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1.
Oncologist ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979778

RESUMEN

BACKGROUND: Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0. RESULTS: Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively). CONCLUSION: The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC.

2.
Tuberk Toraks ; 72(2): 107-113, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38869202

RESUMEN

Introduction: In addition to the two common epidermal growth factor receptor (EGFR) mutations, there are many uncommon mutations. Due to the high number of uncommon types, as well as the rarity of patients, there is lack of information regarding patient demographics, especially age distribution and smoking status. Against this background, we conducted an analysis to clarify the background of patients with uncommon EGFR mutations, especially considering their age distribution and smoking status. Materials and Methods: We retrospectively reviewed the medical records of non-small cell lung cancer (NSCLC) patients diagnosed in a multicenter clinical practice from 2002 to 2023. Patients included all cases of non-advanced and advanced NSCLC with uncommon EGFR mutations. Result: Information on 158 patients with uncommon EGFR mutation was collected. Median age was 72 years, with the age distribution showing that most patients were in their 70s. There was a significant difference between the proportion of patients aged up to 59 years and the proportion aged 75 years or older. In 88 patients with a smoking habit history, a significant correlation was found between smoking index and age. Among non-smokers, there was a peak between ages 70 and 74, which was older than the peak among smokers. Conclusions: Even in elderly patients and NSCLC patients with a history of smoking, although it is unclear whether EGFR mutation is common or uncommon, EGFR gene testing should be performed considering the possibility of these patients being EGFR-positive.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Fumar , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Masculino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/epidemiología , Femenino , Anciano , Receptores ErbB/genética , Persona de Mediana Edad , Estudios Retrospectivos , Fumar/efectos adversos , Fumar/epidemiología , Anciano de 80 o más Años , Adulto , Factores de Edad , Distribución por Edad
3.
Cancers (Basel) ; 16(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38730700

RESUMEN

Human epidermal receptor (HER) 2-positive advanced gastric cancer is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. Although combination therapy with trastuzumab and chemotherapy provides meaningful survival benefit, clinical trials targeting HER2 have failed to demonstrate clinical benefits in first- or subsequent-line treatment. Trastuzumab deruxtecan, an antibody-drug conjugate, has shown positive results even in later-line treatment and has become new standard treatment. In first-line therapy, combination therapy with pembrolizumab and trastuzumab plus chemotherapy demonstrated a dramatic response rate. Therefore, the FDA rapidly approved it without waiting for the results of survival time. The emergence of combination therapy including immunotherapy with HER2-targeting agents and the development of HER2 targeting agents with or without immunotherapy have been advancing for treating HER2-positive gastric cancer. In this review, we will discuss the current status of treatment development and future perspectives for HER2-positive gastric cancer.

4.
Invest New Drugs ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809355

RESUMEN

The oral multikinase inhibitors sorafenib and lenvatinib are currently available as first-line treatment for patients with unresectable or metastatic thyroid cancer. However, treatment options for patients who are refractory to these multikinase inhibitors are limited. This study aimed to evaluate the safety and efficacy of rechallenged lenvatinib after failure of both lenvatinib and sorafenib in patients with metastatic thyroid cancer in the real-world clinical practice. We retrospectively reviewed the data of consecutive 16 patients with metastatic thyroid cancer who received lenvatinib as a rechallenge after failure of initial lenvatinib and sorafenib treatment at Shizuoka Cancer Center between 2016 and 2023. Of these, the initial lenvatinib was discontinued in 12 patients owing to progressive disease, in 3 patients owing to adverse events, and in 1 patient owing to both. The overall response rate was 6.7%, and disease control was achieved by rechallenge with lenvatinib in all patients with the target lesions. The median progression free survival after rechallenging with lenvatinib was 15.0 months. No new signs of toxicity were observed after rechallenging with lenvatinib. Our findings suggest that rechallenge with lenvatinib after failure of both lenvatinib and sorafenib showed manageable safety and modest efficacy in patients with metastatic thyroid cancer in clinical practice. The strategy of lenvatinib rechallenge may provide an alternative option for patients with no targetable driver genes or when selective kinase inhibitors are not indicated.

