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INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin-based chemoradiotherapy (CRT) frequently experience irreversible sensorineural hearing loss (SNHL). Patients with low lumbar skeletal muscle index (LSMI) may experience higher serum peak dosages of cisplatin. This study investigated whether pre-treatment low LSMI is associated with increased SNHL upon cisplatin-based CRT. MATERIALS AND METHODS: LSMI was assessed using routine pre-treatment CT scans. Pure tone audiometry was performed at baseline and at follow-up to assess treatment-related SNHL. Linear mixed models were used to reveal a potential association between the continuous variable LSMI and SNHL. RESULTS: This retrospective cohort study included 81 patients and found a significant association between low LSMI and increased treatment-related SNHL at pure tone frequencies vital for the perception of speech (averaged of 1, 2, and 4 kHz) (p = 0.048). CONCLUSIONS: HNSCC patients with low LSMI suffer increased treatment-related SNHL upon cisplatin-based CRT.
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BACKGROUND: The aim of the study was to compare the short-term outcome of SuperPATH, direct anterior (DAA) and conventional approach (CA) hemiarthroplasty (HA) in patients with femoral neck fractures using a network meta-analysis. METHODS: PubMed, China National Knowledge Infrastructure, Epistemonikos, and Embase were searched until May 31, 2024. In a network meta-analysis, mean differences with 95% confidence intervals were calculated using the Hartung-Knapp-Sidik-Jonkman method and a fixed/random effects model for continuous outcomes, and odds ratios with 95% confidence intervals were calculated using the Mantel-Haenszel method and a fixed/random effects model for dichotomous outcomes. RESULTS: The literature search identified a total of 9 randomized controlled trials on SuperPATH with 762 patients and 8 randomized controlled trials on DAA with 641 patients. In the overall ranking, SuperPATH was placed first, DAA second and CA third. SuperPATH HA was best in 7, second best in 2 and third best in 1 of the 10 outcome parameters. DAA HA was best in 2 and second best in 8 of the 10 outcome parameters. CA HA was best in 1 and third best in 9 of the 10 outcome parameters. In the indirect comparison between SuperPATH HA and DAA HA, SuperPATH HA had a 1.36 point lower visual analog scale at 2 to 7 days postoperatively and a 0.17 lower overall complication rate compared to DAA. CONCLUSION: For the treatment of patients with femoral neck fractures, SuperPATH HA ranked first, DAA HA ranked second and CA HA ranked third. Based on the results, we recommend that trauma surgeons increase their use of minimally invasive hip HA techniques. It should be noted that SuperPATH HA had a significantly lower overall complication rate compared to DAA HA when the minimally invasive technique was chosen.
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Fracturas del Cuello Femoral , Hemiartroplastia , Metaanálisis en Red , Fracturas del Cuello Femoral/cirugía , Humanos , Hemiartroplastia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiologíaAsunto(s)
Infecciones Estreptocócicas , Streptococcus pyogenes , Humanos , Streptococcus pyogenes/aislamiento & purificación , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/epidemiología , Incidencia , Preescolar , Masculino , Niño , Femenino , Lactante , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/microbiología , Estudios Retrospectivos , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. METHODS: We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients' outcomes were compared using Cox regression and competing risk models. RESULTS: Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18-3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78-0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9-100%). Conversely, among the 61 patients with gBRCA1m and < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7-65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29-7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19-0.95) incidence of second primary tumors, compared to BRCA1-non-alteration. CONCLUSIONS: Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.
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Neoplasias Primarias Secundarias , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Adulto , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Adyuvantes Inmunológicos , Etnicidad , Biomarcadores , Proteína BRCA1/genéticaRESUMEN
PURPOSE: Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study. METHODS: Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area. RESULTS: Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected). CONCLUSION: We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.
