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1.
Swiss Med Wkly ; 150: w20246, 2020 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-32277836

RESUMEN

Respiratory failure in COVID-19 is a common feature in fatal cases and has been considered as a failure of the immune system to control the virus. Here we report the case of COVID-19 affecting an immunocompromised women and her presumably immunocompetent spouse. A married couple (age 60 years) was simultaneously admitted to the emergency department on 10 March 2020 because of dyspnoea and fever, consistent with COVID-19. The wife (patient 1) was partially immunocompromised as a consequence of a recently started chemotherapy with fulvestrant and abemaciclid for recurring breast cancer, her husband (patient 2) had been healthy except for a history of controlled arterial hypertension. Both patients were treated with darunavir/cobicistat and hydroxychloroquine. The clinical course of the immunocompromised partner was benign, without need of intensive care. She was able to leave the hospital on day 6 after admission. In contrast, her husband needed intensive care and his recovery was slow, although eventually successful too. These findings suggest that the course of COVID-19 is not necessarily ominous in the presence of a compromised immune response and tend to reinforce the emerging therapeutic concepts of a controlled mitigation of the immune cascade following SARS CoV-2 infection.


Asunto(s)
Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Neoplasias de la Mama/complicaciones , Cobicistat/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Darunavir/uso terapéutico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Infecciones por Coronavirus/virología , Cuidados Críticos , Disnea/etiología , Servicio de Urgencia en Hospital , Femenino , Fiebre/etiología , Humanos , Inmunocompetencia , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pandemias , Neumonía Viral/virología , Esposos , Resultado del Tratamiento
2.
Anticancer Res ; 40(4): 2079-2087, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234900

RESUMEN

BACKGROUND/AIM: The European MRI and Rectal Cancer Surgery (EuMaRCS) score was proposed to identify preoperatively difficult laparoscopic total mesorectal excision (L-TME) for locally advanced rectal cancer (LARC). This study aimed to test EuMaRCS's validity. PATIENTS AND METHODS: Data were retrieved from a European multicenter database, including patients with mid/low LARC, treated with neoadjuvant chemoradiation therapy and L-TME with primary anastomosis. The EuMaRCS score was calculated on: BMI>30 (3 points), interspinous distance<96.4 mm (2 points), ymrT stage≥T3b (4 points), and male sex (1 point). RESULTS: The sample was composed of 141 patients, of whom 23 (16.3%) had a difficult L-TME. The EuMaRCS score demonstrated high accuracy in predicting difficult surgery (AROC: 0.806, 95%CI=0.72-0.88), with a cut-off >3 being associated with the best balance in sensitivity (82.6%) and specificity (66.1%). CONCLUSION: The EuMaRCS score represents a validated tool to predict preoperatively difficult L-TME in LARC patients.


Asunto(s)
Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/cirugía , Recto/cirugía , Cirugía Asistida por Computador/métodos , Anciano , Quimioradioterapia , Femenino , Humanos , Laparoscopía/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Recto/diagnóstico por imagen , Análisis de Supervivencia
3.
J Cancer Res Clin Oncol ; 146(5): 1335-1341, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32144536

RESUMEN

BACKGROUND/OBJECTIVE: Elderly patients with cancer are often at risk for undertreatment because of frailty, an aging-specific problem. However, current real-world conditions of recurrent ovarian cancer treatment in elderly patients remain unclear. This study aimed to clarify treatment patterns in elderly patients with recurrent ovarian cancer. PATIENTS AND METHODS: We used an ovarian cancer database containing the diagnosis and initial therapy of all patients at the National Cancer Center Hospital in Japan from 2007 to 2014. Patients were stratified into the platinum-sensitive group and the platinum-resistant group. We retrospectively assessed chemotherapy use in patients aged ≤ 64, 65-69, 70-74, 75-79, and ≥ 80 years. RESULTS: Among 253 patients (sensitive group: 135; resistant group: 118), by age group 91%, 95%, 100%, 100%, and 100% received chemotherapy in the sensitive group, and 79%, 67%, 50%, 29%, 0% received chemotherapy in the resistant group, respectively. In the resistant group, the percentage of patients aged 70-74 or 75-79 years who received chemotherapy was significantly lower than the percentage among patients aged ≤ 64 years, respectively (p = 0.01, p = 0.01). In multivariate analysis, age ≥ 70 years (odds ratio [OR], 4.412; 95% confidence interval (CI), 1.628-11.959; p = 0.004) and platinum-free interval < 3 months (OR, 3.434; 95% CI, 1.401-8.399; p = 0.007) were inversely associated with chemotherapy use. CONCLUSIONS: Doctors and patients did not consider chemotherapy in patients aged ≥ 70 years with platinum-resistant disease. Older age was independently and inversely associated with chemotherapy use in platinum-resistant ovarian cancer. Our results highlight the importance of demographic information in clinical decision-making for elderly patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carboplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos , Medicina Basada en la Evidencia , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/farmacología , Paclitaxel/administración & dosificación , Tasa de Supervivencia
4.
Tumori ; 106(2): 165-171, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32167020

