 (33%) of them showed worsening in at least one test. Cognitive impairment was most common in older patients and in those with less years of education. Quality of life, anxiety, depression, fatigue, and hemoglobin did not influence the results of the cognitive tests. CONCLUSIONS: Adjuvant FOLFOX4 in patients with colon cancer can have a negative effect on verbal memory. This deterioration is usually mild and transient.

SEOM-GEMCAD-TTD clinical guideline for the diagnosis and treatment of gastric cancer (2023).

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, the incidence is lower and GC represents the tenth most frequent tumor and the seventh cause of cancer mortality. Molecular biology knowledge allowed to better profile patients for a personalized therapeutic approach. In the localized setting, the multidisciplinary team discussion is fundamental for planning the therapeutic approach. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors, and chemoradiation + surgery + adjuvant immunotherapy for the GEJ are current standards. For the metastatic setting, biomarker profiling including Her2, PD-L1, MSS status is needed. Chemotherapy in combination with checkpoint inhibitors had improved the outcomes for patients with PD-L1 expression. Her2 positive patients should receive antiHer2 therapy added to chemotherapy. We describe the different evidences and recommendations based on the literature.

Predicting Risk of Severe Toxicity and Early Death in Older Adult Patients Treated with Chemotherapy.

BACKGROUND: Determining the risk of grade 3-5 toxicity and early death (ED) is important to plan chemotherapy in older adult patients with cancer. Our objective was to identify factors predicting these complications at the time of treatment initiation. METHODS: 234 patients aged ≥70 were subjected to a geriatric assessment and variables related to the tumor and the treatment were also collected. Logistic regression multivariable analysis was used to relate these factors with the appearance of grade 3-5 toxicity and ED. Predictive scores for both toxicity and ED were then developed. RESULTS: Factors related to grade 3-5 toxicity were hemoglobin, MAX2 index, ADL, and the CONUT score. Factors related to ED were tumor stage and the GNRI score. Two predictive scores were developed using these variables. ROC curves for the prediction of toxicity and ED were 0.71 (95% CI: 0.64-0.78) and 0.73 (95% CI: 0.68-0.79), respectively. CONCLUSIONS: Two simple and reliable scores were developed to predict grade 3-5 toxicity and ED in older adult patients with cancer. This may be helpful in treatment planning.

Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience.

BACKGROUND: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. METHODS: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. RESULTS: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). CONCLUSIONS: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.

SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021).

Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

Clinical Score to Predict Recurrence in Patients with Stage II and Stage III Colon Cancer.

Background: The prognosis of patients with stage II and stage III colon cancer is heterogeneous. Clinical and pathological characteristics, such as tumor budding, may help to further refine the recurrence risk. Methods: We included all the patients with localized colon cancer at Hospital Universitario La Paz from October 2016 to October 2021. We built a prognostic score for recurrence in the training cohort based on multivariate cox regression analysis and categorized the patients into two risk groups. Results: A total of 440 patients were included in the training cohort. After a median follow-up of 45 months, 81 (18%) patients had a first tumor recurrence. T4, N2, and high tumor budding remained with a p value <0.05 at the last step of the multivariate cox regression model for time to recurrence (TTR). We assigned 2 points to T4 and 1 point to N2 and high tumor budding. Forty-five percent of the patients were assigned to the low-risk group (score = 0). Compared to the high-risk group (score 1−4), patients in the low-risk group had a significantly longer TTR (hazard ratio for disease recurrence of 0.14 (95%CI: 0.00 to 0.90; p < 0.045)). The results were confirmed in the validation cohort. Conclusions: In our study, we built a simple score to predict tumor recurrence based on T4, N2, and high tumor budding. Patients in the low-risk group, that comprised 44% of the cohort, had an excellent prognosis.

Prediction of Unplanned Hospitalizations in Older Patients Treated with Chemotherapy.

PURPOSE: To determine the incidence of unplanned hospitalization (UH) and to identify risk factors for UH in elderly patients with cancer who start chemotherapy. METHODS: In all, 493 patients over 70 years starting new chemotherapy regimens were prospectively included. A pre-chemotherapy geriatric assessment was performed, and tumor and treatment variables were collected. The association between these factors and UH was examined by using multivariable logistic regression. Score points were assigned to each risk factor. RESULTS: During the first 6 months of treatment, 37% of patients had at least one episode of UH. Risk factors were the use of combination chemotherapy at standard doses, a MAX2 index ≥1, a Charlson comorbidity score ≥2, albumin level <3.5 g/dL, falls in the past 6 months ≥1, and weight loss >5%. Three risk groups for UH were established according to the score in all patients: 0-1: 17.5%; 2: 34%; and 3-7: 57% (p < 0.001). The area under receiver operation characteristic (ROC) curve was 0.72 (95% CI: 0.67-0.77). CONCLUSION: This simple tool can help to reduce the incidence of UH in elderly patients with cancer who are scheduled to initiate chemotherapy treatment.