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Supervivientes de Cáncer , Neoplasias Colorrectales , Neoplasias Primarias Secundarias , Humanos , Niño , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios de Casos y Controles , Neoplasias Primarias Secundarias/epidemiología , Sobrevivientes , Incidencia , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: The aim of this study is to evaluate how cumulative burden of clinically relevant, self-reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications. METHODS: The authors invited 5925 5-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self-reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30-year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30-year MCC, and compared the ranking to levels of care according to existing risk stratifications. RESULTS: At median 18.5 years after 5-year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30-year MCC = 0.79; 95% confidence interval [CI], 0.74-0.85 vs. 30-year MCC = 0.29; 95% CI, 0.25-0.34). CCSs' burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30-year MCC often did not correspond with levels of care in existing risk stratifications. CONCLUSIONS: CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs' current morbidity.
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Supervivientes de Cáncer , Neoplasias , Niño , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/patología , Autoinforme , Supervivencia , SobrevivientesRESUMEN
The aim was to conduct a systematic review of literature and meta-analysis of randomized controlled trials (RCTs) comparing short-term outcomes of bipolar hemiarthroplasty (HA) through SuperPATH and bipolar HA through conventional approaches (CAs) in patients with femoral neck fractures. The following PICO question was formulated: In human participants with femoral neck fractures, are the short-term outcomes of SuperPATH HA better than the short-term outcomes of CAs HA? The following databases were searched until 25 August 2023: PubMed, CNKI, CENTRAL of The Cochrane Library, Clinical trials, and Google Scholar. Quality assessment of the RCTs was performed, according to the Cochrane's Risk of Bias 2 tool and the recommendations of the GRADE system. Furthermore, we evaluated publication bias with funnel plots. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous variables using the Hartung-Knapp-Sidik-Jonkman method and a random effects model. Nine RCTs with overall 762 patients were included in this meta-analysis. All 9 RCTs were rated with a moderate risk of bias. The quality of evidence of the outcome parameters was rated moderate to very low. The funnel plots were overall broadly symmetrical, possibly indicating low to moderate publication bias. SuperPATH had a longer operation time compared to CAs (MD = 21.79, 95% CI 12.57 to 31.02). SuperPATH decreased incision length (MD = - 4.50; 95% CI - 5.80 to - 3.20), intraoperative blood loss (MD = - 103.96, 95% CI - 150.27 to - 55.66), postoperative drainage volume (MD = - 137.30, 95% CI - 178.74 to - 95.86), time to mobilization (MD = - 3.86; 95% CI - 5.96 to - 1.76), pain VAS ≤ 1 week postoperatively (MD = - 1.81; 95% CI - 2.17 to - 1.45), and hospitalization time (MD = - 4.05; 95% CI - 4.96 to - 3.15). SuperPATH improved HHS ≤ 1 week postoperatively (MD = 11.10; 95% CI 1.65 to 20.54) and HHS 3 months postoperatively (MD = 6.33; 95% CI 3.97 to 8.69). There was no difference in pain VAS 1-3 months postoperatively (MD = - 0.08; 95% CI - 0.22 to 0.05) and HHS 6 months postoperatively (MD = 0.44; 95% CI - 0.11 to 1.00). This is the first meta-analysis comparing SuperPATH HA with CAs HA in patients with femoral neck fractures. SuperPATH HA was superior in the early short-term functional outcome (HHS) compared to CAs HA, reaching minimal clinically important differences. Furthermore, SuperPATH HA showed significantly better results in incision length, blood loss, time to mobilization, pain intensity (VAS), and hospitalization time than CAs HA.
