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Comorbid anxiety and depression predict a poorer prognosis than either disorder occurring alone. It is unclear whether self-reported anxiety symptom scores identify patients with depression in need of more intensive mental health services. This study evaluated how anxiety symptoms predicted treatment receipt and outcomes among patients with new depression diagnoses in the Veterans Health Administration (VHA). Electronic medical record data from 128,917 VHA patients (71.6% assessed for anxiety, n = 92,237) with new diagnoses of depression were analyzed to examine how Generalized Anxiety Disorder-7 (GAD-7) scores predicted psychotropic medication prescriptions, psychotherapy receipt, acute care service utilization, and follow-up depression symptoms. Patients who reported severe symptoms of anxiety were significantly more likely to receive adequate acute phase and continuation phase antidepressant treatment, daytime anxiolytics/sedatives, nighttime sedative/hypnotics, and endorse more severe depression symptoms and suicidal ideation at follow-up. Patients who reported severe symptoms of anxiety at baseline were less likely to initiate psychotherapy. The GAD-7 may help identify depressed patients who have more severe disease burden and require additional mental health services.
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INTRODUCTION: Aspects of social relationships have variably been associated with suicidal ideation (SI) and suicide attempts (SAs). This study assessed whether social support and social distress measures have general factors versus measure-specific factors that are associated with suicide risk. METHODS: Adults (N = 455, 60.0% female), admitted to psychiatric inpatient units following a recent suicide attempt or active SI, completed assessments of social support (emotional support, instrumental support, friendship, perceived support from significant others, friends, family) and social distress (loneliness, perceived rejection, perceived burdensomeness, thwarted belongingness). Bifactor modeling examined general and specific factors of social support and distress in relation to SI (week prior to hospitalization, via the Beck Scale for SI) and SAs (past 30 days, via the Columbia Suicide Severity Rating Scale). RESULTS: SI was significantly associated with the general social support (B = -1.51), the general social distress (B = 1.67), and the specific perceived burdensomeness (B = 1.57) factors. SAs were significantly associated with the specific Perceived Rejection (OR = 1.05) and Thwarted Belongingness (OR = 0.91) factors. CONCLUSION: General social support and social distress were associated with SI but not recent SAs. Specific social distress factors were also related to SI and SAs controlling for general social distress, suggesting areas for future interventions.
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OBJECTIVE: Evaluate outcomes of Veterans who discontinued treatment with at least moderate ongoing depressive symptoms. METHOD: Veterans with elevated depression symptoms from 29 Department of Veterans Affairs facilities completed baseline surveys and follow-up assessments for one year. Analyses examined rates and predictors of treatment discontinuation, treatment re-engagement, and subsequent symptoms among patients who remained out of care. RESULTS: A total of 242 (17.8%; n = 1359) participants discontinued treatment while symptomatic, with Black participants, participants with less severe depression, and participants receiving only psychotherapy (versus combined psychotherapy and antidepressant medications) discontinuing at higher rates. Among all participants who discontinued treatment (n = 445), 45.8% re-engaged within the following six months with participants receiving combined treatment re-engaging at higher rates. Of participants who discontinued while symptomatic within the first 6 months of the study and did not return to care (n = 112), 68.8% remained symptomatic at 12 months. Lower baseline treatment expectancy and greater depression symptom severity were associated with remaining symptomatic while untreated. CONCLUSIONS: Black race, lower symptom severity, and treatment modality may help identify patients at higher risk for discontinuing care while symptomatic, whereas patients with lower treatment expectations may be at greater risk for remaining out of care despite continuing symptoms.
