Efectividad de tres métodos de desobturación sobre modelos réplica / Effectiveness of three unsealing methods on replica models

El objetivo fue evaluar la eficacia de remoción del material de obturación y el tiempo empleado para la desobturación con tres métodos diferentes, en modelos réplica. Se utilizaron 24 modelos réplica de premolares inferiores instrumentados con sistema Protaper Gold hasta F4, irrigación NaOCl 2,5% y ED-TAC 17%. Obturación termoplastizada sistema Fast Pack Pro. La muestra (n=24) se dividió aleatoriamen-te en tres grupos experimentales (n=8) sometidos a distintos métodos de desobturación. Grupo 1: fresas Gates Glidden II/III y limas Hedstroem. Grupo 2: lima Medium sistema Wave One Gold y punta ultrasóni-ca Ultra X, (Eighteeth). Grupo 3: lima Rotate 35/04 y punta ultrasónica R1 Clearsonic, (Helse). Se midió el tiempo de desobturación. Las piezas se radiogra-fiaron con radiovisiógrafo digital RVG 5200 (Cares-tream), y fueron procesadas con software Image-J. Al analizar cantidad de material de obturación rema-nente, la prueba de Kruskal-Wallis (p<0,05), mostró diferencias estadísticamente significativas entre grupos 2 y 3. Grupo 1 no mostró diferencias signifi-cativas con los otros dos (p>0,05). Al analizar tiempo de desobturación, el test de Kruskal-Wallis no deter-minó diferencias significativas entre grupos 1 y 2 (p>0,05), el grupo 3 tuvo diferencias estadísticamen-te significativas con los grupos 1 y 2 (p<0,05). En con-clusión, ninguno de los sistemas de desobturación evaluados logró eliminar la totalidad del material de obturación. El que combinó limas rotatorias con punta ultrasónica de retratamiento fue el que mos-tró mayor efectividad de remoción y demandó menor tiempo de trabajo (AU)

Objective: to evaluate the effectiveness of obturation material removal and the time that the procedure took, when performing the retreatment with three different methods, in replica models of mandibular premolars. Materials and methods: 24 replica models of lower premolars instrumented with Protaper Gold system up to F4, 2.5% NaOCl irrigation and 17% ED-TAC were used. Thermoplastized sealing with Fast Pack Pro system. The sample (n=24) was randomly divided in three experimental groups (n=8) subjected to different unsealing methods. Group 1: Gates Glid-den burs II and III and Hedstroem files. Group 2: Wave One Gold Medium file system and Ultra X ultra-sonic tip, (Eighteeth). Group 3: Rotate 35/04 file and R1 Clearsonic ultrasonic tip (Helse). Unsealing time was measured. The samples were radiographed with a digital radiovisiograph RVG 5200 (Carestream), and processed with Image-J software. When analyzing the amount of remaining filling material, Kruskal-Wallis test showed statistically significant differences be-tween groups 2 and 3 (p<0,05). Group 1 did not show significant differences with the other two (p>0,05). When analyzing unsealing time, Kruskal-Wallis test determined that there were no significant differ-ences between groups 1 and 2 (p>0,05), but group 3 had statistically significant differences with the other two (p<0.05). None of the unsealing systems evalu-ated managed to eliminate all of the sealing material. The group that combined rotary files with ultrasonic retreatment tip showed the greatest removal effec-tiveness and required less work time (AU)

Lesiones perirradiculares persistentes: revisión narrativa / Persistent periradicular lesions: a narrative review

La persistencia de lesiones perirradiculares luego del tra- tamiento endodóntico es un problema que requiere del clínico un conocimiento cabal de la histofisiología y de la histopato- logía del sistema de conductos radiculares del tejido pulpar y de los tejidos perirradiculares (periodonto y hueso); además de considerar siempre la posible existencia de enfermedades sistémicas que también pueden actuar como factores de in- fluencia. La presencia de bacterias remanentes a posteriori del tratamiento es considerada como una de las causas principales y más frecuentes para la perpetuación de las lesiones perirra- diculares. Sin embargo, existen otros factores causales, como la existencia de conductos laterales o accesorios infectados y no tratados, la reabsorción dentinaria interna, intercomunica- ciones, cul-de-sacs o istmos; que representan áreas de difícil acceso durante la instrumentación e irrigación. Cuando la cau- sa original se localiza en la zona perirradicular, como en los casos de actinomicosis, reacciones a cuerpo extraño, cristales de colesterol (CRCo) y granulomas o quistes con alto conte- nido de CRCo, la indicación más adecuada es el retratamiento y la cirugía periapical como complemento (AU)