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Fracturas del Cuello Femoral , Hemiartroplastia , Humanos , Hemiartroplastia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de Sangre Quirúrgica , Fracturas del Cuello Femoral/cirugía , Dolor/cirugía , Resultado del TratamientoRESUMEN
Apple pomace (AP), a by-product of the juice industry, is a rich and inexpensive source of natural bioactive substances, including phenolic compounds, that exhibit health-promoting effects. The recovery of these compounds from plant material using only classical extraction techniques and environmentally friendly solvents is often ineffective due to the entrapment of some compounds in the complex structures of plant cell walls. Lactic Acid Bacteria (LAB) fermentation can be a simple technology to increase the content of phenolic compounds, as well as the antioxidant activity of plant material. In this study, pomace from conventionally grown apples (Malus Domestica) of the Ligol cultivar were fermented with selected LAB strains (Lpb. plantarum KKP 3182, Lpb. plantarum KKP 1527, Lpb. plantarum ZFB 200), commercial starter cultures of Lpb. plantarum, and spontaneously. The fermented material was then subjected to ultrasound-assisted extraction, and the resulting extracts were analysed for their composition (phenolic compounds, triterpenoids, simple organic acids), and antioxidant activity. We found that: (1) the total phenolic content of AP extracts fermented with Lpb. plantarum KKP 1527 was about 30% higher than that of non-fermented AP extracts, (2) extracts of AP fermented with Lpb. plantarum KKP 1527 characterized a higher value of the antioxidant activity, (3) an increase in gallic acid procyanidin A2, protocatechuic acid, and procyanidin B2, while a decrease in rutin and quercetin was observed. The results indicated that AP fermented with Lpb. plantarum KKP 1527 may be a powerful and low-cost source of natural antioxidants which have applications in many industries.
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Lactobacillales , Lactobacillus plantarum , Malus , Malus/química , Antioxidantes/química , Lactobacillales/metabolismo , Fermentación , Lactobacillus plantarum/metabolismo , Fenoles/análisisRESUMEN
BACKGROUND: The validity of the PREDICT breast cancer prognostic model is unclear for young patients without adjuvant systemic treatment. This study aimed to validate PREDICT and assess its clinical utility in young women with node-negative breast cancer who did not receive systemic treatment. METHODS: We selected all women from the Netherlands Cancer Registry who were diagnosed with node-negative breast cancer under age 40 between 1989 and 2000, a period when adjuvant systemic treatment was not standard practice for women with node-negative disease. We evaluated the calibration and discrimination of PREDICT using the observed/expected (O/E) mortality ratio, and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, we compared the potential clinical utility of PREDICT for selectively administering chemotherapy to the chemotherapy-to-all strategy using decision curve analysis at predefined thresholds. RESULTS: A total of 2264 women with a median age at diagnosis of 36 years were included. Of them, 71.2% had estrogen receptor (ER)-positive tumors and 44.0% had grade 3 tumors. Median tumor size was 16 mm. PREDICT v2.2 underestimated 10-year all-cause mortality by 33% in all women (O/E ratio:1.33, 95%CI:1.22-1.43). Model discrimination was moderate overall (AUC10-year:0.65, 95%CI:0.62-0.68), and poor for women with ER-negative tumors (AUC10-year:0.56, 95%CI:0.51-0.62). Compared to the chemotherapy-to-all strategy, PREDICT only showed a slightly higher net benefit in women with ER-positive tumors, but not in women with ER-negative tumors. CONCLUSIONS: PREDICT yields unreliable predictions for young women with node-negative breast cancer. Further model updates are needed before PREDICT can be routinely used in this patient subset.
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Neoplasias de la Mama , Humanos , Femenino , Adulto , Pronóstico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Sistema de Registros , Países BajosRESUMEN