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Trastorno Depresivo , Veteranos , Humanos , Estados Unidos/epidemiología , Depresión/terapia , Trastorno Depresivo/diagnóstico , Antidepresivos/uso terapéutico , Psicoterapia , United States Department of Veterans AffairsRESUMEN
BACKGROUND: Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has been approved by the European Medicines Agency as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic CRC in whom it is not possible to continue treatment with another FP due to hand-foot syndrome (HFS) or cardiovascular toxicity (CVT). Subsequently, this indication has been included in the 2022 ESMO guidelines for metastatic CRC. Recommendations for use in daily practice are not available. PATIENTS AND METHODS: Based on peer-reviewed published data on the use of S-1 in Western patients with metastatic CRC who switched from infusional 5-fluorouracil (5-FU) or capecitabine to S-1 for reasons of HFS or CVT, recommendations for its use were formulated by an international group of medical oncologists with expertise in the treatment of metastatic CRC and a cardio-oncologist. RESULTS: In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU. S-1 should preferably be initiated at full dose when HFS has decreased to grade ≤1. In patients with cardiac complaints, in whom an association with capecitabine or infusional 5-FU treatment cannot be excluded, capecitabine/5-FU should be discontinued and a switch to S-1 is recommended. CONCLUSIONS: These recommendations should guide clinicians in daily practice in the treatment of patients with metastatic CRC with FP-containing regimens.
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Neoplasias del Colon , Neoplasias Colorrectales , Síndrome Mano-Pie , Humanos , Capecitabina/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Síndrome Mano-Pie/etiología , Síndrome Mano-Pie/tratamiento farmacológico , Fluorouracilo/efectos adversos , Irinotecán/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Factores Inmunológicos/uso terapéuticoRESUMEN
BACKGROUND: Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m2) and doxorubicin (2.1 mg/m2) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy. RESULTS: Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy. CONCLUSIONS: Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe.
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Laparoscopía , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Cisplatino , Estudios Prospectivos , Estudios de Factibilidad , Neoplasias Peritoneales/tratamiento farmacológico , Doxorrubicina , AerosolesRESUMEN
BACKGROUND: In 2020, the European Medicines Agency recommended testing patients for dihydropyrimidine dehydrogenase (DPD) deficiency before systemic treatment with fluoropyrimidines (FP). DPD activity testing identifies patients at elevated risk of severe FP-related toxicity (FP-TOX). The two most used methods for DPD testing are DPYD genotyping and DPD phenotyping (plasma uracil concentration). The primary objective of this study was to compare the overall frequency of overall grade ≥3 FP-TOX before and after the implementation of DPYD genotyping. PATIENTS AND METHODS: Two hundred thirty Danish, primarily gastrointestinal cancer patients, were DPYD-genotyped before their first dose of FP, and blood was sampled for post hoc assessment of P-uracil. The initial dose was reduced for variant carriers. Grade ≥3 FP-TOX was registered after the first three treatment cycles of FP. The frequency of toxicity was compared to a historical cohort of 492 patients with post hoc determined DPYD genotype from a biobank. RESULTS: The frequency of overall grade ≥3 FP-TOX was 27% in the DPYD genotype-guided group compared to 24% in the historical cohort. In DPYD variant carriers, DPYD genotyping reduced the frequency of FP-related hospitalization from 19% to 0%. In the control group, 4.8% of DPYD variant carriers died due to FP-TOX compared to 0% in the group receiving DPYD genotype-guided dosing of FP. In the intervention group, wild-type patients with uracil ≥16 ng/ml had a higher frequency of FP-TOX than wild-type patients with uracil <16 ng/ml (55% versus 28%). CONCLUSIONS: We found no population-level benefit of DPYD genotyping when comparing the risk of grade ≥3 FP-TOX before and after clinical implementation. We observed no deaths or FP-related hospitalizations in patients whose FP treatment was guided by a variant DPYD genotype. The use of DPD phenotyping may add valuable information in DPYD wild-type patients.
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Deficiencia de Dihidropirimidina Deshidrogenasa , Neoplasias Gastrointestinales , Humanos , Antimetabolitos Antineoplásicos/efectos adversos , Capecitabina/efectos adversos , Dinamarca , Deficiencia de Dihidropirimidina Deshidrogenasa/inducido químicamente , Deficiencia de Dihidropirimidina Deshidrogenasa/tratamiento farmacológico , Deficiencia de Dihidropirimidina Deshidrogenasa/genética , Dihidrouracilo Deshidrogenasa (NADP)/genética , Neoplasias Gastrointestinales/tratamiento farmacológico , Genotipo , Uracilo/uso terapéuticoRESUMEN
BACKGROUND: Pressurized Intraperitoneal Aerosol chemotherapy (PIPAC) is a local treatment for peritoneal metastasis (PM). Prospective data are scarce and evaluation of treatment response remains difficult. This study evaluated the use of the Peritoneal Regression Grading score (PRGS) and its prognostic value. PATIENTS AND METHODS: This was a prospective, controlled phase II trial in patients with PM from gastrointestinal, gynaecological, hepatopancreatobiliary, primary peritoneal, or unknown primary cancer. Patients in performance status 0-1, with a non-obstructed gastrointestinal tract, and a maximum of one extraperitoneal metastasis were eligible. Colorectal or appendiceal PM had PIPAC with oxaliplatin, other primaries had PIPAC with cisplatin and doxorubicin. Biopsies were taken at each PIPAC and evaluated using the PRGS. Quality-of-life questionnaires were reported at baseline and after three PIPACs. RESULTS: One hundred ten patients were treated with 336 PIPACs (median 3, range 1-12). One hundred patients had prior palliative chemotherapy and 45 patients received bidirectional treatment. Complete or major histological response to treatment (PRGS 1-2) was observed in 38 patients (61%) who had three PIPACs, which was the only independent prognostic factor in a multivariate analysis. The median overall survival (mOS) from PIPAC 1 was 10 months, while patients with PM from gastric, colorectal, and pancreatic cancer had a mOS of 7.4, 16.7, and 8.2 months, respectively. Global health scores were significantly reduced, but patients were less fatigued, nauseated, constipated, and had better appetite after three PIPACs. CONCLUSIONS: PIPAC with oxaliplatin or cisplatin and doxorubicin was able to induce a major or complete histological response during three PIPACs, which may provide significant prognostic information, both at baseline and after treatment.
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Neoplasias Colorrectales , Neoplasias Peritoneales , Humanos , Aerosoles , Cisplatino , Neoplasias Colorrectales/tratamiento farmacológico , Doxorrubicina , Oxaliplatino , Neoplasias Peritoneales/secundario , Estudios ProspectivosRESUMEN
BACKGROUND: 5-fluorouracil (5-FU) combined with a folate remains an essential treatment component for metastatic colorectal cancer (mCRC). Leucovorin is the folate most often used, but requires intracellular conversion to a reduced folate, and has high pharmacokinetic variability and limited bioavailability in patients with low folate pathway gene expression. Arfolitixorin is an immediately active form of folate, [6R]-5,10-methylenetetrahydrofolate ([6R]-MTHF), and may improve outcomes. PATIENTS AND METHODS: This open-label, multicenter, phase I/II study in patients with mCRC (NCT02244632) assessed the tolerability and efficacy of first- or second-line arfolitixorin (30, 60, 120, or 240 mg/m2 intravenous) with 5-FU alone, or in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan, every 14 days. Safety, efficacy, and pharmacokinetics were assessed before and after four cycles (8 weeks) of treatment. RESULTS: In 105 treated patients, investigators reported 583 adverse events (AEs) in 86 patients (81.9%), and 256 AEs (43.9%) were potentially related to arfolitixorin and 5-FU. Dose adjustments were required in 16 patients (15.2%). At 8 weeks, 9 out of 57 patients assessed for efficacy achieved an objective response (15.8%), and all 9 achieved a partial response. Six of these nine patients had received arfolitixorin as a first-line treatment. A further 33 patients (57.9%) achieved stable disease. Pharmacokinetics were assessed in 35 patients. The average tmax was 10 min, and area under the plasma concentration-time curve from time 0 to 1 h increased linearly between 30 and 240 mg/m2. No accumulation was observed for [6R]-MTHF following repeated administration, and there were no major pharmacokinetic differences between cycle 1 and cycle 4 at any dose. CONCLUSIONS: Arfolitixorin is a well-tolerated moderator of 5-FU activity. It is suitable for further investigation in mCRC and has the potential to improve treatment outcomes in patients with low folate pathway gene expression. Arfolitixorin can easily be incorporated into current standard of care, requiring minimal changes to chemotherapy regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/uso terapéutico , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Oxaliplatino/uso terapéuticoRESUMEN
BACKGROUND: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. PATIENTS AND METHODS: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. RESULTS: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). CONCLUSION: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
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Fluorouracilo , Neoplasias , Adulto , Anciano , Anciano de 80 o más Años , Capecitabina/efectos adversos , Cardiotoxicidad/etiología , Femenino , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. METHODS: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1-5 and 8-12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1-14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. RESULTS: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0-23.7) with TT-B and 17.7 months (95% CI: 12.6-19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55-1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. CONCLUSIONS: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. CLINICAL TRIAL INFORMATION: NCT02743221 (clinicaltrials.gov).