RESUMEN

INTRODUCTION: In a gastric cancer (GC) setting, phase II and III studies refer to an ideal patient population and only describe a specific category of patients. Older patients or those in poorer clinical condition are generally excluded from clinical trials. We aimed to evaluate therapeutic approaches to GC in a real-world setting at our institute (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori [IRST] IRCCS) over a 10-year period. METHODS: A total of 621 consecutive patients with GC diagnosed between January 2000 and December 2009 were considered retrospectively. Among these, 573 with available information on stage of disease were included in the analysis. Demographic and clinical data were collected from paper or electronic medical records. RESULTS: During the study period, 343 (59.8%) patients were diagnosed with GC stage 0 to IIIC (M0): of these, 118 patients had a relapse of disease. A total of 230 patients (40.2%) presented with metastatic disease at diagnosis. Older age was associated with less frequent administration of adjuvant chemotherapy (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.83-0.91); interaction between age and period (OR, 1.02; 95% CI, 1.01-1.03) and stage of disease at diagnosis (OR, 7.95; 95% CI, 3.71-17.1) were positively associated with administration of adjuvant chemotherapy. Older age (OR, 0.87; 95% CI, 0.84-0.90) and presence of comorbidity (OR, 0.46; 95% CI, 0.26-0.83) were associated with less frequent administration of palliative chemotherapy, whereas from 2000-2004 to 2005-2009, patients were more frequently treated with palliative chemotherapy overall (OR, 3.70; 95% CI, 2.01-6.81). CONCLUSIONS: Our results confirm that resection is the standard surgical approach to GC, and that chemotherapy is not widely used in adjuvant and metastatic settings. Older age and comorbidities are associated with nontreatment.


Asunto(s)
Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/patología , Resultado del Tratamiento
5.
Anticancer Res ; 40(3): 1543-1550, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32132055

RESUMEN

BACKGROUND/AIM: The aim of the study was to assess the outcome of advanced ovarian cancer patients who i) underwent primary surgery followed by carboplatin/paclitaxel-based chemotherapy with or without bevacizumab, ii) were in complete response after chemotherapy, iii) and subsequently recurred. PATIENTS AND METHODS: The hospital records of 138 complete responders after chemotherapy with (n=58) or without (n=80) bevacizumab were reviewed. RESULTS: Both survival after recurrence and overall survival were related to age (≤61 vs. >61 years, p=0.002 and p=0.0001), performance status (0 vs. ≥1, p=0.002 and p=0.001), histotype (serous vs. non serous, p=0.005 and p=0.01), time to recurrence (≥12 vs. <12 months, p<0.0001 and p<0.0001) and treatment at recurrence (surgery plus chemotherapy vs. chemotherapy, p=0.01 and p=0.004), but not to first-line treatment. CONCLUSION: This investigation failed to detect a more aggressive behavior of recurrent ovarian cancer after bevacizumab-containing primary treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Bevacizumab/administración & dosificación , Carboplatino , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/patología , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
6.
Cancer Sci ; 111(4): 1324-1332, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32012411

RESUMEN

Interim results from the two-cohort, phase 2 KEYNOTE-100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4-11.2). We present outcomes for the Japanese patients (n = 21) enrolled in KEYNOTE-100. Patients with epithelial ROC had received either 1-3 prior chemotherapy lines and had platinum-free interval or treatment-free interval (PFI; TFI) of 3-12 months (cohort A) or 4-6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and higher programmed death ligand-1 (PD-L1) tumor expression. The relationship between PD-L1 expression (measured as combined positive score [CPS]) and ORR was assessed. Twenty-one Japanese patients (cohort A, n = 19; cohort B, n = 2) were treated. The median (range) age was 57 (37-78) years; 19 (90.5%) patients had ECOG status of 0 and 16 (76.2%) patients had stage III-IV disease. ORR was 19.0% (95% CI, 5.4-41.9) and seemed to increase with increasing PD-L1 expression. A total of 13 (61.9%) patients had treatment-related adverse events (TRAE), and 5 (23.8%) had grade 3-4 TRAE. There were no treatment-related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD-L1 expression among some patients with higher ORR.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antígeno B7-H1/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Japón/epidemiología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología
7.
Cancer Sci ; 111(4): 1124-1131, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32058620

