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1.
Radiat Oncol ; 15(1): 72, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252781

RESUMO

BACKGROUND: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. METHODS: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. RESULTS: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. CONCLUSIONS: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.


Assuntos
Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos
2.
Cancer Sci ; 111(4): 1375-1384, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958182

RESUMO

BRCAness is considered a predictive biomarker to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors. However, recent trials showed that its predictive value was limited in triple-negative breast cancer (TNBC) treated with platinum. Moreover, tumors with mutations of DNA damage response (DDR) genes, such as homologous recombination (HR) genes, could be sensitive to platinum and PARP inhibitors. Thus, we aim to explore the relationship between mutation status of DDR genes and BRCAness in TNBC. We sequenced 56 DDR genes in 120 TNBC and identified BRCAness by array comparative genomic hybridization. The sequencing results showed that 13, 14, and 14 patients had BRCA, non-BRCA HR, and non-HR DDR gene mutations, respectively. Array comparative genomic hybridization revealed that BRCA-mutated and HR gene-mutated TNBC shared similar BRCAness features, both having higher numbers and longer length of large-scale structural aberration (LSA, >10 Mb) and similar altered chromosomal regions of LSA. These suggested non-BRCA HR gene-mutated TNBC shared similar characteristics with BRCA-mutated TNBC, indicating non-BRCA HR gene-mutated TNBC sensitive to platinum and PARP inhibitors. Among tumors with mutation of non-HR DDR genes, 3 PTEN and 1 MSH6 mutation also contained significant LSAs (BRCAness); however, they had different regions of genomic alteration to BRCA and HR gene-mutated tumors, might explain prior findings that PTEN- and MSH6-mutated cancer cells not sensitive to PARP inhibitors. Therefore, we hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors. Direct sequencing DDR genes in TNBC should be applied to predict their sensitivity toward platinum and PARP inhibitors.


Assuntos
Dano ao DNA/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Recombinação Homóloga/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteína BRCA1/genética , Proteína BRCA2/genética , Dano ao DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação/genética , Platina/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genética
3.
J Xray Sci Technol ; 28(1): 111-124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31904003

RESUMO

BACKGROUND: Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy. OBJECTIVE: To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy. METHODS: HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions). RESULTS: The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p < 0.001) and longer estimated treatment times (p < 0.001). CONCLUSIONS: VMAT and HT plans are suitable for EF BMS radiotherapy, which can achieve adequate target volume coverage while sufficiently sparing normal tissue. In addition, VMAT, compared to HT planning, yielded shorter estimated treatment times.

4.
J Formos Med Assoc ; 119(1 Pt 1): 97-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30852003

RESUMO

BACKGROUND: Heavily pretreated pancreatic cancer patients have a grave prognosis. In this case series study, we evaluated the safety and efficacy of nab-paclitaxel-based chemotherapy for such patients. METHODS: The data of pancreatic adenocarcinoma patients (n = 40) treated with nab-paclitaxel after the failure of gemcitabine or fluoropyrimidines at our institution in 2013-2015 were reviewed. RESULTS: The median number of prior chemotherapy regimens was two (range, 1-6). Eighteen patients had an Eastern Cooperative Oncology Group performance status of ≥2. The regimens comprised nab-paclitaxel combined with the following drugs: gemcitabine (n = 28), gemcitabine and fluoropyrimidine (n = 3), platinum and fluoropyrimidine (n = 4), fluoropyrimidine (n = 4), and irinotecan and fluoropyrimidine (n = 1). The median dose of nab-paclitaxel was 63 (range, 51-72) mg/m2/dose, with the schedule of D1/15, D1/8, and D1/8/15 followed in 23, 14, and 3 patients, respectively. The median overall survival was 5.1 (95% CI, 4.6-5.7) months. Among 32 evaluable patients, two partial responses and six stable diseases were observed. The median progression-free survival was 2.6 (95% CI, 1.9-3.2) months. Grade 3/4 leucopenia or neutropenia was observed in three and two patients, respectively. Grade 3/4 anemia was observed in four patients. Other significant (grade 3 or more) nonhematological toxicities were not frequent, except for sepsis/infection (n = 7). However, more severe anemia or sepsis/infection was significantly associated with disease control. CONCLUSION: In heavily pretreated pancreatic adenocarcinoma patients, low-dose nab-paclitaxel-based chemotherapy was fairly tolerable with modest efficacy.

7.
Cancers (Basel) ; 11(8)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430901

RESUMO

Our previous study demonstrated that administration of NVP-BEZ235 (BEZ235), a dual PI3K/mTOR inhibitor, before radiotherapy (RT) enhanced the radiotherapeutic effect in colorectal cancer (CRC) cells both in vitro and in vivo. Here, we evaluated whether maintenance BEZ235 treatment, after combinatorial BEZ235 + RT therapy, prolonged the antitumor effect in CRC. K-RAS mutant CRC cells (HCT116 and SW480), wild-type CRC cells (HT29), and HCT116 xenograft tumors were separated into the following six study groups: (1) untreated (control); (2) RT alone; (3) BEZ235 alone; (4) RT + BEZ235; (5) maintenance BEZ235 following RT + BEZ235 (RT + BEZ235 + mBEZ235); and (6) maintenance BEZ235 following BEZ235 (BEZ235 + mBEZ235). RT + BEZ235 + mBEZ235 treatment significantly inhibited cell viability and increased apoptosis in three CRC cell lines compared to the other five treatments in vitro. In the HCT116 xenograft tumor model, RT + BEZ235 + mBEZ235 treatment significantly reduced the tumor size when compared to the other five treatments. Furthermore, the expression of mTOR signaling molecules (p-rpS6 and p-eIF4E), DNA double-strand break (DSB) repair-related molecules (p-ATM and p-DNA-PKcs), and angiogenesis-related molecules (VEGF-A and HIF-1α) was significantly downregulated after RT + BEZ235 + mBEZ235 treatment both in vitro and in vivo when compared to the RT + BEZ235, RT, BEZ235, BEZ235 + mBEZ235, and control treatments. Cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), 53BP1, and γ-H2AX expression in the HCT116 xenograft tissue and three CRC cell lines were significantly upregulated after RT + BEZ235 + mBEZ235 treatment. Maintenance BEZ235 treatment in CRC cells prolonged the inhibition of cell viability, enhancement of apoptosis, attenuation of mTOR signaling, impairment of the DNA-DSB repair mechanism, and downregulation of angiogenesis that occurred due to concurrent BEZ235 and RT treatment.

8.
World J Gastrointest Oncol ; 11(8): 579-588, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31435460

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer mortality worldwide. The cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local treatment. Although radiotherapy has not been considered a preferred treatment modality for HCC, charged particle therapy (CPT), including proton beam therapy (PBT) and carbon ion radiotherapy (CIRT), possesses advantages (for example, it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation) and has emerged as an alternative treatment option for HCC. With the technological advancements in CPT, various radiation dosages of CPT have been used for HCC treatment via CPT. However, the efficacy and safety of the evolving dosages remain uncertain. To assess the association between locoregional control of HCC and the dose and regimen of CPT, we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical outcomes. Overall, CPT provides a better local control rate compared with photon beam therapy, ranging from 80% to 96%, and a 3-year overall survival ranging from 50% to 75%, and it results in rare grade 3 toxicities of the late gastrointestinal tract (including radiation-induced liver disease). Regarding CPT for the treatment of locoregional HCC, conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary tract. In contrast, the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.

9.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1694-1703, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31350264

RESUMO

BACKGROUND: Helicobacter pylori eradication has been shown to decrease gastric adenocarcinoma risk. The epidemiology of gastric lymphoma, which is also associated with H. pylori, and other rare subtypes of gastric cancer is less clear. This study comprehensively evaluated the incidence trend and the survival of gastric cancer in Taiwan by histologic subtype. METHODS: The incidence trends of gastric cancer in Taiwan from 1996 and 2013 were evaluated using data from the Taiwan Cancer Registry. The life-table method and the Cox proportional hazards analysis were used to evaluate the survival of gastric cancer. RESULTS: The incidence of all gastric cancers in Taiwan decreased from 15.97 per 100,000 in 1996 to 11.57 per 100,000 in 2013. The most frequent histologic subtype of gastric cancer in Taiwan was adenocarcinoma, followed by lymphoma and sarcoma (mainly gastrointestinal stromal tumor). The best survival was in patients with sarcoma, followed by lymphoma, neuroendocrine tumor, and adenocarcinoma. Generally, women had a better survival than men. The incidence of adenocarcinoma significantly decreased from 13.56 per 100,000 in 1996 to 9.82 per 100,000 in 2013 (P < 0.0001). In contrast, the incidences of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma did not decrease. CONCLUSIONS: The incidence of adenocarcinoma and lymphoma, both of which are associated with H. pylori, showed diverging trends. The survival of gastric cancer differed by histologic subtype and sex. IMPACT: The disparity in the incidence trends between gastric lymphoma and adenocarcinoma, both associated with H. pylori, warranted the need to search for additional risk factors of gastric lymphoma.

10.
J Clin Med ; 8(8)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357636

RESUMO

Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.

12.
Head Neck ; 41(9): 3201-3210, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31116482

RESUMO

BACKGROUND: We hypothesized that patients with head and neck squamous cell carcinoma (HNSCC) with smoking cessation during curative chemoradiotherapy (CRT) had fewer complications and lower tumor progression risks. METHODS: Sixty-three patients with nonmetastatic HNSCC who were smokers at diagnosis (carbon monoxide [CO] breath concentrations ≥3 ppm) and underwent curative CRT were prospectively enrolled. Successful smoking cessation throughout CRT was confirmed by CO breath concentrations <3 ppm at CRT completion. RESULTS: Forty-one patients (65%) successfully discontinued smoking throughout CRT. With a median 33-month follow-up, patients with successful smoking cessation during CRT had significantly fewer, greater, and lower probabilities of grade ≥3 acute toxicities (P = .01), progression-free survival (P = .03), and permanent gastrostomy or tracheostomy (P = .04), respectively, than those continuing smoking throughout CRT. In multivariate analysis, successful smoking cessation during CRT significantly reduced tumor progression risks (hazard ratio: 0.4, P = .05). CONCLUSION: Smoking cessation during curative CRT reduced treatment-related toxicities and tumor progression risks in patients with HNSCC.

13.
Anticancer Res ; 39(4): 2207-2215, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952769

RESUMO

BACKGROUND/AIM: The local control and clinical outcome of pediatric patients with high-risk neuroblastoma treated with tomotherapy as part of a modern multimodality paradigm was assessed. PATIENTS AND METHODS: Twenty-four high-risk neuroblastoma patients who received radiotherapy (RT) to the primary site using helical tomotherapy (median 21.6 Gy) were included. Local failure (LF) was correlated with biological and clinical prognostic factors. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. RESULTS: After a median follow-up of 43.5 months, the 3-year cumulative incidence of LF, EFS, and OS were 21.1%, 45.8%, and 62.9%, respectively. Elevated serum lactate dehydrogenase ≥1,500 U/l was associated with worse LF (p=0.02). There was no 3-year LF noted for patients with gross residual disease (GRD) who received more than 21.6 Gy. CONCLUSION: We demonstrated favorable local control of tomotherapy for the treatment of high-risk neuroblastoma. Dose escalation of RT for patients with GRD should be investigated.


Assuntos
Neuroblastoma/terapia , Radioterapia de Intensidade Modulada , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Neuroblastoma/sangue , Prognóstico , Risco , Resultado do Tratamento
14.
Cancers (Basel) ; 11(4)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999581

RESUMO

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of gastric lymphoma. Most gastric MALT lymphomas are characterized by their association with the Helicobacter pylori (HP) infection and are cured by first-line HP eradication therapy (HPE). Several studies have been conducted to investigate why most gastric MALT lymphomas remain localized, are dependent on HP infection, and show HP-specific intratumoral T-cells (e.g., CD40-mediated signaling, T-helper-2 (Th2)-type cytokines, chemokines, costimulatory molecules, and FOXP3+ regulatory T-cells) and their communication with B-cells. Furthermore, the reason why the antigen stimuli of these intratumoral T-cells with tonic B-cell receptor signaling promote lymphomagenesis of gastric MALT lymphoma has also been investigated. In addition to the aforementioned mechanisms, it has been demonstrated that the translocated HP cytotoxin-associated gene A (CagA) can promote B-cell proliferation through the activation of Src homology-2 domain-containing phosphatase (SHP-2) phosphorylation-dependent signaling, extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), B-cell lymphoma (Bcl)-2, and Bcl-xL. Furthermore, the expression of CagA and these CagA-signaling molecules is closely associated with the HP-dependence of gastric MALT lymphomas (completely respond to first-line HPE). In this article, we summarize evidence of the classical theory of HP-reactive T-cells and the new paradigm of direct interaction between HP and B-cells that contributes to the HP-dependent lymphomagenesis of gastric MALT lymphomas. Although the role of first-line HPE in the treatment of HP-negative gastric MALT lymphoma remains uncertain, several case series suggest that a proportion of HP-negative gastric MALT lymphomas remains antibiotic-responsive and is cured by HPE. Considering the complicated interaction between microbiomes and the genome/epigenome, further studies on the precise mechanisms of HP- and other bacteria-directed lymphomagenesis in antibiotic-responsive gastric MALT lymphomas are warranted.

15.
Anticancer Res ; 39(3): 1355-1364, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842169

RESUMO

BACKGROUND: Adults with rhabdomyosarcoma (RMS) have a worse clinical outcome compared to pediatric cases. In the present study, the failure pattern and clinical outcome of adult patients with RMS who received multimodality treatment at our Institution was assessed. PATIENTS AND METHODS: Data were retrospectively recorded and analyzed from 20 adult patients, aged 19 years or more, who were treated for RMS at our Institution between 2004 and 2015. Disease-free (DFS) and overall (OS) survival after starting treatment were calculated using the Kaplan-Meier method. The relationship of these outcome measures with the following variables was then assessed: Primary site, tumor stage, lymph node involvement, histological subtype, radiotherapy (RT), and duration of chemotherapy. RESULTS: Sixteen patients had localized RMS, and four had metastatic disease. For the whole patient cohort, the 3-year DFS and OS rates were 20%, and 45%, respectively. Patients with alveolar histological subtype had a better 3-year OS than those with other subtypes (p=0.038). The median OS rates for those with localized and metastatic disease were 53.2 (95% confidence interval(CI)=14.7-91.8) months, and 21.7 (95% CI=0-45.7) months, respectively (p=0.047). In patients with localized RMS, those who received RT (n=13) had a better median DFS (24.6 versus 6.0 months, p=0.009) and OS (53.2 versus 11.4 months, p=0.009) than those who did not (n=3). For patients receiving RT, concurrent chemotherapy with vincristine and cyclophosphamide (n=11) was associated with better 3-year DFS (36.4% versus 0%, p<0.001) and OS (81.8% versus 0%, p<0.001) compared with RT alone (n=2). Administration of chemotherapy for more than 19 weeks significantly correlated with better 3-year DFS (44% versus 0%, p=0.001) and OS (53.3% versus 0%, p<0.001) in those with localized RMS. CONCLUSION: In addition to staging and histological subtype, our results indicate that concurrent chemoradiotherapy and longer duration of chemotherapy were associated with significantly improved DFS and OS in adult patients with localized RMS.


Assuntos
Rabdomiossarcoma/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Rabdomiossarcoma/patologia , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
Strahlenther Onkol ; 195(8): 707-718, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30610356

RESUMO

PURPOSE: We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance-positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT). METHODS: Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). RESULTS: Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8-32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans <254 (10-3 min-1; p = 0.015) correlated with poor survival after CRT. In multivariate analysis, baseline TLG >277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031). CONCLUSIONS: The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Aumento da Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
18.
Anticancer Res ; 38(8): 4805-4812, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30061252

RESUMO

BACKGROUND/AIM: Radiotherapy is not routinely used in metastatic pancreatic ductal adenocarcinoma (PDAC). We conducted a phase I study to investigate concurrent chemoradiotherapy (CCRT) followed by chemotherapy. MATERIALS AND METHODS: S-1 was administered at 50-70 mg/m2/day with radiotherapy in 2.5-3.6 Gy/day for 10-12 fractions. After CCRT, gemcitabine (1,000 mg/m2 on days 1 and 15) and S-1 (60-100 mg/day on days 1-7 and 15-21), were administered in a 4-week cycle. RESULTS: After enrolling 10 patients, the study was terminated due to slow recruitment. Dose-limiting toxicities and maximum tolerated doses were not identified. Most patients experienced mild toxicities, including nausea, vomiting, and anorexia. One patient developed grade 3 infection. One patient achieved partial remission, while the remaining nine patients had stable disease, with a local disease control rate of 100% after CCRT. CONCLUSION: A short-course CCRT followed by chemotherapy was potentially feasible in patients with metastatic PDAC.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia/métodos , Desoxicitidina/análogos & derivados , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antígeno CA-19-9/sangue , Quimiorradioterapia/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Ácido Oxônico/efeitos adversos , Tegafur/efeitos adversos , Resultado do Tratamento
19.
Radiat Oncol ; 13(1): 157, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30153850

RESUMO

BACKGROUND: Our aim was to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in operable tongue cancer patients. METHODS: The presence of CD3+, CD4+, CD8+, and forkhead box protein P3-positive (FOXP3+) TILs in tumor tissues obtained from 93 patients during surgery was examined using immunohistochemistry. RESULTS: The 3-year overall survival (OS) of patients with a low CD8/FOXP3 ratio was significantly lower than that of patients with a high CD8/FOXP3 ratio (63.8% vs. 87.3%, p = 0.001). Patients with high FOXP3 had a significantly lower 3-year regional recurrence-free survival (RRFS) than did patients with low FOXP3 (49.3% vs. 87.3%, univariate log rank p = 0.000). A low CD4/FOXP3 ratio (68.4% vs. 93.7%, univariate log rank p = 0.002) was significantly unfavorable prognostic factors for 3-year distant metastasis-free survival (DMFS). CONCLUSIONS: In addition to clinicopathological characteristics, TIL markers represent prognosticators for clinical outcomes.


Assuntos
Linfócitos do Interstício Tumoral , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgia , Complexo CD3 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Feminino , Fatores de Transcrição Forkhead , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/química , Linfócitos do Interstício Tumoral/patologia , Masculino , Recidiva Local de Neoplasia , Prognóstico , Taiwan , Neoplasias da Língua/mortalidade
20.
PLoS One ; 13(8): e0202224, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30096190

RESUMO

We evaluated the prognostic significance of immunologic inhibitory biomarkers in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma levels of soluble MHC class I polypeptide-related sequence A (sMICA) and transforming growth factor-ß1 (TGF-ß1) were measured before and 2 weeks after CRT. The median follow-up was 32.9 months (range: 12.4-40.6 months). The pre-treatment sMICA (p < 0.001) and TGF-ß1 (p < 0.001) levels were significantly increased in HNSCC patients, compared to healthy controls. In HNSCC patients, the median pre-CRT and post-CRT sMICA levels were 43.1 pg/mL and 65.3 pg/mL, respectively, while the median pre-CRT and post-CRT TGF-ß1 levels were 57.7 ng/mL and 36.0 ng/mL, respectively. After CRT, 19 patients (63.3%) exhibited persistently elevated sMICA, six patients (20.0%) exhibited persistently elevated TGF-ß1, and five patients (16.7%) exhibited persistently elevated sMICA and TGF-ß1. Patients with persistently elevated sMICA and TGF-ß1 after CRT experienced an earlier tumor progression (p = 0.030), and poor overall survival (p = 0.010). Our results suggest that HNSCC patients who exhibit persistently elevated sMICA and TGF-ß1 levels after CRT are at higher risk of tumor progression or death.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/terapia , Antígenos de Histocompatibilidade Classe I/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fator de Crescimento Transformador beta1/sangue , Adulto , Idoso , Biomarcadores Tumorais/imunologia , Quimiorradioterapia , Progressão da Doença , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Solubilidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue
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