The persistence of periradicular lesions after endodontic treatment is a problem that requires the doctor to have a thor- ough knowledge of the histophysiology and histopathology of the root canal system, the pulp tissue and periradicular tis- sues (periodontium and bone); as well as always considering the possible existence of systemic alterations that can also be influencing factors. Persisting bacteria within the root canal system after treatment is one of the major and most frequent causes for the perpetuation of periradicular lesions. Howev- er, there are other possible causal factors such as the exist- ence of untreated lateral or accessory canals, internal dentin resorption, intercommunications, cul-de-sacs or isthmuses; areas that represent a difficulty in access during instrumen- tation and irrigation. If the original cause is located in the periradicular area, in cases like actinomycosis, foreign-body reactions, cholesterol crystals (CRCo) and granulomas or cysts with high content of CRCo, retreatment coupled with periapical surgery is the best approach to treatment (AU)

Diagnosis and Management of Multiple Myeloma: A Review.

IMPORTANCE: Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year. OBSERVATIONS: Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers ß2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients. CONCLUSIONS AND RELEVANCE: Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

Does MOSES pulse modulation reduce short-term catheter reinsertion following holmium laser enucleation of the prostate?

PURPOSE: Previously published studies have shown small prostate size, capsular perforation and intraoperative bladder distension are associated with failed trial without a catheter (TWOC) after HoLEP. The study objective was to determine the relationship between MOSES pulse modulation versus standard laser technology and short-term catheter reinsertion following failed TWOC. MATERIALS AND METHODS: The study included 487 patients who underwent HoLEP, using standard holmium laser settings (180 patients) or MOSES pulse modulation (255 patients), between August 2018 and February 2021. Catheter reinsertion defined as reinsertion following failed TWOC within 30 days of surgery. Association of pulse modulation with catheter reinsertion was examined using single and multivariable logistic regression models. Comparisons of pre and intraoperative characteristics between patients treated without and with pulse modulation were made using a Wilcoxon rank sum test for numeric characteristics or Fisher's exact test for categorical characteristics. RESULTS: Short-term catheter reinsertion occurred in 14% (26/180) of the standard laser setting group as compared with 10% (24/252) of the pulse modulation group. There was no statistically significant association with short-term catheter reinsertion in single (unadjusted OR [standard settings vs. pulse modulation], 1.60; 95% CI, 0.80-2.91; p=0.12) or multivariable analysis adjusting for specimen weight and operative time (adjusted OR [standard settings vs. pulse modulation], 1.44; 95% CI, 0.77-2.68; p=0.25). CONCLUSIONS: In this study, we found no association between post-HoLEP short-term catheter reinsertion following failed TWOC and MOSES pulse modulation. Although MOSES pulse modulation offers several well-documented advantages, catheter reinsertion events appear to be attributable to other factors.

Primary signet ring cell carcinoma of the uterine cervix: A case report.

RATIONALE: Primary signet ring cell carcinoma of the uterine cervix is extremely rare and the clinical characteristics and prognosis are not well known and there are no specific guidelines for treatment. PATIENT CONCERNS: A 43-year-old woman was referred to our hospital for abnormal uterine bleeding lasting 1 month. DIAGNOSES: Histological examination revealed a signet ring cell carcinoma of the uterine cervix. After evaluation of extragenital origin, the patient was diagnosed International Federation of Gynecology and Obstetrics stage IIIC1 primary signet ring cell carcinoma or the uterine cervix. INTERVENTION: The patient was prescribed concomitant chemo-radiation followed by intracavitary brachytherapy. OUTCOMES: She showed no evidence of disease after treatment but, it recurred after 7 months of last treatment. LESSONS: Different approaches to diagnosis and treatment of this rare disease are needed and molecular pathological studies related to the onset of the disease are required.