BACKGROUND: Our aim was to determine the best operative procedure in human participants with a displaced or non-displaced femoral neck fracture comparing cannulated screw (CS) fixation, dynamic hip screw (DHS) fixation, hemiarthroplasty (HA), and total hip arthroplasty (THA) in terms of surgical and functional outcomes, reoperation and postoperative complications. METHODS: We searched PubMed, The Cochrane Library, Clinical trials, CINAHL, and Embase for randomized controlled trials (RCTs) or quasi-RCTs up to 31 July 2022. A frequentist network meta-analysis was performed to assess the comparative effects of the four operative procedures, using fixed-effects and random-effects models. Mean differences (MDs) with 95% confidence intervals (CIs) were estimated for continuous variables and odds ratios (ORs) with 95% CIs were estimated for binary variables. RESULTS: A total of 33 RCTs with 5703 patients were included in our network meta-analysis. CS fixation was best in terms of operation time (CS: MD = - 57.70, 95% CI - 72.78; - 42.62; DHS: MD = - 53.56, 95% CI - 76.17; - 30.95; HA: MD = - 20.90, 95% CI - 30.65; - 11.15; THA: MD = 1.00 reference) and intraoperative blood loss (CS: MD = - 3.67, 95% CI - 4.44; - 2.90; DHS: MD = - 3.20, 95% CI - 4.97; - 1.43; HA: MD = - 1.20, 95% CI - 1.73; - 0.67; THA: MD = 1.00 reference). In life quality and functional outcome, measured at different time points with EQ-5D and the Harris Hip Score (HHS), THA ranked first and HA second (e.g. EQ-5D 2 years postoperatively: CS: MD = - 0.20, 95% CI - 0.29; - 0.11; HA: MD = - 0.09, 95% CI - 0.17; - 0.02; THA: MD = 1.00 reference; HHS 2 years postoperatively: CS: MD = - 5.50, 95% CI - 9.98; - 1.03; DHS: MD = - 8.93, 95% CI - 15.08; - 2.78; HA: MD = - 3.65, 95% CI - 6.74; - 0.57; THA: MD = 1.00 reference). CS fixation had the highest reoperation risk, followed by DHS fixation, HA, and THA (CS: OR = 9.98, 95% CI 4.60; 21.63; DHS: OR = 5.07, 95% CI 2.15; 11.96; HA: OR = 1.60, 95% CI 0.89; 2.89; THA: OR = 1.00 reference). CONCLUSION: In our cohort of patients with displaced and non-displaced femoral neck fractures, HHS, EQ-5D, and reoperation risk showed an advantage of THA and HA compared with CS and DHS fixation. Based on these findings, we recommend that hip arthroplasty should be preferred and internal fixation of femoral neck fractures should only be considered in individual cases. LEVEL OF EVIDENCE I: a systematic review of randomized controlled trials. TRIAL REGISTRATION: PROSPERO on 10 August 2022 (CRD42022350293).
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Artroplastia de Reemplazo de Cadera , Fracturas del Cuello Femoral , Hemiartroplastia , Humanos , Metaanálisis en Red , Fracturas del Cuello Femoral/cirugía , Tornillos Óseos , Fijación Interna de FracturasRESUMEN
Aim: Recently, the most commonly used for multiple breath washout device, the Exhalyzer D, has been shown to overestimate lung clearance index (LCI) results due to a software error. Our study aimed to compare the predictive values of LCI in the CF pulmonary exacerbations (PE) calculated with the updated (3.3.1) and the previous (3.2.1) version of the Spiroware software. Materials and Methods: The measurements were performed during 259 visits in CF pediatric patients. We used 39ΔPE pairs (PE preceded by stable visit) and 138ΔS pairs (stable visit preceded by stable visit) to compare the LCI changes during PE. The areas under the receiver operating curves (AUCROC) and odds ratios were calculated based on the differences between ΔPEs and ΔSs. The exacerbation risk was estimated using a logistic regression model with generalized estimating equations (GEE). Results: There were statistically significant differences in LCI 2.5% median values measured using the two versions of the software in the stable condition but not during PE. The AUCROC for changes between the two consecutive visits for LCI did not change significantly using the updated Spiroware software. Conclusions: Despite the lower median values, using the recalculated LCI values does not influence the diagnostic accuracy of this parameter in CF PE.