RESUMEN

The identification of useful biomarkers is an urgent issue in cancer treatment, particularly for immunotherapy, as only some patients experience benefits from this treatment. The early induction of the IgG response has been reported as a useful biomarker of favorable prognosis for cancer patients treated with a personalized peptide vaccination, but a portion of these patients (IgG nonresponders) fail to achieve an early induction of IgG response yet experience long-term survival. It is thus necessary to identify other biomarkers of favorable prognosis among these patients. Here we report the usefulness of classical T-cell markers (ie, the CD8 content and the CD4/CD8 ratio in peripheral blood) in IgG nonresponders among advanced or recurrent ovarian cancer patients treated with a personalized peptide vaccination. Among IgG nonresponders (n = 25), the overall survival (OS) of the increased-CD8 group (n = 7) was significantly longer than that of the decreased-CD8 group (n = 18; P = .018), and the OS of the patients with a decreased CD4/CD8 ratio (n = 10) was significantly longer than that of the patients with an increased ratio (n = 15; P = .0055). Thus, an increased content of CD8 and a decreased CD4/CD8 ratio are each favorable prognosis markers in IgG nonresponders treated with a personalized peptide vaccination.


Asunto(s)
Antígenos CD4/sangre , Antígenos CD8/sangre , Neoplasias Ováricas/tratamiento farmacológico , Vacunas de Subunidad/administración & dosificación , Adulto , Anciano , Biomarcadores de Tumor/sangre , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/sangre , Inmunoterapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/inmunología , Neoplasias Ováricas/sangre , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Medicina de Precisión , Pronóstico , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Vacunas de Subunidad/efectos adversos
9.
Anticancer Res ; 40(2): 873-880, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014931

RESUMEN

BACKGROUND/AIM: The acidic tumor microenvironment is associated both with the progression and drug resistance of cancer. We aimed to investigate the effects of alkalization therapy performed concurrently with chemotherapy on the survival of advanced pancreatic cancer patients (study registration: UMIN 000035659). PATIENTS AND METHODS: Twenty-eight patients with metastatic or recurrent pancreatic cancer were assessed in this study. Alkalization therapy consisted of an alkaline diet with supplementary oral sodium bicarbonate (3.0-5.0 g/day). RESULTS: The mean urine pH was significantly higher after the alkalization therapy (6.85±0.74 vs. 6.39±0.92; p<0.05). The median overall survival from the start of alkalization therapy of the patients with high urine pH (>7.0) was significantly longer than those with low urine pH (≤ 7.0) (16.1 vs. 4.7 months; p<0.05). CONCLUSION: An alkalization therapy may be associated with better outcomes in advanced pancreatic cancer patients treated with chemotherapy.


Asunto(s)
Recurrencia Local de Neoplasia/dietoterapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Pancreáticas/dietoterapia , Neoplasias Pancreáticas/tratamiento farmacológico , Bicarbonato de Sodio/administración & dosificación , Anciano , Anciano de 80 o más Años , Suplementos Dietéticos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/orina , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/orina , Estudios Retrospectivos
11.
J Surg Oncol ; 121(3): 447-455, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31919848

RESUMEN

BACKGROUND: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC). METHODS: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC. Log-rank, Kaplan-Meier, and inverse probability of treatment weighting were used to assess differences in disease-free and overall survival between groups stratified by AC vs. NAC and pCR vs. non-pCR. RESULTS: The majority received AC (n = 787 or 62.8%) while 467 (37.2%) patients received NAC. Median follow up for AC and NAC groups was 46 and 28 months, respectively. The crude disease-free survival and overall survival of our study cohort were 92.2% and 89.1% for AC, 89.1% and 82.2% for NAC pCR, and 68.1% and 60.0% for NAC non-pCR, respectively. For clinical stage ≥IIB patients, NAC conferred a positive but statistically nonsignificant treatment effect over AC in multivariate analysis. CONCLUSIONS: After adjusting for imbalances in our subgroups, we found that, regardless of the sequence of chemotherapy (AC vs. NAC), patients with early-stage HER2+ breast cancer had excellent outcomes.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante/mortalidad , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
12.
Hematol Oncol ; 38(2): 162-170, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31922287