Successful retreatment with erlotinib after erlotinib-related interstitial lung disease.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors are effectively being used in the treatment of non-small cell lung cancer. Although most of their adverse effects are mild to moderate, they occasionally can cause life-threatening interstitial lung disease. We aimed to present a case of lung adenocarcinoma successfully re-treated with erlotinib after recovery with effective treatment of erlotinib-induced interstitial lung disease. CASE DESCRIPTION: A 54-year-old nonsmoking woman was diagnosed with metastatic adenocarcinoma of the lung. After progression with first-line chemotherapy, erlotinib 150 mg daily was initiated. On the 45th day of erlotinib treatment, interstitial lung disease occurred and erlotinib was discontinued. Clinical improvement was achieved with dexamethasone treatment and erlotinib was re-initiated. Ten weeks after re-initiation of erlotinib, 100 mg daily partial response was observed. CONCLUSIONS: Incidence of interstitial lung disease is higher in men, smokers, and patients with pulmonary fibrosis. Interstitial lung disease radiologically causes ground-glass opacity and consolidation. The physician should quickly evaluate new respiratory symptoms in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors, discontinue the epidermal growth factor receptor tyrosine kinase inhibitor treatment, and initiate corticosteroids if clinical diagnosis is interstitial lung disease.

SEOM clinical guideline for management of adult medulloblastoma (2020).

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Real-World Treatment of Patients With Relapsed/Refractory Myeloma.

The continuous advances in the treatment landscape of multiple myeloma has led to the approval of several novel agents and their combinations that significantly improved patient outcomes. Despite their undoubtful effectiveness in the context of clinical trials, their impact on real-world (RW) clinical practice remains debatable. RW data on the role of novel agents and their combinations among patients with relapsed/refractory multiple myeloma have confirmed the efficacy of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. However, the magnitude of the benefit and the safety profile may differ among RW studies and between RW and pivotal clinical trials. Several variables may pertain to these observations and include patient selection, ethnicity, age, comorbidities, disease stage at diagnosis and at relapse, number of prior lines of therapy, disease subtype, presence of renal impairment, extramedullary disease, and cytogenetic abnormalities. All these contribute to a varying degree of disease and patient heterogeneity among the studies that may result in a differential treatment effect. The expertise of each medical center and the treatment setting in terms of availability and drug access are particularly important as well. Interestingly, RW observations may serve as proof of concept for designing novel clinical trials, as is the case with retreatment studies. In conclusion, clinical trial and RW data are complementary, and they should be considered to improve both clinical trial design and clinical practice.

O uso da tomografia computadorizada de feixe cônico no diagnóstico e no gerenciamento de insucesso endodôntico: relato de caso clínico / The use of cone beam computed tomography in the diagnosis and management of endodontic failure: clinical case report

Objetivo: descrever um caso clínico em que a tomografia computadorizada de feixe cônico (TCFC) foi utilizada para auxiliar no diagnóstico e no melhor gerenciamento de retratamento endodôntico. Relato de caso: uma paciente compareceu à clínica com queixa de uma fístula na região dos molares superiores do lado direito há aproximadamente dois meses. Radiograficamente, observou-se lesão periapical do elemento 17. Após a confirmação da necessidade do retratamento, a paciente relatou já ter feito duas intervenções endodônticas nesse elemento. Assim, optou-se por solicitar um exame de TCFC, para melhores diagnóstico e planejamento do caso. Ao avaliar a TCFC, verificou-se presença de lesão periapical extensa, presença de espaços vazios no canal mesiovestibular (MV) e palatino (P), cone de guta percha além do ápice no canal distovestibular (DV) e localização do canal mesiopalatino (MP), que não havia sido manuseado anteriormente, rompimento de cortical óssea vestibular e palatino. Após planejamento, a paciente foi submetida ao retratamento endodôntico. Foi realizada a desobstrução dos canais radiculares com remoção do cone ultrapassando no canal DV, localização do MP e instrumentação completa de todos os canais. O hidróxido de cálcio foi utilizado como medicamento intracanal entre as consultas. Ao observar a regressão da fistula e os canais sem presença de exsudato, realizou-se a obturação do canal radicular. Considerações finais: a TCFC permitiu a visualização de erros operatórios pertinentes ao caso durante os tratamentos endodônticos prévios, o que possibilitou a indicação de um novo tratamento endodôntico e a manutenção do dente na arcada dentária.(AU)