Prediction of Chemotoxicity, Unplanned Hospitalizations and Early Death in Older Patients with Colorectal Cancer Treated with Chemotherapy.

PURPOSE: To identify risk factors for toxicity, unplanned hospitalization (UH) and early death (ED) in older patients with colorectal carcinoma (CRC) initiating chemotherapy. METHODS: 215 patients over 70 years were prospectively included. Geriatric assessment was performed before treatment, and tumor and treatment variables were collected. The association between these factors and grade 3-5 toxicity, UH and ED (<6 months) was examined by using multivariable logistic regression. Score points were assigned to each risk factor. RESULTS: During the first 6 months of treatment, 33% of patients developed grade 3-5 toxicity, 31% had UH and 23% died. Risk factors were, for toxicity, instrumental activities of daily living, creatinine clearance, weight loss and MAX2 index; for UH, Charlson Comorbidity Score, creatinine clearance, weight loss, serum albumin, and metastatic disease; and for ED, basic activities in daily living, weight loss, metastatic disease, and hemoglobin levels. Predictive scores were built with these variables. The areas under receiver operation characteristic (ROC) curves for toxicity, UH and ED were 0.70 (95% CI: 0.64-0.766), 0.726 (95% IC: 0.661-0.799) and 0.74 (95% IC: 0.678-0.809), respectively. CONCLUSION: Simple scores based on geriatric, tumor and laboratory characteristics predict severe toxicity, UH and ED, and may help in treatment planning.

Undertreatment and overtreatment in older patients treated with chemotherapy.

BACKGROUND: Inconsistent doses and schemes are commonly used in older patients receiving cancer chemotherapy. We performed this study in patients with cancer and age ≥ 70 years to determine the frequency of undertreatment and overtreatment as well as factors influencing the decision to modify chemotherapy doses. PATIENTS AND METHODS: Patients aged ≥70 years starting new chemotherapy regimens were prospectively included in a multicentre study. The schedule and drug doses were determined by the treating oncologist. Pre-chemotherapy assessment included sociodemographics, treatment details and geriatric assessment (GA) variables. Association between these factors and undertreatment (use of less intensive cancer treatment [LICT] in a fit patient) or overtreatment (use of standard cancer treatment in an unfit older patient) were examined by multivariate logistic regression. RESULTS: Three- hundred ninety-seven patients were included, 43% of whom received LICT. If not adjusted for GA, toxicity did not differ between those receiving LICT (38%) or standard doses of chemotherapy (37%). If the dose of chemotherapy was analyzed according to the results of GA 61 (15%) patients had been undertreated and 133 (34%) had been overtreated. Undertreatment was related with increasing age and decreased renal function. Factors related with overtreatment were younger age, curative intention of treatment, prescription of G-CSF as primary prophylaxis and adequate cognitive status. Overtreated patients had more grade 3-4 toxicity than those receiving treatment adapted to fragility (42% vs 31%; p < 0.05). CONCLUSIONS: The use of chemotherapy without considering GA leads to overtreatment more commonly than undertreatment in older patients with cancer. Oncologists should take into account the results of GA to stratify patients and to avoid under or overtreatment.

Development and Validation of an Early Mortality Risk Score for Older Patients Treated with Chemotherapy for Cancer.

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 years starting new chemotherapy regimens were prospectively included. A prechemotherapy assessment that included sociodemographic variables, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and early death was examined using multivariable logistic regression. Score points were assigned to each risk factor. External validation was performed on an independent cohort. Results: In the training cohort, the independent predictors of 6-month mortality were metastatic stage (OR 4.8, 95% CI [2.4-9.6]), ECOG-PS 2 (OR 2.3, 95% CI [1.1-5.2]), ADL ≤ 5 (OR 1.7, 95% CI [1.1-3.5]), serum albumin levels ≤ 3.5 g/dL (OR 3.4, 95% CI [1.7-6.6]), BMI < 23 kg/m2 (OR 2.5, 95% CI [1.3-4.9]), and hemoglobin levels < 11 g/dL (OR 2.4, 95% CI (1.2-4.7)). With these results, we built a prognostic score. The area under the ROC curve was 0.78 (95% CI, 0.73 to 0.84), and in the validation set, it was 0.73 (95% CI: 0.67-0.79). Conclusions: This simple and highly accurate tool can help physicians making decisions in elderly patients with cancer who are planned to initiate chemotherapy treatment.

SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021)

Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

Prognostic and predictive markers of benefit from adjuvant chemotherapy in early-stage non-small cell lung cancer.