RESUMEN

Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo-HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft-versus-host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo-HSCT and need to be selected based on adverse event profiles.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Lenalidomida/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Trasplante Homólogo
13.
Nat Commun ; 11(1): 74, 2020 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-31900393

RESUMEN

Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Quinasa de Linfoma Anaplásico/genética , Apoptosis/efectos de los fármacos , Carbazoles/administración & dosificación , Reordenamiento Génico/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piperidinas/administración & dosificación , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Quinasa de Linfoma Anaplásico/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/fisiopatología , Inhibidores de Proteínas Quinasas/administración & dosificación , Factores de Transcripción/genética
14.
World Neurosurg ; 133: e252-e258, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31505283

RESUMEN

BACKGROUND: Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. METHODS: Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5-29 Gy (2-5 fractions) with 62%-75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. RESULTS: From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6-22 cm3 (median 14 cm3, P = 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. CONCLUSIONS: FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/secundario , Carcinoma/secundario , Recurrencia Local de Neoplasia/cirugía , Radiocirugia/métodos , Terapia Recuperativa/métodos , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Carcinoma/cirugía , Terapia Combinada , Irradiación Craneana , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos
15.
Int J Radiat Oncol Biol Phys ; 106(2): 291-299, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31629838

RESUMEN

PURPOSE: We evaluated the use of high dose-rate-like stereotactic body radiation therapy (SBRT) retreatment for biopsy-proven local persistence in prostate postradiation therapy, evaluating efficacy and toxicity. METHODS AND MATERIALS: From 2009 to 2018, 50 patients with biopsy-proven recurrent prostate cancer >2 years after prior treatment were retreated with a high dose-rate-like dose of 3400 cGy over 5 fractions. Previous radiation therapy dose measured 75.6 Gy (64.8-81.0) and median salvage interval was 8.1 years (32-241 mo.). Eighty-three percent of patients had Gleason score 7 or higher disease at retreatment. Those with preexisting toxicity >grade 1 from their prior course were excluded. The planning target volume was comprised of the clinical target volume (prostate + any contiguous extension only) with no additional expansion. Toxicity assessment used CTCAE v.3.0 criteria. RESULTS: Median follow-up was 44 months (3-110). Median pre-SBRT salvage baseline prostate specific antigen (PSA) of 3.97 ng/mL decreased to 0.6 ng/mL and 0.16 ng/mL at 1 and 5 years in nonrelapsed patients, respectively. Actuarial 5-year biochemical disease-free survival (DFS) measured 60%, with corresponding 5-year actuarial local, distant, and salvage androgen deprivation therapy free rates of 94%, 89%, and 69%, respectively. Actuarial 5-year biochemical DFS measured 78% if PSA at salvage was <6.92 ng/mL versus 12% with ≥6.92 ng/mL (P = .0001). Toxicity was primarily in the GU domain, with an 8% 5-year actuarial rate of grade 3+, 3% when limited to salvage of "conventional external beam only" local relapse. No gastrointestinal (GI) toxicity >grade 1 occurred. Of the 30% sexually potent at the time of salvage, 82% subsequently lost potency. CONCLUSIONS: SBRT salvage of local prostate recurrence in previously irradiated patients appears clinically feasible in this challenging group. It demonstrates favorable PSA and DFS response, typically deferring the need for salvage androgen deprivation therapy or other treatment by over 5 years, with low GU and GI toxicity.


Asunto(s)
Recurrencia Local de Neoplasia/radioterapia , Neoplasias de la Próstata/radioterapia , Radiocirugia/métodos , Reirradiación/métodos , Terapia Recuperativa/métodos , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Biopsia , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Estudios de Seguimiento , Humanos , Calicreínas/sangre , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Erección Peniana/efectos de la radiación , Próstata , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Radiocirugia/efectos adversos , Reirradiación/efectos adversos , Terapia Recuperativa/efectos adversos , Factores de Tiempo
16.
Gynecol Oncol ; 156(1): 38-44, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31699415