5.
Anticancer Res ; 44(4): 1751-1757, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38537995

RESUMEN

BACKGROUND/AIM: The median age of subjects in many clinical trials of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor conducted to date has been approximately 60 years. However, it is not uncommon to encounter EGFR gene-positive patients in their 70s or 80s. Based on information obtained from these clinical trials, EGFR gene-positive non-small cell lung cancer (NSCLC) patients are considered to be younger than EGFR-negative patients. In this study, we analyzed clinical data to identify whether this assumption is true. PATIENTS AND METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed in a multicenter clinical practice from 2009 to 2023. Patients included all cases of non-advanced and advanced NSCLC. RESULTS: Information on 2,540 patients, including 605 EGFR gene-positive patients, was collected. The median age of EGFR-positive and EGFR-negative patients was 72 years and 71 years, respectively, and there was no significant difference in the age of patients between these two groups (p=0.7887). The most common age in these two groups was 70 years. Among the EGFR gene subtypes, the frequency of exon 19 deletion decreased with age, whereas that of EGFR L858R increased. CONCLUSION: Patients in their 70s and 80s with non-small cell lung cancer were relatively frequently EGFR gene-positive. To avoid missing out on treatment opportunities, EGFR gene testing should also be performed on patients in this age group.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudios Retrospectivos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Receptores ErbB
6.
Clin Cancer Res ; 30(7): 1264-1272, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38295160

RESUMEN

PURPOSE: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin and has shown preliminary efficacy in the treatment of gastric cancer. Study 120, a phase Ib/II open-label study, assessed efficacy and safety of E7389-LF in combination with nivolumab, a programmed cell death (PD)-1 inhibitor. This report focuses on the gastric cancer cohort within the expansion phase. PATIENTS AND METHODS: Eligible patients had unresectable, measurable gastric cancer, progression following a platinum drug plus fluoropyrimidine (1L), and a taxane-containing regimen (2L). The primary objective of the expansion phase was objective response rate, secondary objectives included safety and PFS, and exploratory objectives included overall survival and biomarker evaluation. Patients received E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks, both as intravenous infusions. Tumor responses were assessed every 6 weeks by the investigators per RECIST v1.1. Plasma and tumor biomarkers were assessed. RESULTS: In the 31 patients who received E7389-LF in combination with nivolumab, the objective response rate was 25.8% [confidence interval (CI), 11.9-44.6]. The median progression-free survival was 2.69 months (95% CI, 1.91-2.99) and median overall survival was 7.85 months (95% CI, 4.47-not estimable). The most common treatment-related TEAE of any grade were neutropenia (77.4%), leukopenia (74.2%), and decreased appetite (51.6%). E7389-LF in combination with nivolumab significantly increased CD8-positive cells at C2D1 (P = 0.039), and six of seven vascular markers and four IFNγ-related markers showed increases from C1D1. CONCLUSIONS: Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with gastric cancer, and no new safety signals were observed, compared with either monotherapy.


Asunto(s)
Nivolumab , Policétidos Poliéteres , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Furanos/efectos adversos , Cetonas/efectos adversos , Moduladores de Tubulina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
7.
Exp Ther Med ; 27(2): 81, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38274345

RESUMEN

Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.

8.
Oncologist ; 29(3): e330-e336, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-37950903

RESUMEN

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab has shown clinical benefit for metastatic colorectal cancer (mCRC) refractory to standard therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable). METHODS: We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab. RESULTS: The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance status in 19 (20%) patients. FTD/TPI plus bevacizumab was administered as second-line treatment in 74 (80%) patients and as third- or fourth-line treatment in 19 (20%) patients. The objective response rate was 4.9% (95% confidence interval [CI], 1.4%-12.2%), and the disease control rate was 67.9% (95% CI, 56.6%-77.8%). With a median follow-up time of 21.6 months, median overall survival and progression-free survival were 18.6 months (95% CI, 12.1-23.2) and 6.3 months (95% CI, 5.0-8.3), respectively. Neutropenia of grade ≥3 developed in 50 (54%) patients, whereas 2 (2%) patients experienced febrile neutropenia, and no treatment-related death was observed. CONCLUSION: Our data show the potential efficacy and acceptable safety profile of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Pirrolidinas , Neoplasias del Recto , Timina , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Bevacizumab/efectos adversos , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Uracilo , Oxaliplatino/uso terapéutico , Trifluridina/efectos adversos , Irinotecán/uso terapéutico , Demencia Frontotemporal/inducido químicamente , Demencia Frontotemporal/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Combinación de Medicamentos
9.
Case Rep Oncol ; 16(1): 1267-1273, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37928864