Objective: to describe a clinical case where cone beam computed tomography (CBCT) was used to assist in the diagnosis and better management of endodontic retreatment. Case report: the patient attended the clinic complaining of a fistula in the upper molar region on the right side for approximately two months. Radiographically, the presence of a periapical lesion of element 17 was observed. After confirming the need for retreatment, the patient reported having already undergone two endodontic interventions on this tooth. Thus, it was decided to request a CBCT exam for better diagnosis and case planning. When assessing the CBCT, there was the presence of extensive periapical lesion, presence of empty spaces in the mesiobuccal (MB) and palatal (P) canal, gutta percha cone beyond the apex in the distobuccal (DB) canal and location of the mesiopalatal (MP) canal - which had not been previously handled -, rupture of the cortex vestibular and palatal bone. After planning, the patient underwent endodontic retreatment. Then, all the previous filling material were removed, including the gutta-percha by passing into the DB canal, MP was localized and complete instrumentation of all root canals were done. Calcium hydroxide was used as an intracanal medication between appointments. When the regression of the fistula was observed and canals were without exudate, root canal filling was performed. Final considerations: the CBCT allowed the visualization of operative errors pertinent to the case during previous endodontic treatments, which allowed the indication of a new endodontic treatment and the maintenance of the tooth in the dental arch.(AU)

Value of early second session shock wave lithotripsy in treatment of upper ureteric stones compared to laser ureteroscopy.

PURPOSE: The safety and efficacy of early second session shock wave lithotripsy (SWL) compared with laser ureteroscopy (URS) for the treatment of upper ureteric stones were evaluated. METHODS: From January to October 2019, 108 patients with upper ureteric stones (< 1.5 cm and ≤ 1000 Hounsfield unit (HU)) were randomized into SWL and laser URS groups. The second SWL session was performed within 48-72 h of the first session. Using plain abdominal X-ray and ultrasonography, patients were evaluated 48-72 h after the first SWL session and one week after the second and third SWL sessions or one week after URS. The procedure was considered a success when no additional procedures were needed to clear the stone. To determine the stone-free rate (SFR), noncontrast computed tomography of the urinary tract was performed three months postoperatively. RESULTS: In the SWL group, the success rates were 92.6% and 94.4% after the second and third sessions. The SFR was 96.2% in the laser URS group. The success rates were not significantly different between the second and third SWL sessions versus the laser URS (p = 0.418 and 0.660, respectively). Operative and fluoroscopy times were significantly longer in the SWL group (p = 0.001), and JJ stent insertions were needed after laser URS. CONCLUSION: Ultraslow full-power SWL treatment of patients with upper ureteric stones (< 1.5 cm and ≤ 1000 HU) with an early second session is safe and effective compared to laser URS. Patients who do not respond to early second SWL session should be shifted to another treatment modality.

Factors associated with extubation failure in very low birth weight infants: a cohort study in the northeast Brazil.

OBJECTIVES: Identifying and understanding the main risk factors associated with extubation failure of very low birthweight (VLBW) infants in different populations can subsequently help in establishing better criteria while taking decision of extubation. The aim of the study was to identify factors associated with extubation failure in VLBW infants. METHODS: A cohort study of VLBW infants who underwent their first extubation between April 2018 and December 2019 in a Neonatal Intensive Care Unit, Alagoas, Brazil, were included in this study. Extubation failure was defined as reintubation within seven days of extubation. Relative risks of predictive variables different between the extubation success group (ES) and extubation failure group (EF) were estimated with a robust Poisson regression model. RESULTS: Out of the 112 infants included, 26 (23%) cases exhibited extubation failure. Extremely low birth weight (RR 2.55, 95% CI 1.07, 6.06), mechanical ventilation duration for first extubation greater than seven days (RR 2.66, 95% CI 1.10, 6.45), vaginal delivery (RR 2.07, 95% CI 1.03, 4.18) and maternal chorioamnionitis (RR 4.89, 95% CI 1.26-18.98) remained independently associated with extubation failure. EF had a significant greater need for respiratory support, longer oxygen therapy duration, more bronchopulmonary dysplasia (BPD) and longer length of hospital stay, even when adjusted for confounding variables. CONCLUSIONS: Extremely low birth weight infants needing mechanical ventilation, wherein the duration for first extubation was longer than seven days, with vaginal delivery and maternal chorioamnionitis failed more frequently at the first attempt of extubation. And this failure increased the risk of BPD and the length of hospital stay.

Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICI) have transformed the standard care of cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal potential which lead to permanent interruption of immunotherapy. OBJECTIVES: To characterize ICI-mediated myocarditis and re-introduction to immunotherapy. METHODS: During 2019, 849 patients were treated with ICI at Tel Aviv Sourasky Medical Center for the diagnosis of lung adenocarcinoma, gastric adenocarcinoma, urothelial carcinoma, and hepatocellular carcinoma. Overall, seven (0.8%) patients were diagnosed with ICI-mediated myocarditis, according to the European Society of Cardiology guidelines of myocarditis 2013. We retrospectively evaluated their presentation, severity, and clinical outcomes. RESULTS: Among the seven patients, only one had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody. All patients were treated with single-agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical cardiac magnetic resonance; however, only three had reduced ejection fraction. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I and II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden. The one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and, therefore, therapy was interrupted permanently. CONCLUSIONS: ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life-saving cancer therapy. The current data suggest that re-introduction may be considered in low-grade patients; however, a better definition of the diagnosis and grading is needed.

Predicting the need for retreatment in venous sinus stenting for idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension is a disease of raised intra-cranial pressure of unknown etiology. Lateral cerebral venous sinus stenosis (VSS) has been increasingly reported in these patients, and stenting has emerged as an alternative treatment for medically refractory symptoms. Treatment efficacy on meta-analysis appears promising, but identifying which patients are likely to benefit most, and which are likely to require repeat procedures, is currently unclear. METHODS: We retrospectively reviewed a prospectively collected database of 79 patients treated with venous sinus stenting at a single academic center with minimum follow-up of 18 months. We extracted baseline clinical data, as well as manometry at lumbar puncture and during angiography, and used logistic regression to identify parameters that could predict stent failure. RESULTS: Retreatment rate after successful VSS was 13.9%. Lumbar puncture opening pressure (OP) was shown to significantly predict treatment failure (ß=0.06; OR=1.064 (1.003-1.135); P=0.039). This effect remained significant when age, sex and body mass index were added to the model (ß=0.06; OR=1.066 (1.002-1.140); P=0.043). OP was correlated with venous sinus manometry readings in the superior sagittal and transverse sinus pre-stent placement, as well trans-stenotic gradient (P<0.001). CONCLUSIONS: Higher lumbar puncture OP was associated with an increased risk of stent failure in transverse sinus stenting for idiopathic intracranial hypertension, although the performance of this model as a linear discriminator was poor. Further studies are required to better assess which patients are at greatest risk of treatment failure.

Comparison of efficacy of HCAG and CAG re-induction chemotherapy in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia.

PURPOSE: The present study aimed to investigate the efficacy and severity of adverse effects of HCAG and CAG re-induction chemotherapy in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia (AML) following induction failure. METHODS: A total of 94 AML patients were enrolled in the study, of whom 46 were treated with HCAG chemotherapy, while 48 were treated with CAG chemotherapy. RESULT: The complete remission (CR) was 39.6% in the patients with HCAG, while the CR was 33.3% in the CAG group. The overall remission (ORR) was 63.0% and 43.5% in patients of the HCAG and CAG groups, respectively (P = 0.038). The median survival time of progression free survival (PFS) was 8.0 (95% CI 3.843-10.157) months in the HCAG group and 7.0 (95% CI 2.682-13.318) months in the CAG group (P = 0.032). A total of 31 patients in the HCAG group suffered from grade 4 hematological toxicity, whereas 29 patients were treated with CAG (P = 0.622). A total of 27 (58.7%) cases indicated apparent pulmonary infection in the HCAG group, while 25 (52.1%) were noted with this complication in the CAG group (P = 0.519). Oral cavity toxicity was evident for 13 (28.3%) and 11 (23.0%) cases in the HCAG and CAG groups, respectively (P = 0.216). CONCLUSION: The HCAG regimen was more effective than the CAG regimen in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia although the HCAG regimen exhibited similar toxicity with that of the CAG group.

Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations.