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PURPOSE: Neoadjuvant chemotherapy is standard of care in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), irrespective of the hormone receptor status. Trastuzumab-emtansine (T-DM1), antibody-drug conjugate, is highly effective in HER2+ EBC; however, no survival data are available for de-escalated antibody-drug conjugate-based neoadjuvant therapy without conventional chemotherapy. PATIENTS AND METHODS: In the WSG-ADAPT-TP (ClinicalTrials.gov identifier: NCT01779206) phase II trial, 375 centrally reviewed patients with hormone receptor-positive (HR+)/HER2+ EBC (clinical stage I-III) were randomly assigned to 12 weeks of T-DM1 with or without endocrine therapy (ET) or trastuzumab + ET once every 3 weeks (ratio 1:1:1). Adjuvant chemotherapy (ACT) omission was allowed in patients with pathologic complete response (pCR). In this study, we report the secondary survival end points and biomarker analysis. Patients who received at least one dose of study treatment were analyzed. Survival was analyzed using the Kaplan-Meier method, two-sided log-rank statistics, and Cox regression models stratified for nodal and menopausal status. P values < .05 were considered statistically significant. RESULTS: T-DM1, T-DM1 + ET, and trastuzumab + ET induced similar 5-year invasive disease-free survival (iDFS; 88.9%, 85.3%, 84.6%; Plog-rank = .608) and overall survival rates (97.2%, 96.4%, 96.3%; Plog-rank = .534). Patients with pCR versus non-pCR had improved 5-year iDFS rates (92.7% v 82.7%; hazard ratio, 0.40 [95% CI, 0.18 to 0.85]). Among the 117 patients with pCR, 41 did not receive ACT; 5-year iDFS rates were similar in those with (93.0% [95% CI, 84.0 to 97.0]) and without ACT (92.1% [95% CI, 77.5 to 97.4]; Plog-rank = .848). Translational research revealed that tumors with PIK3CA wild type, high immune marker expression, and luminal-A tumors (by PAM50) had an excellent prognosis with de-escalated anti-HER2 therapy. CONCLUSION: The WSG-ADAPT-TP trial demonstrated that pCR after 12 weeks of chemotherapy-free de-escalated neoadjuvant therapy was associated with excellent survival in HR+/HER2+ EBC without further ACT. Despite higher pCR rates for T-DM1 ± ET versus trastuzumab + ET, all trial arms had similar outcomes because of mandatory standard chemotherapy after non-pCR. WSG-ADAPT-TP demonstrated that such de-escalation trials in HER2+ EBC are feasible and safe for patients. Patient selection on the basis of biomarkers or molecular subtypes may increase the efficacy of systemic chemotherapy-free HER2-targeted approaches.
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Neoplasias de la Mama , Inmunoconjugados , Humanos , Femenino , Trastuzumab , Neoplasias de la Mama/patología , Ado-Trastuzumab Emtansina/uso terapéutico , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inmunoconjugados/uso terapéuticoRESUMEN
INTRODUCTION: This study aims to quantify surgical site complications (SSC) after isolated salvage neck dissection (ND) compared with primary ND. PATIENTS AND METHODS: Between 1997 and 2017 in the Netherlands Cancer Institute - Antoni van Leeuwenhoek, a total of 323 isolated NDs were performed in 308 patients: primary ND (n = 144), post-radiotherapy (RT) ND (n = 53) and post-chemoradiotherapy (CRT) ND (n = 126). Patient, tumor and therapy characteristics were recorded. SSCs were scored according to the Clavien-Dindo Classification (CDC). RESULTS: 101 NDs (31%) were complicated by at least one SSC. In total, 189 different SSCs occurred. Translated to CDC, 45 complications were grade 2, 25 grade 3a and 31 grade 3b. No significant difference in occurrence of SSC (CDC >1) was found between all groups. However, post-CRT, selective (SND) and modified radical ND and radical ND (MRND/RND) (p = 0.005), resection of sternocleidomastoid muscle (SCM) (p = 0.039) and duration of super selective ND surgery (p = 0.048) were significantly associated with more SSC. SCM muscle removal was associated with more surgical site infection (p = 0.045) and necrosis (p = 0.036). From week 10 post-RT/CRT, no difference in complication frequency with primary ND was seen. CONCLUSION: Post-CRT SND, MRND/RND and SCM muscle resection were associated with an increased incidence of SSCs. If oncologically possible, limit the extent of ND and when an MRND is inevitable, preserve the SCM muscle for optimal prevention of SSC. Concerning SSC, optimal timing of salvage ND is minimal 10 weeks after RT/CRT.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Disección del Cuello/efectos adversos , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Quimioradioterapia/efectos adversos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Estudios de CohortesRESUMEN