RESUMEN

The administration of chemotherapy to cancer patients with organ dysfunction raises concerns regarding its safety. The safety profile of patients with organ dysfunction due to rare diseases treated with chemotherapy plus immune checkpoint inhibitor is limited. Fibrinogen storage disease (FSD) is a rare disease that causes liver dysfunction through endoplasmic reticulum stress response due to abnormal accumulation of fibrinogen in the endoplasmic reticulum of hepatocytes. Although chemotherapy plus nivolumab is recommended as a standard first-line treatment for patients with advanced gastric cancer (AGC), its safety profile for patients with FSD is rarely available. In this study, an 80-year-old male with gastric cancer with positive lavage cytology was scheduled to receive palliative chemotherapy. This case had liver dysfunction of unknown cause, and a liver biopsy was performed. Histopathological findings revealed a diagnosis of type II/III fibrinogen inclusion based on morphology and immunohistochemistry. Liver function was recovered by administering ursodeoxycholic acid. Therefore, the combination chemotherapy of S-1, oxaliplatin, with nivolumab as palliative chemotherapy was initiated. The case responded well to chemotherapy and achieved conversion surgery without worsening of liver function. We report a case of AGC with fibrinogen inclusion complication where chemotherapy was safely administered with a good outcome. The combination therapy of cytotoxic drugs and immune checkpoint inhibitors may be safely and effectively administered to such patients.

10.
Maedica (Bucur) ; 18(3): 523-527, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38023741

RESUMEN

Chest wall lipoma is a rare disease that might be asymptomatic and discovered incidentally. Chest wall lipomas are presumed to grow slowly, but no reports have evaluated the tumor volume doubling time (TVDT). The present study herein reports the case of a 35-year-old female patient with a relatively fast-growing chest wall lipoma. Lipomas have their characteristic shape and grow very slowly, so they are rarely completely resected, even though they are monitored and repeated imaging studies are performed. Homogeneous very low density, clear margins, and no invasion to the surrounding structure are characteristic finding on imaging, but some patients without these characteristics here have been reported here. As there has been no report of TVDT for chest wall lipoma, comparison was not possible, but TDVT for lipoma in this patient ranged from 235-412 days. Compared with reports that patients with non-small cell lung cancer showed TVDT of less than 450 days, TVDT in the patient described here did not appear to be slow. Accumulation of knowledge about this rare disease will help to elucidate it further.

11.
Maedica (Bucur) ; 18(3): 515-518, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38023743

RESUMEN

We describe herein two patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) who developed cancer-associated ischemic stroke (CAIS), infarction caused by thromboembolism in the central nervous system. Case 1 was a 63-year-old man with Exon 19 deletion type EGFR mutated lung adenocarcinoma presenting with CAIS. Case 2 was a 71-year-old woman with Exon 21 L858R type EGFR mutated lung adenocarcinoma who developed CAIS during chemotherapy after EGFR-tyrosine kinase inhibitor (TKI) resistance. Although there was no recurrence of CAIS in these patients, anticancer therapy could be hampered by the comorbidity of CAIS. This can develop anytime from before clinical manifestations of NSCLC to the next treatment after EGFR-TKI resistance. The development of CAIS should be noted in patients with EGFR mutated NSCLC, who have a promising long-term prognosis. Anticancer and anticoagulant therapies as well as rehabilitation are important for patients who develop CAIS. Establishment of measurement tests to detect CAIS before onset is desired.

12.
Surg Case Rep ; 9(1): 145, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37589759

RESUMEN

BACKGROUND: Small bowel cancer (SBC) is a rare malignancy that is often diagnosed at an advanced stage. Palliative chemotherapy is the standard treatment for patients with metastatic SBC. The relevant literature on conversion surgery in patients who have responded favorably to chemotherapy is limited. CASE PRESENTATION: A 64-year-old man was diagnosed with jejunal carcinoma with multiple peritoneal metastases. After implanting an expandable metallic stent at the primary site, the patient underwent 6 months of FOLFOX therapy, resulting in a clinical complete response. Chemotherapy was continued, and four years after the initiation of therapy, the patient showed no evidence of disease progression. Nevertheless, anemia of continuous minor hemorrhages from the stent site and general malaise of chemotherapy got progressively worse during treatment. After confirming negative ascites cytology and the absence of peritoneal metastasis via staging laparoscopy, the patient underwent partial jejunectomy. Pathologically, no residual tumor was detected in the resected specimen. The postoperative course was uneventful, and the patient remained free of recurrence for 30 months after surgery without chemotherapy. CONCLUSION: Although infrequent, conversion surgery may be a valid therapeutic option for selected cases of SBC with peritoneal metastasis.