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab , Capecitabina/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Humanos , Pirrolidinas , Neoplasias del Recto/tratamiento farmacológico , Análisis de Supervivencia , Timina , Trifluridina/efectos adversosAsunto(s)
Dolor Abdominal/etiología , Aerosoles/efectos adversos , Nebulizadores y Vaporizadores , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Neoplasias Peritoneales/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/secundario , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Ensayos Clínicos Fase II como Asunto , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Humanos , Neoplasias Peritoneales/secundarioRESUMEN
BACKGROUND: We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. PATIENTS AND METHODS: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. RESULTS: Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents. CONCLUSION: TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Capecitabina , Neoplasias Colorrectales , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Capecitabina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Humanos , Pirrolidinas , Calidad de Vida , Timina , Trifluridina/efectos adversosRESUMEN
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents a novel approach to deliver intraperitoneal chemotherapy. We report our experience with PIPAC in patients with peritoneal metastasis (PM) from gastric cancer (GC). Data from GC patients (n = 20) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 studies are reported. All patients had received prior systemic chemotherapy. The mean peritoneal cancer index (PCI) was 10.5 (range 0-39) and nine patients had diffuse GC. PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were administered at 4-6-week intervals. Outcome criteria were objective tumour response, survival and adverse events. Twenty patients had 52 PIPAC procedures with a median follow-up of 10.4 months (3.3-26.5). Median survival from the time of PM diagnosis and after the first PIPAC procedure was 11.5 months and 4.7 months, respectively. Fourteen patients had repeated PIPAC (> 2), and the objective tumour response according to the histological peritoneal regression grading score (PRGS) was observed in 36%, whereas 36% had stable disease. Ten patients completed the three prescheduled sessions (per protocol group) and 40% of those displayed an objective tumour response, while 20% had stable disease. Only minor postoperative complications were noted, and none were considered causally related to the PIPAC treatment. PIPAC with low-dose cisplatin and doxorubicin can induce a quantifiable objective tumour response in selected patients with PM from GC. Survival data are encouraging and warrant further clinical studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Peritoneo/patología , Neoplasias Gástricas/tratamiento farmacológico , Administración Tópica , Adulto , Aerosoles , Anciano , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Peritoneo/efectos de los fármacos , Presión , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. METHODS: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. RESULTS: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. CONCLUSIONS: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.
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Antineoplásicos/efectos adversos , Conducción Nerviosa/fisiología , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Polineuropatías/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Fibras Nerviosas/patología , Examen Neurológico , Oxaliplatino/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/patología , Polineuropatías/inducido químicamente , Polineuropatías/patología , Piel/patología , Nervio Sural/patología , Nervio Sural/fisiopatologíaRESUMEN
BACKGROUND: Upper gastrointestinal malignancies have a poor prognosis. There is no consensus on how patients should be followed after surgery. The authors hypothesized that a structured follow-up programme including endoscopic ultrasonography (EUS) and [18 F]fluorodeoxyglucose (FDG) PET/CT would detect cancer recurrences, leading to more patients being eligible for therapy. METHODS: After surgery with curative intent for adenocarcinomas in the gastro-oesophageal junction, stomach or pancreas, patients were randomized 1 : 1 to standard clinical assessment in the outpatient clinic at 3, 6, 9, 12, 18 and 24 months after operation, or clinical assessment plus imaging including [18 F]FDG PET/CT and EUS. The primary endpoint was number of patients receiving oncological treatment for recurrence. Secondary endpoints were overall and progression-free survival, survival after recurrence detection of isolated locoregional recurrences and risk factors affecting survival. RESULTS: In total, 183 patients were enrolled, including 93 who underwent standard follow-up and 90 who had follow-up plus imaging. A recurrence was detected in 84 patients within 2 years after surgery (42 in each group), including 33 of 42 patients in the imaging group who were asymptomatic. Some 25 of 42 patients in the imaging group and 14 of 42 in the standard group received chemotherapy (P = 0·028). Although survival after detection of recurrence in asymptomatic patients was significantly longer than that for symptomatic patients (P < 0·001), overall survival from date of surgery in the two treatment groups was comparable. CONCLUSION: Follow-up after surgery for upper gastrointestinal cancer with EUS and PET/CT leads to detection of more asymptomatic cancer recurrences and patients referred for treatment without prolonging overall survival. Registration number: NCT02209415 ( http://www.clinicaltrials.gov).