PURPOSE: Previous efforts to predict absolute risk of treatment-related cardiovascular diseases (CVDs) have mostly focused on childhood cancer survivors. We aimed to develop prediction models for risk of coronary heart disease (CHD) and heart failure (HF) for survivors of adolescent/adult Hodgkin lymphoma (HL). METHODS: For model development, we used a multicenter cohort including 1,433 5-year HL survivors treated between 1965 and 2000 and age 18-50 years at HL diagnosis, with complete data on administered chemotherapy regimens, radiotherapy volumes and doses, and cardiovascular follow-up. Using cause-specific hazard models, covariate-adjusted cumulative incidences for CHD and HF were estimated in the presence of competing risks of death because of other causes than CHD and HF. Age at HL diagnosis, sex, smoking status, radiotherapy, and anthracycline treatment were included as predictors. External validation for the CHD model was performed using a Canadian cohort of 708 HL survivors treated between 1988 and 2004 and age 18-50 years at HL diagnosis. RESULTS: After a median follow-up of 24 years, 341 survivors had developed CHD and 102 had HF. We were able to predict CHD and HF risk at 20 and 30 years after treatment with moderate to good overall calibration and moderate discrimination (areas under the curve: 0.68-0.74), which was confirmed by external validation for the CHD model (areas under the curve: 0.73-0.74). On the basis of our model including prescribed mediastinal radiation dose, 30-year risks ranged from 4% to 78% for CHD and 3% to 46% for HF, depending on risk factors. CONCLUSION: We developed and validated prediction models for CHD and HF with good overall calibration and moderate discrimination. These models can be used to identify HL survivors who might benefit from targeted screening for CVD and early treatment for CVD risk factors.
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Enfermedades Cardiovasculares , Enfermedad Coronaria , Insuficiencia Cardíaca , Enfermedad de Hodgkin , Adulto , Adolescente , Humanos , Niño , Adulto Joven , Persona de Mediana Edad , Enfermedad de Hodgkin/terapia , Canadá , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/epidemiología , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedad Coronaria/complicacionesRESUMEN
Ataxia-telangiectasia (A-T) is a severe syndromic neurodegenerative inborn error of immunity characterized by DNA reparation defect, chromosomal instability, and hypersensitivity to ionizing radiation, thereby predisposing affected individuals to malignant transformation. While the leading disease symptomatology is associated with progressively debilitating cerebellar ataxia accompanied by central and peripheral nervous system dysfunctions, A-T is a multisystemic disorder manifesting with the heterogeneity of phenotypic features. These include airway and interstitial lung disease, chronic liver disease, endocrine abnormalities, and cutaneous and deep-organ granulomatosis. The impaired thymic T cell production, defective B cell development and antibody production, as well as bone marrow failure, contribute to a combined immunodeficiency predisposing to infectious complications, immune dysregulation, and organ-specific immunopathology, with the A-T hyper-IgM (HIGM) phenotype determining the more severe disease course. This study aimed to clarify the immunodeficiency and associated immune dysregulation as well as organ-specific immunopathology in children with A-T. We also sought to determine whether the hyper-IgM and non-hyper-IgM phenotypes play a discriminatory role and have prognostic significance in anticipating the clinical course and outcome of the disease. We retrospectively reviewed the medical records of twelve A-T patients, aged from two to eighteen years. The patients' infectious history, organ-specific symptomatology, and immunological workup including serum alpha-fetoprotein, immunoglobulin isotypes, IgG subclasses, and lymphocyte compartments were examined. For further comparative analysis, all the subjects were divided into two groups, HIGM A-T and non-HIGM A-T. The clinical evaluation of the study group showed that recurrent respiratory tract infections due to viral and bacterial pathogens and a chronic obstructive airway disease along with impaired humoral immunity, in particular complete IgA deficiency, were noted in all the A-T patients, with both HIGM and non-HIGM phenotypes. The most important features with the discriminatory role between groups, were autoimmune disorders, observable four times more frequently in HIGM than in non-HIGM A-T. Two patients with the HIGM A-T phenotype were deceased due to liver failure and chronic Epstein-Barr virus (EBV) infection. It may therefore be assumed that the HIGM form of A-T is associated with more profound T cell dysfunction, defective immunoglobulin class switching, chronic EBV expansion, and poorer prognosis.