13.
PLoS Genet ; 19(6): e1010801, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37390104

RESUMEN

Sex chromosomes have evolved repeatedly across the tree of life and often exhibit extreme size dimorphism due to genetic degeneration of the sex-limited chromosome (e.g. the W chromosome of some birds and Y chromosome of mammals). However, in some lineages, ancient sex-limited chromosomes have escaped degeneration. Here, we study the evolutionary maintenance of sex chromosomes in the ostrich (Struthio camelus), where the W remains 65% the size of the Z chromosome, despite being more than 100 million years old. Using genome-wide resequencing data, we show that the population scaled recombination rate of the pseudoautosomal region (PAR) is higher than similar sized autosomes and is correlated with pedigree-based recombination rate in the heterogametic females, but not homogametic males. Genetic variation within the sex-linked region (SLR) (π = 0.001) was significantly lower than in the PAR, consistent with recombination cessation. Conversely, genetic variation across the PAR (π = 0.0016) was similar to that of autosomes and dependent on local recombination rates, GC content and to a lesser extent, gene density. In particular, the region close to the SLR was as genetically diverse as autosomes, likely due to high recombination rates around the PAR boundary restricting genetic linkage with the SLR to only ~50Kb. The potential for alleles with antagonistic fitness effects in males and females to drive chromosome degeneration is therefore limited. While some regions of the PAR had divergent male-female allele frequencies, suggestive of sexually antagonistic alleles, coalescent simulations showed this was broadly consistent with neutral genetic processes. Our results indicate that the degeneration of the large and ancient sex chromosomes of the ostrich may have been slowed by high recombination in the female PAR, reducing the scope for the accumulation of sexually antagonistic variation to generate selection for recombination cessation.


Asunto(s)
Struthioniformes , Masculino , Animales , Femenino , Struthioniformes/genética , Evolución Molecular , Recombinación Genética , Cromosomas Sexuales/genética , Evolución Biológica , Mamíferos/genética
14.
Oncologist ; 28(11): e1108-e1113, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37284901

RESUMEN

BACKGROUND: In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure. METHODS: We included a dose escalation (3 + 3 design) and an expansion cohort. Patients were administered trifluridine/tipiracil (25-35 mg/m2 twice daily, days 1-5), irinotecan (150-180 mg/m2, day 1), and bevacizumab (5 mg/kg, day 1) every 2 weeks. The recommended phase II dose (RP2D) in the dose escalation cohort was administered to at least 15 patients in both cohorts combined. RESULTS: Twenty-eight patients were enrolled. Five dose-limiting toxicities were observed. RP2D was defined as trifluridine/tipiracil 35 mg/m2, irinotecan 150 mg/m2, and bevacizumab 5 mg/kg. Of 16 patients who received RP2D, 86% (14/16) experienced grade ≥3 neutropenia without febrile neutropenia. Dose reduction, delay, and discontinuation occurred in 94%, 94%, and 6% of patients, respectively. Three patients (19%) showed partial response and 5 had stable disease for >4 months, with a median progression-free and overall survival of 7.1 and 21.7 months, respectively. CONCLUSION: Biweekly trifluridine/tipiracil, irinotecan, and bevacizumab administration may have moderate antitumor activity with high risk of severe myelotoxicity in previously treated patients with metastatic colorectal cancer [UMIN Clinical Trials Registry (UMIN000019828) and Japan Registry of Clinical Trials (jRCTs041180028)].