Lung cancer-predominantly non-small cell lung cancer (NSCLC)-is the leading cause of death from cancer in most industrialized countries. Patients with early-stage NSCLC are at substantial risk for recurrence and death even after potentially curative surgery. Multiple large randomized trials have demonstrated that adjuvant chemotherapy using modern cisplatin-based regimens can significantly improve 5-year survival in carefully selected patients with NSCLC.The current staging system is inadequate for predicting the outcome of treatment and the prognosis in an individual patient. Molecular markers may provide additional information about the likelihood of relapse beyond that obtained from pathologic staging. They may also have value in determining which patients will benefit from adjuvant platinum-based chemotherapy.This is a review focused on approaches and specific markers under study, including gene expression profiles, DNA repair pathways, class III beta-tubulin expression, abnormalities in the k-ras oncogene and p53 tumor suppressor gene, and DNA methylation markers. Additional studies will be required to determine whether these markers are useful in selecting patients for adjuvant platinum-based chemotherapy.

Variables asociadas al deterioro cognitivo en pacientes de cáncer de colon / No disponible

Objetivo: Identificar las variables predictoras de menor rendimiento cognitivo en pacientes de cáncer de colon tratados con cirugía que esperan recibir quimioterapia. Método: En una muestra de 89 pacientes de cáncer de colon se valoró la relación entre su rendimiento en tres dominios cognitivos (función ejecutiva, memoria verbal y habilidad psicomotora) y las siguientes variables: edad, sexo, años de escolaridad, estadio, pronóstico médico, comorbilidad, hemoglobina, ansiedad, depresión, astenia, calidad de vida, problemas físicos y psicosociales. Resultados: En la muestra predominan los varones (61,8%), mayores de 65 años (media 66,9), sin antecedentes neuropsicológicos (89,9%). Los datos correlacionales ponen de manifiesto relaciones selectivas entre alguna prueba de rendimiento cognitivo y ciertas variables evaluadas. Se destaca la existencia de correlaciones negativas de la edad, los problemas respiratorios y la percepción social de la calidad de vida con el rendimiento cognitivo en pruebas de memoria verbal, función ejecutiva y habilidad psicomotora (p < 0,05). Así mismo, los pacientes en estadio III del cáncer de colon rinden peor que aquellos con la enfermedad en estadio II y quienes tienen menos de cinco años de estudios difieren de los de más estudios en los tres dominios cognitivos (p < 0,05) Conclusiones: el perfil detectado de los enfermos de cáncer de colon de alto riesgo de déficit cognitivo es: paciente mayor, con enfermedad en estadio III, de escasa formación escolar, que tiene problemas respiratorios y una buena percepción de su calidad de vida social (AU)

Objective: Identify predictors of lower cognitive performance in colon cancer patients treated with surgery before undergoing chemotherapy. Methods: In a sample of 89 colon cancer patients, we evaluated the relation between their cognitive performance in three cognitive domains (executive function, verbal memory and psychomotor skill) and the following variables: Age, sex, years of study, stage, medical prognosis, comorbidity, haemoglobin, anxiety, depression, fatigue, quality of life, physical and psychosocial problems. Results: They are a predominantly male sample (61.8%), over 65 years (mean 66.9) without neuropsychological illness history (89.9%). But, data show correlational relationships between some cognitive performance test and certain variables assessed. There are remarkable negative correlations with age, respiratory problems and social perception of the quality of life, with lower cognitive performance on tests of verbal memory, executive function and psychomotor ability (p <0.05). Also, patients with stage III colon cancer performed worse than those with stage II disease and those with less than five years of study differ from most studies in the three cognitive domains (p < 0.05). Conclusions: The profile of patients with colon cancer at high risk of cognitive deficit is: Old age, with stage III disease, little formal education, breathing problems and a good perception of their quality of social life (AU)

Bases biológicas del deterioro de la función cognitiva inducido por los tratamientos antineoplásicos / No disponible

A menudo los pacientes que reciben tratamiento con quimioterapia y/o radioterapia presentan problemas de memoria y de atención. Se desconocen los mecanismos exactos por los que esto se produce, aunque se han propuesto diversas explicaciones. Tanto la quimioterapia como la radioterapia poseen una acción tóxica directa en el SNC, especialmente sobre las células progenitoras neurales y las de la glía, que son las responsables de mantener la neurogénesis del hipocampo y la integridad de la sustancia blanca. A ello cabe añadir el daño que pueden inducir los tratamientos en la vascularización cerebral, la alteración de la respuesta inmune mediada por citoquinas, y los cambios hormonales ya sean secundarios a la quimioterapia o a la propia hormonoterapia. La intensidad de estos efectos estaría modulada por diversos factores genéticos que influyen sobre la capacidad de reparación neuronal, la farmacodinamia y la actividad de los neurotransmisores (AU)

Often patients treated with chemotherapy and/or radiotherapy suffer memory and attention problems. The exact mechanisms of action are unknown, although several explanations have been proposed. Both chemotherapy and radiotherapy have a direct toxic effect in the CNS, especially neural progenitor cells and the glia, which are responsible for maintaining neurogenesis in the hippocampus and white matter integrity. Besides the treatments can induce vascular damage in the brain, altering the immune response mediated by cytokines, and hormonal changes secondary to either chemotherapy or hormone therapy itself. The intensity of these effects would be modulated by several genetic factors that influence the ability of neuronal repair, pharmacodynamics and activity of neurotransmitters (AU)