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1.
BMC Womens Health ; 23(1): 186, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081439

RESUMO

BACKGROUND: In Japan, 8000 women were newly diagnosed with cervical cancer in 2018. The healthcare insurance policy in Japan allows physicians to utilize vaginal volt cytology tests and serum biomarker measurement at every visit and imaging analysis at an adequate interval with screening for recurrence after initial treatment. However, the major surveillance guidelines published in the United States and European countries recommend focusing on pelvic examinations and symptom reviews to avoid unnecessary tests. This study aimed to reassess the benefits of standard surveillance methods adopted in this study by retrospective analysis. METHODS: From January 2009 to December 2015, the medical records of patients with recurrence who were initially diagnosed with International Federation of Gynecology and Obstetrics stage I-III cervical cancer were collected for this study. Clinicopathological data were statistically analyzed to identify significant factors. In the first 2 years, the patients underwent regular surveillance, including pelvic examination, serum tumor marker tests, vaginal vault cytology every 1-3 months, and imaging analysis at 6- to 12-month intervals. In the following 2 years, the patients received a regular check with the same methods every 4 months and an annual imaging analysis. Afterward, the patients had regular screening every 6 to 12 months. RESULTS: In the study period, 84 of the 981 patients experienced recurrence, and 88.1% had an asymptomatic recurrence. The disease-free interval was not related to the recurrence site. In univariate analysis, primary treatment, recurrence site, and diagnostic method were significant factors for survival outcomes. In contrast, multivariate analysis indicated that only primary treatment was a significant factor. In patients with local recurrence, multivariate analysis demonstrated that radiation as salvage therapy was an independent predictive factor for overall survival after recurrence. CONCLUSIONS: In this retrospective study, routine imaging analysis and serum biomarker measurement did not contribute to patient prognosis after recurrence. In contrast, vaginal vault cytology can improve survival after recurrence in some patients. Tailored surveillance methods based on individual disease conditions and treatment modalities can improve post-recurrent survival outcomes.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Citodiagnóstico , Vagina/patologia , Prognóstico , Recidiva Local de Neoplasia/patologia
2.
Jpn J Clin Oncol ; 52(8): 859-868, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35470390

RESUMO

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Feminino , Humanos , Estudos Prospectivos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia
3.
Gynecol Oncol ; 163(1): 105-109, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34294413

RESUMO

OBJECTIVE: The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity. METHODS: From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTVHR D90 were compared. RESULTS: Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50-60 Gy, 60-70 Gy, 70-80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. CONCLUSIONS: The low-risk patients achieved favorable local control with CTVHR D90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.


Assuntos
Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
4.
Int J Mol Sci ; 23(1)2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35008475

RESUMO

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature.


Assuntos
Mutação/genética , Tolerância a Radiação/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Análise Mutacional de DNA/métodos , Feminino , Humanos , Inflamação/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Smad4/genética
5.
Int J Clin Oncol ; 24(5): 575-582, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30580379

RESUMO

BACKGROUND: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. METHODS: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. RESULTS: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. CONCLUSIONS: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.


Assuntos
Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/radioterapia , Carcinoma Adenoescamoso/cirurgia , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia
6.
Int J Mol Sci ; 20(18)2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31540114

RESUMO

Radiotherapy is an essential component of cancer therapy. Carbon ion radiotherapy (CIRT) promises to improve outcomes compared with standard of care in many cancers. Nevertheless, clinicians often observe in-field recurrence after CIRT. This indicates the presence of a subset of cancers that harbor intrinsic resistance to CIRT. Thus, the development of methods to identify and sensitize CIRT-resistant cancers is needed. To address this issue, we analyzed a unique donor-matched pair of clinical specimens: a treatment-naïve tumor, and the tumor that recurred locally after CIRT in the same patient. Exon sequencing of 409 cancer-related genes identified enrichment of somatic mutations in FGFR3 and FGFR4 in the recurrent tumor compared with the treatment-naïve tumor, indicating a pivotal role for FGFR signaling in cancer cell survival through CIRT. Inhibition of FGFR using the clinically available pan-FGFR inhibitor LY2874455 sensitized multiple cancer cell lines to carbon ions at 3 Gy (RBE: relative biological effectiveness), the daily dose prescribed to the patient. The sensitizer enhancement ratio was 1.66 ± 0.17, 1.27 ± 0.09, and 1.20 ± 0.18 in A549, H1299, and H1703 cells, respectively. Our data indicate the potential usefulness of the analytical pipeline employed in this pilot study to identify targetable mutations associated with resistance to CIRT, and of LY21874455 as a sensitizer for CIRT-resistant cancers. The results warrant validation in larger cohorts.


Assuntos
Radioterapia com Íons Pesados , Recidiva Local de Neoplasia/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Células A549 , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Feminino , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Indazóis/farmacologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Projetos Piloto , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Transdução de Sinais , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/radioterapia
7.
Int J Hyperthermia ; 35(1): 226-231, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30221574

RESUMO

PURPOSE: This study aimed to elucidate the contribution of T cell-mediated antitumor immunity in the antitumor effect of local hyperthermia (LH). MATERIALS AND METHODS: C57BL/6J mice were injected with the mouse lymphoma cell line, E.G7-OVA, in the right femur on day 0. LH was induced by immersing the right femur in a water bath at 42 °C for 60 min on day 7, followed by administration of anti-CD8 monoclonal antibodies (mAb) or anti-CTLA-4 mAb (days 8, 11, and 14). The effect of LH on tumor growth (TG) was assessed by measuring the duration until tumor volume reached 1000 mm3 and survival time. Tumor-specific T cell responses were measured using enzyme-linked immunospot (ELISpot) assay. RESULTS: TG with and without LH treatment was 9.0 ± 9.6 and 7.0 ± 1.6 days, respectively. TG was significantly slower with LH treatment (p = .01). The therapeutic effect of LH was mitigated by addition of anti-CD8 mAb (p < .05 for both TG and survival) compared with the untreated (control) group. Furthermore, addition of anti-CTLA-4 mAb did not significantly affect the therapeutic effect of LH. The ELISpot assay showed that the number of spots in the LH group (276.3 ± 14.5) was significantly greater than in the control group (59.0 ± 4.5, p < .001). CONCLUSION: CD8-positive T cell-mediated antitumor immunity significantly contributes to the antitumor effect of LH.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Hipertermia Induzida/métodos , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/patologia
8.
BMC Cancer ; 16: 244, 2016 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-27008430

RESUMO

BACKGROUND: The prognostic value of rectal invasion is still unclear in stage IVA cervical cancer. The objective of this study is to evaluate patient outcome and prognostic factors in stage IVA cervical cancer treated with radiation therapy. METHODS: A retrospective review of the medical records of patients treated with definitive photon radiation therapy for pathologically proven stage IVA cervical cancer between 1980 and 2010 was performed. Eligible patients for the present study were diagnosed with clinical stage IVA cervical cancer by cystoscopy or/and proctoscopy, and they received definitive radiation therapy consisting of a combination of external beam radiotherapy and high-dose-rate brachytherapy. All patients underwent CT scans of the abdomen and pelvis. RESULTS: Among the 67 stage IVA patients studied, 53 patients were stage IVA on the basis of bladder invasion, 7 according to rectal mucosal invasion, and 7 because of both bladder and rectal mucosal invasion. Median follow-up of all patients and surviving patients was 19 months (range, 2-235 months) and 114 months (range, 14-223 months), respectively. The 5-year local control (LC), disease-free survival (DFS), and overall survival (OS) rate were 55, 17, and 24%, respectively. Rectal invasion had significant impact on DFS, but bladder invasion had the opposite effect (p = 0.00006 and 0.005, respectively). There were significant differences of LC, DFS and OS rates between patients with and without rectal invasion (p = 0.006, 0.00006 and 0.05, respectively). CONCLUSIONS: Patients with stage IVA cervical cancer had poor prognosis, with 5-year survival of only 24%. Furthermore, in stage IVA, rectal invasion might be a worse prognostic factor than bladder invasion.


Assuntos
Prognóstico , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Cistoscopia/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reto/patologia , Reto/cirurgia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias do Colo do Útero/patologia
9.
Cancer ; 120(11): 1663-9, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24591084

RESUMO

BACKGROUND: This study sought to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced adenocarcinoma of the uterine cervix in a phase 1/2 clinical trial. METHODS: The treatment consisted of whole-pelvic irradiation of 36.0 gray equivalents (GyE) in 12 fractions and local boost with dose escalation from 26.4 to 38.4 GyE in 8 fractions. The dose escalation was performed with careful observation of acute normal tissue responses. Total dose to the cervical tumor was 62.4 to 74.4 GyE in 20 fractions. RESULTS: Between April 1998 and February 2010, 58 patients were treated with C-ion RT in this clinical trial. The number of patients with stage IIB, IIIB, and IVA disease were 20, 35, and 3, respectively. Median tumor size was 5.5 cm (range, 3.0-11.8 cm). Twenty-seven patients had pelvic lymph node metastases. The median follow-up period was 38 months. All patients completed the treatment schedule. Grade 2 or higher late toxicity was found in 8 patients: 5 with bladder and 2 with small intestine grade 2 toxicities, and 1 patient had grade 4 rectal complication, which was surgically salvaged. The 5-year local control rate, local control rate including salvage surgery, and overall survival rate in all cases were 54.5%, 68.2%, and 38.1%, respectively. CONCLUSIONS: Dose escalation of C-ion RT for adenocarcinoma of the uterine cervix was accomplished without severe toxicities except in 1 case. Although the number of patients in this study was small, the results support continued investigation and analysis to confirm therapeutic efficacy.


Assuntos
Adenocarcinoma/radioterapia , Radioterapia com Íons Pesados , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Radioterapia com Íons Pesados/efeitos adversos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
10.
Gynecol Oncol ; 132(1): 87-92, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24183732

RESUMO

OBJECTIVE: The authors performed phase I/II clinical trial to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced squamous cell carcinoma of the uterine cervix. METHODS: Between April 2000 and January 2006, 22 patients for Protocol 9902 were treated with C-ion RT. The number of patients with stage IIB, IIIB, and IVA diseases was 1, 18, and 3, respectively. All patients had bulky tumors measuring 4.0-12.0 cm (median 6.2 cm). The whole pelvic dose was fixed at 39.0 GyE for 13 fractions, and additional 15.0 GyE for 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, a dose-escalation study was planned for 2 fractions to GTV. Total dose to the cervical tumor was 64.0-72.0 GyE for 20 fractions. RESULTS: All patients completed the scheduled therapy and no patient developed Grade 2 or higher acute toxicity. There was no Grade 3 or higher late complications at each dose. The 5-year overall survival rate and local control rate were 50.0% and 68.2%, respectively. Seven out of the 16 patients who received 64.0-68.0 GyE developed local recurrences, but all patients who received 72.0 GyE maintained local control. CONCLUSIONS: There were no severe acute or late complications in this trial. C-ion RT has the potential to improve the treatment for locally advanced bulky cervical cancer by applying a total dose of 72.0 GyE, with the results lending incentive to further investigations to confirm the therapeutic efficacy.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Radioterapia com Íons Pesados , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Radioterapia com Íons Pesados/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Fatores de Tempo , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
11.
Front Oncol ; 14: 1366777, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774419

RESUMO

Objective: To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and cumulative minimal dose to 90% of the high-risk clinical target volume (CTVHR D90) on combined EBRT and image-guided adaptive brachytherapy (IGABT) for cervical cancer. Methods: Consecutive patients who underwent definitive radiotherapy or concurrent chemoradiotherapy for cervical cancer at Gunma University Hospital between January 2010 and December 2019 were retrospectively reviewed. Tumor volume at diagnosis and reduction ratio were calculated using magnetic resonance imaging at diagnosis and before the first IGABT session. The cumulative dose of EBRT and IGABT was calculated as an equivalent dose in 2 Gy fractions (EQD2). Optimal cutoff values were determined according to a receiver operating characteristic curve. Treatment outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards regression. Results: A total of 254 patients were included in the analysis. The median follow-up for all patients was 57 (2-134) months. The 5-year overall survival (OS) was 81.9%, progression-free survival (PFS) was 71.3%, and local control (LC) was 94.5%. The patients were divided into four groups according to tumor volume at diagnosis and reduction ratio. The group with tumor volume at diagnosis ≥ 34.1 cm3 and reduction ratio < 68.8% showed significantly worse OS, PFS, and LC than the other three groups (All p < 0.05). In this group, the patients with a cumulative CTVHR D90 < 69.6 GyEQD2 showed significantly worse PFS and LC (p = 0.042 and p = 0.027, respectively). In the multivariate analysis of OS, adenocarcinoma/adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage III/IV, and a reduction ratio of < 68.8% were independent significant poor prognostic factors (p = 0.045, p = 0.009 and p = 0.001, respectively). In the univariate analysis of LC, a reduction ratio of < 68.8% was the only poor prognostic factor (p = 0.041). Conclusion: The patients with large and poorly responding tumors had significantly worse prognoses in terms of OS, PFS, and LC, suggesting that dose escalation should be considered for such tumors.

12.
J Med Case Rep ; 18(1): 228, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38720351

RESUMO

BACKGROUND: Mesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix. CASE PRESENTATION: We treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m2) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life. CONCLUSIONS: This is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease.


Assuntos
Adenocarcinoma , Braquiterapia , Radioterapia com Íons Pesados , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/patologia , Radioterapia com Íons Pesados/métodos , Braquiterapia/métodos , Resultado do Tratamento , Quimiorradioterapia/métodos
13.
Jpn J Radiol ; 42(7): 777-784, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38568430

RESUMO

OBJECTIVE: This study aimed to show the results of radical radiation therapy (RT) and concurrent chemoradiotherapy (CCRT) for vulvar cancer (VC) based on data from a Japanese nationwide survey. MATERIALS AND METHODS: We collected data from 108 institutions on cases of VC diagnosed between January 2001 and December 2010. Patients with histologically proven squamous cell carcinoma and adenocarcinoma with curative intent were selected, and 172 patients with VC were included in this study. The collected data were analyzed for overall survival (OS) using the Kaplan-Meier method. Univariate and multivariate analyses were performed to examine the prognostic factors for patients with VC. RESULTS: The median follow-up period was 16.8 (range; 3.2-154.8) months. Fifty-five patients received CCRT, and 117 patients received RT alone. The 2-year OS rates (95% confidence interval [CI]) for stages I, II, III, and IV were 77.9% (55.8-100.0), 71.9% (53.8-89.9), 55.4% (42.5-68.3), and 41.5% (27.3-55.7) respectively. Univariate analyses showed that the FIGO stage (p = 0.001), tumor diameter (p = 0.005), and lymph node (LN) status (p = 0.001) were associated with OS. The concurrent use of chemotherapy resulted in a significantly longer OS in Stage III (p = 0.013). Multivariate analysis showed that the hazard ratios (95% CI) for tumor diameter, positivity for LN metastasis, and RT alone (no concurrent chemotherapy) were 1.502 (1.116-2.021), 1.801 (1.287-2.521), and 1.936 (1.187-3.159), respectively. CONCLUSIONS: Our analysis revealed that CCRT should be recommended, especially for Stage III VC patients. Further studies are warranted to determine who benefits from CCRT, considering primary tumor size and LN status. The study was registered at the University Hospital Medical Information Network (protocol number: UMIN000017080) on April 8th, 2015.


Assuntos
Carcinoma de Células Escamosas , Quimiorradioterapia , Neoplasias Vulvares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , População do Leste Asiático , Seguimentos , Japão , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Vulvares/terapia
14.
Cancers (Basel) ; 15(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36831552

RESUMO

BACKGROUND: Tumor mutational burden (TMB) and stromal CD8-positive tumor-infiltrating lymphocytes (CD8+TILs) serve important roles in antitumor immune responses to radiotherapy. This study aimed to elucidate the association between TMB, CD8+TILs, and clinical factors in patients with cervical cancer treated with radiotherapy. METHODS: Patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy, and with available somatic mutation data and immunohistochemical staining data from identical tumor tissues, were enrolled retrospectively. The association between TMB and/or CD8+TIL density and patient characteristics, mutation profiles, and treatment outcome was analyzed. RESULTS: The study analyzed 44 patients (median follow-up period, 61 months). There was no significant correlation between TMB and CD8+TIL density, or between TMB or CD8+TIL density and patient characteristics. TMB-high or CD8+TIL density-low status was associated with worse overall survival and distant metastasis-free survival; the predictive value of these factors became greater when used in combination. TMB-high or CD8+TIL density-high status was associated with ARID1A mutations. CONCLUSIONS: These data indicate independence of TMB and CD8+TIL density and the involvement of ARID1A alterations in antitumor immune responses in patients with cervical cancers treated with radiotherapy, warranting further mechanistic research and prospective validation.

15.
Anticancer Res ; 43(5): 2077-2084, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37097697

RESUMO

BACKGROUND/AIM: Prognostic factors, including CD8-positive tumor-infiltrating lymphocytes (CD8+TILs), in definitive radiotherapy (RT) for squamous cell carcinoma (SqCC) of the uterine cervix need to be studied. This study aimed to explore these factors in a retrospective cohort. PATIENTS AND METHODS: Patients with SqCC who underwent definitive RT comprising external beam RT and intracavitary brachytherapy at our facility between April 2006 and November 2013 were evaluated. CD8 immunohistochemistry was performed in pre-treatment biopsy samples to analyze the prognostic significance of CD8+TILs in the tumor nest. Positive staining was defined as at least one CD8+ lymphocyte infiltrating the tumor area in the specimen. RESULTS: In total, 150 consecutive patients were included. Among them, 66 (43.7%) patients had International Federation of Gynecology and Obstetrics (FIGO, 2008 edition) stage IIIA or higher progressive disease. The median follow-up period was 61 months. In the entire cohort, the 5-year cumulative rates of overall survival (OS), progression-free survival (PFS), and pelvic recurrence-free rate (PRFR) were 75.6%, 69.6%, and 84.8%, respectively. Of the 150 patients, 120 (80.0%) patients were CD8+TIL positive. The independent favorable prognostic factors were FIGO stage I or II disease, administration of concurrent chemotherapy, and CD8+TILs for OS (p=0.028, 0.005, and 0.038, respectively); FIGO stage I or II disease and CD8+TILs for PFS (p=0.015 and <0.001, respectively); and CD8+TILs for PRFR (p=0.017). CONCLUSION: The presence of CD8+TILs in the tumor nest may be a favorable prognostic factor of survival after definitive RT in patients with SqCC of the uterine cervix.


Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Linfócitos T CD8-Positivos/patologia , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia
16.
J Gynecol Oncol ; 34(3): e24, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36603849

RESUMO

OBJECTIVE: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. METHODS: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. RESULTS: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. CONCLUSION: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Braquiterapia/métodos , Neoplasias do Colo do Útero/patologia , Dosagem Radioterapêutica , Estudos Prospectivos , Pelve/patologia
17.
J Clin Med ; 11(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35683490

RESUMO

Image-guided adaptive brachytherapy (IGABT) using intracavitary and interstitial (IC/IS) techniques plays a pivotal role in definitive radiotherapy for locally advanced cervical cancers. However, the training opportunities for interstitial needle application are limited, preventing this technique from becoming widespread. This study aimed to develop a training simulator for IC/IS brachytherapy. The simulator consists of a soft silicone tumor phantom and acrylic tube mimicking the vagina; it has high visibility because of translucent materials and is compatible with computed tomography (CT) and magnetic resonance imaging (MRI). A patient harboring a typical bulky and irregular-shaped cervical tumor was selected from 495 in-house IGABT-treated candidates, and a tumor phantom (68 × 49 × 45 mm) modeled on this patient was produced from three-dimensional real-scale measurements of the MRI-based high-risk clinical target volume at first brachytherapy. In trial use by two physicians with different levels of IGABT skills, a Fletcher-Suit Asian Pacific applicator, and a Venezia applicator with interstitial needles were nicely applied to the simulator, facilitating successful creation of CT-based treatment plans consistent with clinical practice. Thus, the training simulator can be useful for the training of IC/IS brachytherapy, and warrants further research employing a greater number of phantoms and practitioners to verify its educational value.

18.
Anticancer Res ; 42(7): 3341-3348, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35790266

RESUMO

BACKGROUND/AIM: This study aimed to elucidate the effect of radiotherapy on expression of immune response-related genes in cervical cancer tissues. MATERIALS AND METHODS: Tumor tissues were obtained from 16 patients with cervical cancer before initiation of radiotherapy and after treatment with 10 Gy X-rays, delivered in five fractions. Expression of 730 immune response-related genes was assessed using an nCounter PanCancer Immune Profiling Panel (NanoString Technologies. Seattle, WA, USA). RESULTS: Of the 730 genes examined, 41 showed significant changes (fold change of >1.5 or <0.66) in expression in post-radiotherapy samples (28 up-regulated and 13 down-regulated). Analysis of immune cell type-specific genes suggested predominant upregulation of those related to innate immunity postradiotherapy. Interestingly, cytotoxic T-lymphocyte-associated protein (CTLA4), a key negative regulator of T-cell activation, was marked down-regulated in 93.7% of patients, with an average fold-change of 2.0. CONCLUSION: To our knowledge, this study is the first to show down-regulation of CTLA4 in clinical cervical cancer tissues after treatment with radiotherapy.


Assuntos
Neoplasias do Colo do Útero , Antígeno CTLA-4/genética , Regulação para Baixo , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/radioterapia
19.
Jpn J Radiol ; 40(5): 534-541, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34860358

RESUMO

PURPOSE: Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. MATERIALS AND METHODS: TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. RESULTS: The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0-35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. CONCLUSION: These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias do Colo do Útero , Biomarcadores Tumorais , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/radioterapia
20.
J Radiat Res ; 63(2): 290-295, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35152292

RESUMO

We herein report a retrospective analysis of the efficacy of a combination therapy of pelvic irradiation that excluded the common iliac lymph nodes region and image-guided brachytherapy (IGBT) for non-bulky (≤4 cm) cervical cancer. Thirty-three patients with stage I-II cervical squamous cell carcinoma (≤4 cm) and without pelvic/para-aortic lymphadenopathy who were treated with definitive radiotherapy alone between February 2009 and September 2016 were included. The radiotherapy consisted of CT-based small-pelvis irradiation (whole pelvis minus common iliac lymph node area) of 20 Gy/10 fractions followed by pelvic irradiation with a midline block of 30 Gy/15 fractions and IGBT of 24 Gy/4 fractions (6 Gy/fraction for high-risk [HR] clinical target volume [CTV] D90%). In-room computed tomography (CT) imaging with applicator insertion was used for brachytherapy planning, with physical examinations and diagnostic magnetic resonance imaging (MRI) also being referred to for determination of HR CTV. Over a median follow-up of 60.5 months (range, 7-89), two patients developed distant recurrence and one developed local and distant recurrence. Two patients died from cervical cancer, one from hepatocellular carcinoma and one from non-cancerous disease. The 2/5-year local control (LC), progression-free survival (PFS) and overall survival (OS) rates were 100%/96.7%, 93.8%/90.6% and 93.9%/93.9%, respectively. No pelvic/para-aortic lymph node recurrence was observed. There were no late complications of grade 3 or higher in the small bowel, large bowel/rectum, or bladder. Our results suggest that a combination therapy of IGBT plus small-pelvis irradiation excluding common iliac lymph nodes provides reasonable clinical outcomes and can be a treatment option in non-bulky (≤4 cm) cervical squamous cell carcinoma.


Assuntos
Braquiterapia , Carcinoma de Células Escamosas , Radioterapia Guiada por Imagem , Neoplasias do Colo do Útero , Braquiterapia/métodos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Pelve/patologia , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
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