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Bevacizumab/uso terapéutico , Irinotecán/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Uracilo , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Combinación de Medicamentos
15.
Cancer Chemother Pharmacol ; 91(6): 469-480, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37140602

RESUMEN

PURPOSE: This two-part, open-label, non-randomized dose-escalation study aimed to define the maximum tolerated dose (MTD) of BI 836880 (humanized bispecific nanobody® targeting vascular endothelial growth factor and angiopoietin-2) as monotherapy and in combination with ezabenlimab (programmed death protein-1 inhibitor) in Japanese patients with advanced and/or metastatic solid tumors. METHODS: In part 1, patients received an intravenous infusion of BI 836880 at 360 or 720 mg every 3 weeks (Q3W). In part 2, patients received BI 836880 at doses of 120, 360, or 720 mg in combination with ezabenlimab 240 mg Q3W. The primary endpoints were the MTD and the recommended phase II dose (RP2D) of BI 836880 as monotherapy and in combination with ezabenlimab, based on dose-limiting toxicities (DLTs) during the first cycle. RESULTS: Twenty-one patients were treated; nine in part 1 and 12 in part 2. No DLTs were reported in either part and the MTD was not reached. The RP2Ds were BI 836880 720 mg Q3W as monotherapy and BI 836880 720 mg plus ezabenlimab 240 mg Q3W. The most common adverse events were hypertension and proteinuria (33.3%) with BI 836880 monotherapy and diarrhea (41.7%) with the combination. Four patients (44.4%) in part 1 had stable disease as best overall tumor response. In part 2, two patients (16.7%) had confirmed partial responses and five had stable disease (41.7%). CONCLUSION: MTD was not reached. BI 836880 alone and in combination with ezabenlimab had a manageable safety profile with preliminary clinical activity in Japanese patients with advanced solid tumors. TRIAL REGISTRATION AND DATE: NCT03972150, registered on June 3, 2019.


Asunto(s)
Inhibidores de la Angiogénesis , Anticuerpos Monoclonales , Neoplasias , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Angiopoyetina 2/antagonistas & inhibidores , Anticuerpos Monoclonales/uso terapéutico , Muerte Celular , Pueblos del Este de Asia , Dosis Máxima Tolerada , Neoplasias/patología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
17.
BMC Cancer ; 23(1): 68, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670426

RESUMEN

BACKGROUND: Nanoliposomal irinotecan plus fluorouracil/leucovorin (5-FU/LV) is a standard second-line therapy for patients with pancreatic cancer. Identification of biomarkers is important to determine appropriate treatment strategies. We investigated the clinical practice outcomes and biomarkers associated with the nanoliposomal irinotecan plus 5-FU/LV regimen. METHODS: We retrospectively reviewed the data of patients treated with nanoliposomal irinotecan plus 5-FU/LV as a second or subsequent treatment after gemcitabine-based therapy between June 2020 and March 2021 at Shizuoka Cancer Center. RESULTS: We analyzed 55 consecutive patients who met the selection criteria. At a median of 9.4 months, median progression-free survival (PFS) and median overall survival (OS) were 2.3 and 6.6 months, respectively. Multivariate analysis showed that Glasgow prognostic score (GPS) was significantly associated with PFS (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.09-4.30; P = 0.028) and OS (0 vs. 1 or 2: HR 2.46; 95% CI 1.15-5.25; P = 0.029). The OS was significantly longer in patients with CA19-9 response than in those without CA19-9 response (12.6 vs. 5.6 months; HR 0.24; 95% CI 0.08-0.75; P = 0.014). CONCLUSIONS: Nanoliposomal irinotecan was efficacious and tolerable in clinical practice. GPS and CA19-9 response were good candidates as predictive biomarkers, whereas GPS was a good candidate prognostic biomarker for the nanoliposomal irinotecan plus 5-FU/LV regimen.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Fluorouracilo , Irinotecán , Leucovorina , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Camptotecina , Fluorouracilo/uso terapéutico , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Liposomas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Pancreáticas
18.
J Hum Genet ; 68(2): 81-86, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36482120

RESUMEN

In 2021, Japan's national health insurance made germline BRCA (g.BRCA) testing available to unresectable pancreatic cancer (PC) patients as a companion diagnostic (CD) of the PARP inhibitor. This study investigated the incidence of the g.BRCA variant (g.BRCAv.) and the status of the genetic medicine associated with its testing. A total of 110 PC patients underwent the testing, five of whom (4.5%) had a deleterious g.BRCA2v. (all truncations) but no g.BRCA1v. The turnaround time (TAT) to the doctors was 13 days, and to the patients, 17 days. A higher incidence of a BRCA-related family history and a shorter TAT were seen in the g.BRCAv. patients, but they were insignificant (p = 0.085 and p = 0.059, respectively). Genetic counseling was not performed for three g.BRCA2v. patients because two of them had no accessible relatives and one died of the cancer before the genetic report was completed. Two families underwent generic counseling and testing based on the patient's genetic data. g.BRCAv. is recognized in a small fraction of PC cases, and the following genetic counseling is done more for the relatives than for the patients. TAT was constant and did not affect much on the genetic counseling, but the earlier testing is expected for patients with a deadly cancer.


Asunto(s)
Neoplasias Ováricas , Neoplasias Pancreáticas , Humanos , Femenino , Pruebas Genéticas , Pueblos del Este de Asia , Asesoramiento Genético , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Mutación de Línea Germinal/genética , Neoplasias Ováricas/genética , Predisposición Genética a la Enfermedad , Proteína BRCA1/genética , Neoplasias Pancreáticas
19.
Echocardiography ; 39(11): 1457-1461, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36258638

RESUMEN

We present the case of a fetus with cardiac capillary hemangioma in the right atrial cavity. The tumor showed dramatic growth between the 28th and 32nd week of gestation and resulted in tachyarrhythmia. The patient was born at the 33 weeks of gestation weighing 2430 g via urgent cesarean section because the rapidly growing cardiac tumor caused incessant tachyarrhythmia, pericardial effusion, and fetal circulatory incompetence. Coronary angiography revealed that the right coronary artery drained into the tumor. Due to hemodynamic deterioration, the patient underwent subtotal resection of the tumor on the 2nd day after birth. Histopathological examination revealed an undifferentiated capillary hemangioma. The patient was discharged at the age of 86 days, as the tachyarrhythmia and hemodynamic incompetence had subsided; however, bradycardia and intermittent atrioventricular conduction disturbance gradually developed. Capillary hemangioma, a rare primary cardiac space-occupying tumor in children, can invade the conduction system.


Asunto(s)
Neoplasias Cardíacas , Hemangioma Capilar , Niño , Humanos , Embarazo , Femenino , Lactante , Cesárea , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Hemangioma Capilar/complicaciones , Hemangioma Capilar/diagnóstico por imagen , Hemangioma Capilar/cirugía , Taquicardia , Feto/patología
20.
BMC Cancer ; 22(1): 1101, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36303119

RESUMEN

BACKGROUND: Postoperative chemoradiotherapy (CRT) is a standard therapy for patients with high-risk factors for head and neck squamous cell carcinoma, including positive margin and extra-nodal extension (ENE). However, the prognostic impact of the number of pathological metastatic lymph nodes (pLNs) in hypopharyngeal carcinoma (HPC) is unclear. Thus, this study aimed to investigate postoperative prognostic factors for locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) with a focus on the number of pLNs. METHODS: We retrospectively analyzed medical records of 99 consecutive patients with LA-HPSCC who underwent total pharyngo-laryngo-esophagectomy (TPLE) and bilateral neck dissection (ND) between December 2002 and May 2019. RESULTS: The median follow-up time for all censored patients was 63.2 months. The median overall survival (OS) was 101.0 months (95% confidence interval [CI] 48.1-134.9). patients had pLNs ≥ 3. Forty-six (45.5%) patients were diagnosed with ENE. Twenty (20.2%) patients received postoperative CRT. The multivariate analysis revealed that pLNs ≥ 3 (median OS: 163.2 vs. 31.8 months, hazard ratio [HR] 2.39, 95% CI 1.16-4.94, p < 0.01) and ENE (median OS: 161.0 vs. 26.3 months, HR 4.60, 95% CI 2.26-9.36, p < 0.01) were significantly associated with poor prognosis and that postoperative CRT (HR 0.34, 95% CI 0.16-0.72, p < 0.01) was significantly associated with better prognosis. The cumulative incidence of distant metastasis was higher in patients with pLNs ≥ 3 than in those with pLNs < 3 (p < 0.01). CONCLUSION: pLNs ≥ 3 and ENE were significant poor prognostic factors for patients with LA-HPSCC who underwent TPLE and bilateral ND.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Hipofaríngeas , Humanos , Neoplasias Hipofaríngeas/cirugía , Neoplasias Hipofaríngeas/patología , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/patología , Estadificación de Neoplasias
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