ANTECEDENTES: Las neoplasias del tracto digestivo superior tienen un mal pronóstico. No existe consenso sobre en qué pacientes debe indicarse un seguimiento tras la cirugía. Se estableció la hipótesis de que un programa de seguimiento estructurado en el que se incluía ecoendoscopia (endosonography, EUS) y 18F-FDG-PET/CT detecta recidivas del cáncer logrando que más pacientes sean elegibles para tratamiento. MÉTODOS: Después de cirugía con intención curativa para adenocarcinomas de la unión gastroesofágica, estómago o páncreas, los pacientes fueron aleatorizados 1:1 a evaluación clínica estándar en consultas externas a los 3, 6, 9, 12, 18, y 24 meses postoperatorios o evaluación clínica más pruebas de diagnóstico por la imagen en las que se incluían 18F-FDG-PET/CT y EUS. La variable principal fue el número de pacientes que recibieron tratamiento oncológico para la recidiva. Las variables secundarias fueron la supervivencia global y libre de progresión, supervivencia tras la recidiva, la detección de recidivas locorregionales aisladas (isolated loco-regional recurrences, ILR) y factores de riesgo que afectan a la supervivencia. RESULTADOS: En total se reclutaron 183 pacientes, incluyendo 93 pacientes sometidos a un seguimiento estándar (controles) y 90 pacientes con seguimiento y pruebas de imagen. Se detectó recidiva en 84 pacientes dentro de los primeros dos años tras la cirugía (42 pacientes en cada grupo), incluyendo 33 de 42 pacientes (78%) en el grupo con pruebas de imagen que estaban asintomáticos. Veinticinco de 42 pacientes (60%) del grupo con pruebas de imagen y 14 de 42 pacientes (33%) del grupo control recibieron quimioterapia (P = 0,03). Aunque la supervivencia tras la detección de la recidiva en pacientes asintomáticos fue significativamente más larga en comparación con los pacientes sintomáticos (P < 0,001), la supervivencia global desde la fecha de la cirugía en las dos ramas del tratamiento fue comparable. CONCLUSIÓN: El seguimiento tras la cirugía del cáncer gastrointestinal del tracto superior con EUS y PET-CT permite detectar más recidivas asintomáticas de la enfermedad y derivar a los pacientes para tratamiento sin que ello prolongue la supervivencia global.
Asunto(s)
Adenocarcinoma/diagnóstico , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Endosonografía/métodos , Neoplasias Gastrointestinales/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Cuidados Posoperatorios/métodos , Adenocarcinoma/cirugía , Anciano , Dinamarca/epidemiología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
Perovskite solar cells have shown a rapid increase of performance and overcome the threshold of 20% power conversion efficiency (PCE). The main issues hampering commercialization are the lack of deposition methods for large areas, missing long-term device stability and the toxicity of the commonly used Pb-based compounds. In this work, we present a novel chemical vapor deposition (CVD) process for Pb-free air-stable methylammonium bismuth iodide (MBI) layers, which enables large-area production employing close-coupled showerhead technology. We demonstrate the influence of precursor rates on the layer morphology as well as on the optical and crystallographic properties. The impact of substrate temperature and layer thickness on the morphology of MBI crystallites is discussed. We obtain smooth layers with lateral crystallite sizes up to 500 nm. Moreover, the application of CVD-processed MBI layers in non-inverted perovskite solar cells is presented.