BACKGROUND: The main goal of management in patients with non-small cell lung cancer (NSCLC) and malignant pleural effusion (MPE) is palliation. Patients with MPE and actionable mutations, because their disease is expected to respond quickly and markedly to targeted therapy, are less likely than those without actionable mutations to receive definitive MPE management. Whether such management is indicated in these patients is unclear. RESEARCH QUESTIONS: What is the time to ipsilateral MPE recurrence requiring intervention in patients with metastatic NSCLC by mutation status? What are the risk factors for MPE recurrence? STUDY DESIGN AND METHODS: Retrospective cohort study of consecutive patients who underwent initial thoracentesis for MPE. We used a Fine-Gray subdistribution hazard model to calculate the time to ipsilateral MPE recurrence requiring intervention within 100 days of initial thoracentesis and to identify variables associated with time to pleural fluid recurrence. RESULTS: A total of 396 patients, comprising 295 (74.5%) without and 101 (25.5%) with actionable mutations, were included. Most patients with actionable mutations (90%) were receiving targeted treatment within 30 days of initial thoracentesis. On univariate analysis, patients with actionable mutations showed a significantly higher hazard of MPE recurrence. On multivariate analysis, this difference was not significant. Larger pleural effusion size on chest radiography (P < .001), higher pleural fluid lactate dehydrogenase (P < .001), and positive cytologic examination results (P = .008) were associated with an increased hazard of recurrence. INTERPRETATION: Our findings indicate that patients with actionable mutations have a similar risk of MPE recurrence when compared with patients without mutations and would benefit from a similar definitive management approach to MPE.

Literature meta-analysis about the efficacy of re-challenge with PD-1 and PD-L1 inhibitors in cancer patients.

INTRODUCTION: Immune checkpoint inhibitor (ICPis) re-challenge could be an attractive therapeutic option considering its good safety profile. However, little data is available regarding anti-PD-1/anti-PD-L1 retreatment. We conducted a meta-analysis focusing on outcomes of solid cancer patients performing this strategy. METHODS: Fourteen full papers involving 74 patients were included. Individual data about best response or progression-free survival (PFS) upon the first and second course of anti-PD-1/anti-PD-L1 were collected. RESULTS: Non-small-cell lung cancer (53%) and melanoma (34%) were the most represented cancers. Higher objective response (46% versus 24%, P=4.10-4) and disease control rates (73% versus 52%, P=7.10-3) were obtained upon the first ICPi course compared to re-challenge. No association between responses obtained with the two ICPis courses was found (P=3.10-1). The PFS upon the first ICPi (PFS1) was longer than after re-challenge (PFSR) (6.6 versus 2.8 months, hazard ratio (HR) 0.57, P=2.10-3). A longer PFSR was obtained in patients with a longer PFS1 (P=6.10-3), in those who discontinued the first ICPi due to toxicity or per protocol (8.8 versus 2.1 months if disease progression occurs, P=2.10-3), and in those not receiving intercalated treatment between the two ICPis (6.6 versus 2.1 months for the treated ones, P=1.10-3). DISCUSSION: Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period.

Carboplatin re-treatment in platinum-resistant epithelial ovarian cancer patients.

PURPOSE: Treatment of multi-resistant epithelial ovarian cancer represents a clinical challenge with limited choices. Anti-angiogenic therapy has shown great potential in combination with frontline-therapy. Studies investigating heavily pre-treated patients are few. This study investigated the effect of re-treating patients with carboplatin combined with bevacizumab and cell-free DNA (cfDNA) as a potential predictor of outcome. METHODS: This single-center study enrolled 73 multi-resistant ovarian cancer patients from 2008 to 2015. Patients were treated with a combination of bevacizumab (10 mg/kg) and carboplatin (AUC5) every 3 weeks. Baseline plasma samples were analyzed for cfDNA levels. Treatment response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and CA125 blood values. RESULTS: The response rate according to RECIST and/or CA125 was 57%. Median number of cycles was 6. The median progression-free survival and overall survival was 5.0 and 11.2 months, respectively. Eighteen patients developed allergic reactions to carboplatin. Patients were grouped into two cfDNA-groups according to median value. The cfDNA value was correlated to progression-free survival (PFS, p = 0.015), but not to overall survival (OS, p = 0.067) in the univariate analysis. In the multivariate analysis both PFS and OS were highly correlated to the levels of cfDNA (PFS, hazard ratio = 1.87, p = 0.012; OS, hazard ratio = 1.67, p = 0.037) with patients with high levels of cfDNA having poorest outcome. CONCLUSION: Our results might provide guidance in cases with heavily pre-treated patients, where alternatives are limited. Carboplatin and bevacizumab treatment should be weighed against best supportive care, current non-platinum therapies and experimental treatment. cfDNA seems to offer prognostic insight.