RESUMEN

OBJECTIVES: Olaparib is approved as maintenance therapy in patients with BRCA mutated platinum sensitive (PS) recurrent ovarian cancer (OC) after response to last platinum based therapy. Few data are available regarding the use out of the registration trials and on response to further treatments after progression. MATERIALS AD METHODS: In this non interventional, retrospective study, patients treated with olaparib in 13 centers, according to the label, have been collected and analyzed. Primary objectives of the study are to describe effectiveness and safety of olaparib in a real world setting with a focus on post progression treatments and response. RESULTS: 234 patients were analyzed. All patients were BRCA mutated and most of them had germline mutations. Around 50% of the patients received olaparib after 3 or more lines of platinum based chemotherapy achieving a radiologic complete (CR) or partial response. 12.4% patients with stable disease were also included. Median PFS was 14.7 months (95% CI:12.6-18), with statistically longer PFS in patients with normal serum Ca125 at baseline, a CR after last platinum based therapy and that received olaparib after second platinum based therapy. Median OS was not reached. Most frequent G3-G4 toxicity was anaemia (6%) with dose discontinuation and dose reduction in 11 (4.7%) and 49 (20.9%) of cases, respectively. Among 66 patients receiving further treatment after olaparib progression and evaluable for response, ORR was 22.2, 11.1% and 9.5% in patients with Platinum Free interval (PFI) of more than 12 months, between 6 and 12 months and less than 6 months, respectively. CONCLUSIONS: Olaparib is effective and safe in real world setting. Data on post-progression treatments seem to suggest cross resistance with chemotherapy and need to be confirmed in larger studies because of the potential importance in clinical practice decisions.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Antineoplásicos/administración & dosificación , Femenino , Genes BRCA1 , Genes BRCA2 , Mutación de Línea Germinal , Humanos , Quimioterapia de Mantención , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Supervivencia sin Progresión , Estudios Retrospectivos
17.
Gynecol Oncol ; 156(1): 32-37, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31739991

RESUMEN

BACKGROUND: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. METHODS: In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. RESULTS: Fifty patients were enrolled. Median age was 60.5 years (range 28-82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67-42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. CONCLUSIONS: Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Everolimus/administración & dosificación , Everolimus/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Supervivencia sin Progresión
18.
J Cancer Res Clin Oncol ; 146(3): 659-670, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31754832

RESUMEN

BACKGROUND: The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status. METHODS: We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O6-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression. RESULTS: Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002). CONCLUSIONS: This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/genética , Metilación de ADN/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Glioblastoma/genética , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Supervivencia sin Progresión , Regiones Promotoras Genéticas/genética , Estudios Retrospectivos , Proteínas Supresoras de Tumor/genética , Adulto Joven
19.
Gynecol Oncol ; 156(1): 23-31, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31791552

RESUMEN

OBJECTIVE: This phase 1b/2 clinical trial (NCT01663857) evaluated the efficacy of ralimetinib in combination with gemcitabine (G) and carboplatin (C), followed by maintenance ralimetinib, for patients with recurrent platinum-sensitive epithelial ovarian cancer. METHODS: Phase 1b was to determine the recommended phase 2 dose (RP2D) of ralimetinib administered Q12H on Days 1-10 (q21d) in combination with G (1000 mg/m2, Days 3 and 10) and C (AUC 4, Day 3) for six cycles. In phase 2, patients were randomized double-blind 1:1 to ralimetinib (R)+GC or placebo (P)+GC, for six cycles, followed by ralimetinib 300 mg Q12H or placebo on Days 1-14, q28d. RESULTS: 118 patients received at least one dose of ralimetinib or placebo; eight in phase 1b and 110 in phase 2 (R+GC, N = 58; P+GC, N = 52). The RP2D for R+GC was 200 mg Q12H. The study met its primary objective of a statistically significant difference in PFS (median: R+GC, 10.3 mo vs. P+GC, 7.9 mo; hazard ratio [HR] = 0.773, P = 0.2464, against a two-sided false positive rate of 0.4). Secondary objectives were not statistically significant for median overall survival (R+GC, 29.2 mo vs. P+GC, 25.1 mo; HR = 0.827, P = 0.4686) or overall response rate (R+GC 46.6% vs. P+GC, 46.2%; P = 0.9667). The safety profile of R+GC therapy was mainly consistent with safety of the chemotherapy backbone alone. Grade 3/4 elevated alanine aminotransferase was more common in the ralimetinib arm. CONCLUSIONS: Addition of ralimetinib to GC resulted in a modest improvement in PFS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Método Doble Ciego , Femenino , Humanos , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Quimioterapia de Mantención , Persona de Mediana Edad , Supervivencia sin Progresión , Piridinas/administración & dosificación , Piridinas/efectos adversos , Adulto Joven , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores
20.
Gynecol Oncol ; 156(1): 45-53, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31836184

RESUMEN

BACKGROUND: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. METHODS: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. RESULTS: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0-1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7-7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. CONCLUSION: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3.


Asunto(s)
Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Compuestos Organoplatinos/administración & dosificación , Neoplasias Ováricas/sangre , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Calidad de Vida , Tasa de Supervivencia
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