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Fermentation of two red beet cultivars (Wodan and Alto) with single-strain starter cultures consisting of selected strains of lactic acid bacteria (LAB) of plant origin (Weissella cibaria KKP2058, Levilactobacillus brevis ZF165) and a multi-strain culture (containing W. cibaria KKP2058, L. brevis ZF165, Lactiplantibacillus plantarum KKP1822, Limosilactobacillus fermentum KKP1820, and Leuconostoc mesenteroides JEIIF) was performed to evaluate their impact on betalains, free amino acids, formation of biogenic amines, and antioxidative properties of the juice formed. Next-generation sequencing data analysis used to identify the microbial community revealed that the starter cultures promoted the dominance of the genus Lactobacillus, and decreased the proportion of spoilage bacteria compared to spontaneously fermented juices. Generally, the fermentation process significantly influenced the amount of the analyzed compounds, leading in most cases to their reduction. The observed changes in the studied parameters depended on the starter culture used, indicating different metabolic activities of the LAB strains towards bioactive compounds. The use of multi-strain starter cultures allowed to largely prevent the reduction of betacyanins and histamine formation.
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Antioxidantes , Lactobacillales , Antioxidantes/metabolismo , Aminoácidos/metabolismo , Microbiología de Alimentos , Polonia , Aminas Biogénicas/metabolismo , Lactobacillales/genética , Lactobacillales/metabolismoRESUMEN
PURPOSE: Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemotherapy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial. EXPERIMENTAL DESIGN: ADAPT-TN is a randomized neoadjuvant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with pathological complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regarding selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL). RESULTS: After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68-1.59]. Additional anthracycline-containing chemotherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41-4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis. CONCLUSIONS: Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs. See related commentary by Sharma, p. 4840.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Terapia Neoadyuvante/efectos adversos , Carboplatino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Análisis de SupervivenciaRESUMEN
Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg-1 and nivolumab 3 mg kg-1. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3-4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab.
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Melanoma , Neoplasias Cutáneas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Ipilimumab , Melanoma/tratamiento farmacológico , Melanoma/patología , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Nivolumab , Calidad de Vida , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
Infections and infectious complications are hallmarks of common variable immunodeficiency (CVID) and the leading cause of morbidity and mortality in affected patients at any age. However, the pediatric CVID is no longer perceived as a primary immunodeficiency associated solely with infectious manifestations; autoimmune, allergic, lymphoproliferative, and malignant disorders and organ-specific immunopathology also characterize the spectrum of non-infectious complications. In this study, we sought to determine the role of immune dysregulation and frequency of non-infectious sequelae in children affected with CVID. We also aimed at providing an insight into the pathogenesis of non-infectious complications and at delineating the diagnostic approach to pediatric CVID with immune dysregulation. An in-depth retrospective analysis of clinical manifestations and their correlations with selected immune parameters was performed in a group of 39 CVID children, followed by our pediatric immunology department. Whereas recurrent sinopulmonary infections were present in all (100%) of the children studied, an unexpectedly high rate of non-infectious disorders and immune dysregulation phenotypes were observed in as many as 32 (82.05%) patients, compared with infection-only phenotypes limited to 7 (17.95%) male patients. The most common inflammatory comorbidity was asthma, diagnosed in 21 (53.85%) patients. The second most frequent immune dysregulation group was autoimmune disorders, present in 18 (46.15%) of the children studied with a high rate of autoimmune thyroiditis in as many as 10 (25.64%) of the CVID-affected children. Lymphoproliferation was seen in 14 children (35.90%), and, among them, lymphadenopathy occurred in nine (23.08%) cases and granulomatous lymphocytic interstitial lung disease in seven (17.95%) cases. Finally, malignancies occurred in two female patients (5.13%), papillary thyroid cancer in the first one and T-cell lymphoblastic leukemia in the other one. The most prominent abnormalities in the B- and T-cell compartment contributing to complex immune deficiency and immune dysregulation phenotypes were seen in the autoimmunity group, showing significant reductions in the switched memory B cell, naive T helper cell, and regulatory T-cell subsets. Herein, we document the previously unreported high rate of immune dysregulation in pediatric CVID as a clinical and diagnostic challenge with the variability of defects in the humoral and cellular immune responses.
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PURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies.