RESUMO
Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C-CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC.
Assuntos
Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Masculino , Feminino , Japão/epidemiologia , Idoso , Pessoa de Meia-Idade , Adulto , Receptor ErbB-2/genética , Idoso de 80 Anos ou mais , Genômica/métodos , Inibidor p16 de Quinase Dependente de Ciclina/genética , Proteína Supressora de Tumor p53/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , Bases de Dados Genéticas , Carcinoma Ductal/genética , Carcinoma Ductal/patologia , Carcinoma Ductal/terapia , Proteínas Proto-Oncogênicas B-raf/genética , Adulto Jovem , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/terapiaRESUMO
BACKGROUND: Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce. METHODS: A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment. RESULTS: Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6 months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7 months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1 months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4 months, which was superior to the median OS of 6.0 months for patients who received the best supportive care (log-rank p = 0.10). CONCLUSION: This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Estudos Retrospectivos , Idoso , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Intervalo Livre de Progressão , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: It is unclear witch regimen is optimal as salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) monotherapy for recurrent or metastatic head and neck cancer (RM-HNC). METHODS: This study enrolled 109 patients. Overall survival (OS) and progression-free survival 2 (PFS2) were compared between patients stratified by SCT regimen. RESULTS: Of the 109 patients, 55 underwent SCT after the failure of ICI monotherapy. The OS of these 55 patients was longer than that of patients who did not undergo SCT. The OS and PFS2 were similar between patients treated with paclitaxel (PTX) and cetuximab (Cmab) combination and those treated with PTX monotherapy. The occurrence of irAEs did not impact PFS2 nor OS. CONCLUSIONS: SCT can improve the survival outcomes of patients with RM-HNC. In addition to PTX and Cmab, PTX monotherapy is also considered an effective SCT regimen. SCT is effective regardless of the presence or absence of irAEs.
Assuntos
Neoplasias de Cabeça e Pescoço , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Paclitaxel , Terapia de Salvação , Humanos , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Cetuximab/uso terapêutico , Intervalo Livre de ProgressãoRESUMO
Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC.
RESUMO
BACKGROUND: During the COVID-19 pandemic, pedicle flaps instead of free flap transfer were recommended for head and neck reconstruction to reduce infection risk. Boron neutron-capture therapy in Japan was clinically approved in 2020 as a salvage radiotherapy for recurrent head and neck cancer following chemoradiotherapy. The efficacy and safety of salvage surgery following boron neutron-capture therapy remain unclear. CASE REPORT: We describe a 57-year-old male with crT4aN0M0 oral cancer after three different forms of radiotherapy including boron neutron-capture therapy, treated by salvage partial maxillectomy with both buccal fat pad and nasoseptal flaps. His postsurgical course was successful, without tracheostomy, and he had no Clavien- Dindo grade 3 or 4 complications. The pathological diagnosis was T4a squamous cell carcinoma with a negative surgical margin. No recurrence or metastasis had occurred at 113 days postoperatively. No opioid consumption was needed postoperatively. CONCLUSION: Pathological negative margins were achieved in this case and there were no severe complications. Further accrual of cases salvage surgery following boron neutron-capture therapy is required to clarify treatment strategies for recurrent head and neck cancer.
Assuntos
COVID-19/epidemiologia , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Terapia por Captura de Nêutron de Boro , Humanos , Japão/epidemiologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Procedimentos Cirúrgicos Ortognáticos , SARS-CoV-2 , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Retalhos Cirúrgicos , Resultado do TratamentoRESUMO
Immune checkpoint inhibitors (ICIs) have become the standard treatment for recurrent or metastatic head and neck cancer (RM-HNC). However, many patients fail to benefit from the treatment. Previous studies have revealed that tumor burden predicts the efficacy of ICIs, but this association remains unclear for RM-HNC. We retrospectively analyzed 94 patients with RM-HNC treated with ICI monotherapy. We estimated the tumor burden using the baseline number of metastatic lesions (BNML) and the baseline sum of the longest diameters of the target lesions (BSLD), and evaluated the association between BNML, BSLD, and standardized uptake value (SUV) and clinical outcomes. The median progression-free survival (PFS) was 7.1 and 3.1 months in the low-BNML and high-BNML groups, respectively (p = 0.010). The median PFS was 9.1 and 3.5 months in the low-BSLD and high-BSLD groups, respectively (p = 0.004). Moreover, patients with high SUVmax levels had worse overall survival (OS) and PFS. BNML, BSLD, and SUVmax are useful prognostic factors in patients with RM-HNC treated with ICIs. Imaging examinations before ICI treatment are recommended to predict the efficacy of ICIs. If the tumor burden is high, cytotoxic anticancer agents may be administered concomitantly with or prior to ICI monotherapy.
Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Carga TumoralRESUMO
Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare disease with a poor prognosis. Because of its rarity, there is no established therapeutic regimen in unresectable cases. We report a case of PSCCT treated with weekly paclitaxel (wPTX) for more than 2 years. A 59-year-old woman presented to our hospital with a progressively enlarging neck mass. CT and MRI scans showed a tumor arising from the right lobe of the thyroid, invading the esophagus and trachea, as well as partially surrounding and invading the right common carotid artery. It was deemed unresectable. Biopsy revealed poorly differentiated squamous cell carcinoma. wPTX therapy was initiated. The patient achieved a partial response and is still undergoing treatment 28 months later. Adverse events included grade 3 neutropenia and grade 2 peripheral sensory neuropathy, which were manageable. Long-term wPTX therapy has been effective in this case of unresectable PSCCT.
Assuntos
Carcinoma de Células Escamosas , Neoplasias da Glândula Tireoide , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Pré-Escolar , Feminino , Humanos , Paclitaxel , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: During the coronavirus disease 2019 (COVID19) pandemic, pedicle flaps (instead of free flaps) were recommended for reconstruction following wide resection for patients with head and neck cancer, in order to reduce the use of medical resources. Currently, there are no established treatment guidelines for patients with head and neck cancer with synchronous esophageal cancer. CASE REPORT: We present a 68-year-old male with cT4aN2cM0 oral floor and synchronous cT1bN1M0 esophageal cancers who had defective reconstruction following oral tumor resection before esophagectomy during the pandemic. At the initial surgery, the oral resected defect was reconstructed using supraclavicular artery flap. The subsequent esophagectomy was reconstructed by gastric tube reconstruction. Both postoperative courses were successful, without the need for postoperative ventilator use. The days from initial or second surgery to discharge were 14 or 16 days, respectively. CONCLUSION: This case had achieved negative surgical margins and recovered oral intake with tracheostomy decannulation. Further case accruement using supraclavicular artery flap is required for patients with head and neck cancer and synchronous esophageal cancer.
Assuntos
COVID-19 , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Idoso , Artérias , Esofagectomia , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMO
Although several prognostic factors in nivolumab therapy have been reported in recurrent or metastatic head and neck cancer (RM-HNC) patients, these factors remain controversial. Here, we conducted a multicenter retrospective cohort study to investigate the impact of clinico-hematological factors on survival in RM-HNC patients treated with nivolumab. We reviewed 126 RM-HNC patients from seven institutes. We evaluated the prognostic effects of clinico-hematological factors on survival. The median overall survival (OS) was 12.3 months, and the 1 year-OS rate was 51.2%. Patients without immune-related adverse events, lower relative eosinophil count, worse best overall response, higher performance status, and higher modified Glasgow Prognostic Score had worse survival. The score, generated by combining these factors, was associated with survival. Patients with score of 4-5 had worse survival than those with score of 2-3 and 0-1 [adjusted HR for PFS: score of 4-5, 7.77 (3.98-15.15); score of 2-3, 3.44 (1.95-6.06), compared to score of 0-1], [adjusted HR for OS: score of 4-5, 14.66 (4.28-50.22); score of 2-3, 7.63 (2.29-25.37), compared to score of 0-1]. Our novel prognostic score utilizing clinico-hematological factors might be useful to establish an individual treatment strategy in RM-HNC patients treated with nivolumab therapy.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab's efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.