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A 21 year-old Japanese man had a rapidly growing pedunculated soft tumor in the abdomen within the past year, the base of which had persisted for 17 years. A skin biopsy of the soft part resembled neurofibroma. However, the excised specimen showed that the tumor base comprised spindle cells arranged in a storiform fashion and expanded around fat cells with a honeycomb infiltration. All areas of the tumor were positive for CD34 and negative for S-100. Finally, the tumor was diagnosed as a myxoid dermatofibrosarcoma protuberance arising from a conventional area. The pedunculated shape on the conventional part was unique. Myxoid dermatofibrosarcoma protuberances may pose a diagnostic challenge, particularly with a small biopsy. Thus, we should carefully consider dermatofibrosarcoma protuberances or other malignant mesenchymal tumors as a differential diagnosis in cases of low cellularity and abundant stromal tumors resembling neurofibromas.
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Background: The lung cancer biopsy specimens obtained by endobronchial ultrasound-guide sheath (EBUS-GS) trans lung biopsy occasionally do not contain cancer cells. It is a problem that there is a possibility that they may not contain cancer cells. Aim of the study: To investigate the proportion of biopsy specimens containing cancer cells in total biopsy specimens. Materials & methods: Patients with lung cancer diagnosed by EBUS-GS were selected. The primary end point was the proportion of specimens containing tumors in the total specimens obtained by EBUS-GS. Results: Twenty-six patients were investigated. The percentage of specimens containing cancer cells in the total specimens was 79.0%. Conclusion: The proportion of biopsy specimens containing cancer cell to all biopsy specimens by EBUS-GS was high, but not 100%.
The lung cancer biopsy specimens obtained by trans lung biopsy occasionally do not contain cancer cells. It is a problem that there is a possibility that they may not contain cancer cells. If the biopsy specimens contained no malignant cells, there was a possibility that accurate genetic test would not be performed and as a result, the correct molecular targeted drug would not be used. It is important to investigate the proportion of biopsy specimens containing cancer cells in total biopsy specimens. In this study, we showed the percentage of specimens containing cancer cells in the total specimens was 79.0%. This result should be considered to perform genetic test from biopsy specimens.
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BACKGROUND: Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC. METHODS: Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2 /day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2 /day. RD and MTD will be determined by evaluating toxicities. DISCUSSION: Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD-SCLC.
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Quimiorradioterapia , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Adulto , Idoso , Antraciclinas , Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Etoposídeo , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto JovemRESUMO
Pulmonary sarcomatoid carcinoma (SC) is an aggressive subtype of lung cancer that exhibits resistance to cytotoxic chemotherapy. Although programmed cell death 1 (PD-1) inhibitors have been reported to show antitumor effects in patients with high programmed death-ligand 1 (PD-L1) expressing SC, the efficacy of combined therapy with PD-1 inhibitor plus cytotoxic chemotherapy has not previously been clarified. We herein report a case of SC with low expression of PD-L1 and few pre-existing tumor-infiltrating lymphocytes which showed a remarkable response to pembrolizumab plus cytotoxic chemotherapy as first-line treatment. Our findings suggest that combined treatment might enhance the immunogenic response, even in immunologically ignored SCs.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Platina/uso terapêutico , Sarcoma/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Humanos , Masculino , Platina/farmacologiaRESUMO
BACKGROUND: S-1 and pemetrexed (PEM) are key treatments for non-small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S-1 and PEM is similar. Cross-resistance between S-1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. METHODS: This retrospective study included patients with advanced (c-stage III or IV, UICC seventh edition) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%-10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively. CONCLUSIONS: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with nonsquamous (non-SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Pemetrexede/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Dabrafenib and trametinib therapy for BRAF V600E-mutant non-small cell lung cancer (NSCLC) has demonstrated strong antitumor effects in clinical trials and has been approved for use in clinical practice. However, the efficacy and safety of this combination therapy in elderly patients remain unclear. An 86-year-old male patient, who had been diagnosed with lung adenocarcinoma with the BRAF V600E mutation, received dabrafenib and trametinib combination chemotherapy. The tumor shrunk rapidly; however, therapy was discontinued after 40 days because adverse events (hypoalbuminemia, peripheral edema, and pneumonia) developed. Although this targeted combination therapy seemed to cause relatively severe adverse events compared with single-agent targeted therapy in this "oldest old" elderly patient, the marked tumor shrinkage prolonged the patient's life and helped him to maintain a good general condition. Active targeted therapy may therefore be considered with appropriate drug dose reduction instead of conservative treatment, even if a patient is extremely old.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/metabolismo , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Imidazóis/farmacologia , Neoplasias Pulmonares/patologia , Masculino , Mutação , Oximas/farmacologia , Piridonas/farmacologia , Pirimidinonas/farmacologiaRESUMO
BACKGROUND: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression. PURPOSE: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. PATIENTS AND METHODS: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. RESULTS: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32-86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). CONCLUSIONS: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy.
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Fabry disease is an X-linked recessive inborn metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (EC 3.2.1.22). The causative mutations are diverse, include both large rearrangements and single-base substitutions, and are dispersed throughout the 7 exons of the alpha-galactosidase A gene (GLA). Mutation hotspots for Fabry disease do not exist. We examined 62 Fabry patients in Japan and found 24 GLA mutations, including 11 novel ones. A potential treatment reported for Fabry disease is active site specific chaperone (ASSC) therapy using 1-deoxygalactonojirimycin (DGJ), an inhibitor of alpha-galactosidase A, at subinhibitory concentrations. We transfected COS-7 cells with the 24 mutant GLAs and analyzed the alpha-galactosidase A activities. We then treated the transfected COS-7 cells with DGJ and analyzed its effect on the mutant enzyme activities. The activity of 11 missense mutants increased significantly with DGJ. Although ASSC therapy is useful only for misfolding mutants and therefore not applicable to all cases, it may be useful for treating many Japanese patients with Fabry disease.
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Povo Asiático/genética , Doença de Fabry/enzimologia , Doença de Fabry/genética , Chaperonas Moleculares/metabolismo , Mutação/genética , alfa-Galactosidase/genética , Adolescente , Adulto , Animais , Sítios de Ligação , Células COS , Criança , Chlorocebus aethiops , Humanos , Japão , Pessoa de Meia-IdadeAssuntos
Hemangioma , Dermatopatias Vasculares , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Humanos , Glândulas Écrinas/patologia , Proteínas WT1 , Hemangioma/patologia , Neoplasias Cutâneas/patologia , Dermatopatias Vasculares/patologia , Proliferação de Células , Neoplasias das Glândulas Sudoríparas/patologiaRESUMO
The circulating tumor DNA (ctDNA) assay has recently been approved for the selection of EGFR-tyrosine kinase inhibitors as first-line treatment in lung cancer. However, it remains to be determined whether this assay can detect all complex EGFR mutations within a single tumor. We report a case of an elderly woman with stage IV lung adenocarcinoma, in which EGFR mutation assays detected L858R and pretreatment T790M from a tissue biopsy. In contrast, the circulating tumor DNA assay detected L858R, but not pretreatment T790M in the plasma, regardless of the fact that similar amounts of each mutation were present in the biopsy specimen. Treatment with afatinib was not effective, but subsequent treatment with osimertinib remarkably regressed the tumor. Our findings indicate that physicians should accurately evaluate EGFR-tyrosine kinase inhibitor-insensitive mutations using tissue samples in the first-line setting, even when L858R and exon 19 deletions are detected in the plasma.
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Receptores ErbB/genética , Idoso , Feminino , Humanos , Neoplasias Pulmonares/genética , MutaçãoRESUMO
Promising outcomes of salvage chemotherapy after nivolumab therapy have been reported; however, little is known about the detailed clinical and immunologic features in lung cancer patients in whom nivolumab is unsuccessful. We report two cases of nivolumab-refractory lung cancer, in which chemotherapy resulted in rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens showed PD-ligand 1 (PD-L1)-expressing cancer cells, accompanied by tumor-infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive regulatory T cells and cells positive for TIM-3 were also observed. Physicians should take caution in treating lung cancer patients after progression on nivolumab. Further studies with a large cohort are warranted to identify the patients that may benefit from salvage chemotherapy.
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Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Salvação/métodos , Idoso , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , NivolumabeRESUMO
Pulmonary pleomorphic carcinoma has been shown to respond remarkably to PD-1 inhibitors; however, the biomarkers for this therapy have not been fully proven. We report a case of pulmonary pleomorphic carcinoma with overexpressed PD-L1, in which a complete response to nivolumab was sustained for >14 months. Immunohistochemical analysis revealed few PD-1+ immune cells and regulatory T cells in the tumor, in addition to predominant infiltration of CD8+ cells and macrophages. Our findings suggest that the presence of a small number of PD-1+ immune cells and regulatory T cells should be investigated as candidate therapeutic biomarkers.
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Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Idoso , Anticorpos Monoclonais/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , NivolumabeRESUMO
Little is known about the anti-tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD-L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre-existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients.