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BACKGROUND: The proven efficacy of mTOR inhibitors (mTORIs), tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma (RCC) suggests that these agents should be investigated as adjuvant therapy with the aim of eliminating undetectable microscopic residual disease after curative resection. The aim of our study was to compare the efficacy of these treatments using an innovative method of reconstructing individual patient data. METHODS: Nine phase III trials describing adjuvant RCC treatments were selected. The IPDfromKM method was used to reconstruct individual patient data from Kaplan-Meier (KM) curves. The combination treatments were compared with the control arm (placebo) for disease-free survival (DFS). Multi-treatment KM curves were used to summarize the results. Standard statistical tests were performed. These included hazard ratio and likelihood ratio tests for heterogeneity. RESULTS: In the overall population, the study showed that two ICIs (nivolumab plus ipilimumab and pembrolizumab) and one TKI (sunitinib) were superior to the placebo, whereas both TKIs and mTORIs were inferior. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown. CONCLUSIONS: This novel approach to investigating survival has allowed us to conduct all indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted.
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BACKGROUND: Some studies show that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) may improve overall survival and is a possible curative treatment for selected colorectal cancer (CRC) patients with restricted peritoneal metastasis (PM). The value of HIPEC in preventing PM of CRC is still controversial. MATERIALS AND METHODS: In this retrospective propensity score matching (PSM) cohort study, all patients with cT4N0-2M0 undergoing treatment at a single institution in China (2014-2018) were reviewed. The 3-year disease-free survival (DFS) was set as the primary outcome, and the 3-year PM rate was also analyzed. RESULTS: 220 patients were included in this study for analysis. After 1:3 PSM: HIPEC (n = 45) and No HIPEC (n = 135). Through analysis, it was found that prophylactic HIPEC correlated to better DFS [hazard ratio (HR) 0.43, 95 % confidence interval (CI) 0.19-0.95; p = 0.037], and N2 stage correlated to worse DFS [HR 1.97, 95 % CI 1.09-3.56; p = 0.025]. For laparoscopic surgery subgroup analyses, 3-year PM rate of patients with laparoscopic surgery was 13.8 % in No HIPEC group, and 2.6 % in HIPEC group (p = 0.070). Besides, no post-operative death occurred, the anastomotic leakage rate was 2.2 % in HIPEC group and 0.7 % in the control group (p = 0.439). CONCLUSIONS: Prophylactic HIPEC may improve the prognosis in patients with cT4N0-1M0 CRC, but not in cT4N2M0 CRC, and it does not significantly increase surgery-related complications. Laparoscopic surgery followed by HIPEC for T4 stage CRC may not increase risk of PM.
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Neoplasias Colorretais , Hipertermia Induzida , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Colorretais/patologia , Terapia Combinada , Estudos Retrospectivos , Estudos de Coortes , Pontuação de Propensão , Prognóstico , Procedimentos Cirúrgicos de Citorredução , Taxa de SobrevidaRESUMO
Background: Patients with gastric cancer (GC) have a high recurrence rate after surgery. To predict disease-free survival (DFS), we investigated the value of body composition changes (BCCs) measured by quantitative computed tomography (QCT) in assessing the prognosis of patients with GC undergoing resection combined with adjuvant chemotherapy and to construct a nomogram model in combination with clinical prognostic factors (CPFs). Methods: A retrospective study of 60 patients with GC between February 2015 and June 2019 was conducted. Pre- and posttreatment CT images of patients was used to measure bone mineral density (BMD), subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), paravertebral muscle area (PMA), and the rate of BCC was calculated. CPFs such as maximum tumor diameter (MTD), human epidermal growth factor receptor-2 (HER2), and Ki-67 were derived from postoperative pathological findings. Independent prognostic factors affecting DFS in GC were screened via univariate and multivariate Cox regression analysis. The Kaplan-Meier method and log-rank test were used to plot survival curves and compare the curves between groups, respectively. Receiver operating characteristic (ROC) curves, calibration curves, and decision curves to evaluate the efficacy of the nomogram. Results: The results of multivariate Cox regression analysis showed that ΔBMD [hazard ratio (HR): 4.577; 95% confidence interval (CI): 1.483-14.132; P=0.008], ΔPMA (HR: 5.784; 95% CI: 1.251-26.740; P=0.025), HER2 (HR: 4.819; 95% CI: 2.201-10.549; P<0.001), and maximal tumor diameter (HR: 3.973; 95% CI: 1.893-8.337; P<0.001) were independent factors influencing DFS. ΔBMD, ΔSFA, ΔVFA, ΔTFA, and ΔPMA were -3.86%, -23.44%, -19.57%, -22.45%, and -5.94%, respectively. The prognostic model of BCCs combined with CPFs had the highest predictive performance. Decision curve analysis (DCA) indicated good clinical benefit for the prognostic nomogram. The concordance index of the prognostic nomogram was 0.814, and the area under the curve (AUC) of predicting 2- and 3-year DFS were 0.879 and 0.928, respectively. The calibration curve showed that the nomogram-predicted DFS aligned well with the actual DFS. Conclusions: The prognostic nomogram combining BCCs and CPFs was able to reliably predict the DFS of patients with GC.
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BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/uso terapêutico , Neoplasias Retais/radioterapia , Neoplasias Retais/tratamento farmacológico , Quimiorradioterapia/métodos , Estadiamento de NeoplasiasRESUMO
Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.Clinical Trial Registration: NCT04342949.
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Antineoplásicos , Exantema , Neoplasias Retais , Humanos , Quimiorradioterapia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prurido , Qualidade de Vida , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Método Duplo-CegoRESUMO
Papillary thyroid carcinoma (PTC) contributes to 88% of thyroid malignancies and its extent of surgical management has been a topic of debate in the past 2 decades. American thyroid association (ATA) recommendations have been periodically updated for its robust and evidence-based management. We present our experience in implementing 2015 ATA guidelines, assessment of surgical outcomes of hemithyroidectomy in PTC ≤ 4 cm and contemplating on the potential clinical implications of 2015 ATA guidelines. A prospective study in a cohort of Bethesda class V and VI PTC with nodule ≤ 4 cm who underwent Hemithyroidectomy between 2012 and 2020. Data on thyroid nodule evaluation, management, histopathology and follow up were used for risk stratification. Of 37 patients, 27 (72.9%) were low risk and 10 (37%) were intermediate risk ATA group. 4 (40%) intermediate risk patients had structural incomplete response and underwent completion thyroidectomy. 1 (2.7%) out of 4 completion surgery patients required adjuvant radio-ablation iodine (RAI) and 3 patients were under surveillance. Overall, 2 (5.4%) of 37 patients, 1 each from low and intermediate groups were given remnant RAI in view of aggressive histology, old age and unwillingness for a completion surgery. During follow up of 4.94 ± 2.4 years, 35 (94.5%) showed excellent response and 2 (5.4%) showed biochemical incomplete response. The difference in RFS between two groups was statistically significant with p < 0.001. Thyroid preserving surgery combined with real time risk stratification seems appropriate for low and intermediate risk PTC ≤ 4 cm.
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Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
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OBJECTIVE: The aim of this study is to evaluate the progression-free survival (PFS) of recurrent ovarian cancer (ROC) patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). MATERIALS AND METHODS: ROC patients who underwent cytoreductive surgery plus HIPEC between 2015 and 2021 were retrospectively evaluated. Patients' demographic information and clinicopathological characteristics including cancer type, histology, platinum status, presence of ascites, type of surgery, complications, chemotherapy history, and disease progression were documented. PFS was calculated using the Kaplan-Meier method. RESULTS: A total of 104 patients with ROC were included. The median age was 57 years and the median follow-up time was 15 months (range: 5-69 months). In Cox regression multivariate analyses, platinum resistance (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.91-5.76, p = 0.00), more than one relapse prior HIPEC (HR: 2.81, 95% CI: 1.65-4.87, p = 0.024), and presence of ascites (HR: 1.88, 95% CI: 1.08-3.26, p = 0.00) were found to be negative prognostic factors for PFS. In subgroup analyses of patients with the first recurrence, the median PFS was 21 months for platinum-sensitive patients and 6 months for platinum-resistant patients (p = 0.032). CONCLUSION: HIPEC at the time of first platinum-sensitive relapse may lead to favorable PFS in the treatment ROC. However, HIPEC as salvage treatment even with R0 cytoreductive surgery does not seem effective.
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Hipertermia Induzida , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Ascite/etiologia , Ascite/terapia , Hipertermia Induzida/métodos , Carcinoma Epitelial do Ovário/terapia , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva , Procedimentos Cirúrgicos de Citorredução/métodosRESUMO
The current recommendation for the use of adjuvant radioactive iodine (RAI) therapy in papillary thyroid cancer (PTC) after radical surgery is based on clinicopathological factors; however, this recommendation remains controversial. Our present study established a new biomarker, RPMB (promotor methylation burden of DNA repair genes (DRGs)), to identify a patient subgroup suitable for adjuvant RAI therapy. We defined RPMB as the ratio of methylated DRGs to the total number of DRGs. Methylation profiles of 498 PTC tumors and their clinical data were retrieved from the Cancer Genome Atlas (TCGA) database. DRGs of PTC subjects were found to be much more hypomethylated than controls across the whole profile (all p < 0.001). PTC patients with higher RPMBs tended to be ≥45 years old and female, and these PTCs were commonly unifocal, with N0 disease, wild-type BRAF, and mutated RAS. The subgroup analysis indicated that high RPMBs were significantly associated with poor disease-free survival (DFS) in male patients with PTC (HR = 4.855, 95% CI: 1.527-15.433, p = 0.007). Moreover, Kaplan-Meier analysis showed that high RPMBs could significantly predict poor DFS in male patients after R0 resection for N1 disease (HR: 5.431, 95% CI: 1.045-28.219, p = 0.024), and the p-value was very close to significance in these patients after adjuvant RAI therapy (HR: 6.269, 95% CI: 0.693-56.714, p = 0.062). Multivariate analysis indicated that both male sex (HR = 14.565, 95%CI: 2.153-98.507, p = 0.006) and high RPMBs (HR = 11.206, 95%CI: 1.622-77.405, p = 0.014) were independent unfavorable factors for DFS after adjuvant RAI therapy. Therefore, RPMB might be a potential predictor for identifying suitable male patients with PTC who can benefit from adjuvant RAI therapy.
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Background: Androgen receptor (AR) is becoming an important factor in the pathogenesis of breast cancer. Traditional Chinese medicine (TCM) is widely used in treating breast cancer patients. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which has worse prognosis than other subtypes. Herein, through this retrospective study, we summarize the therapeutic implications of AR and TCM in TNBC. Methods: The clinical and pathological data of TNBC patients who had undergone surgery at The First Affiliated Hospital of Zhejiang Chinese Medical University from 2017 to 2019 were collected and examined. The t-test, chi-square test, logistic regression model, and Kaplan-Meier survival estimates were used to analyze the data. Results: We identified 823 early breast cancer patients from January 2017 to December 2019, of whom 92 (11.2%) were pathologically confirmed to have TNBC. We excluded 5 patients according to the inclusion and exclusion criteria. In relation to the remaining 87 patients, 33 (37.9%) were AR positive. In the TNBC patients, positive AR expression was correlated with an older age (P=0.006), a higher weight (P=0.006), and lower Ki-67 expression (P=0.031). After a median follow-up time of 37 months (range, 24-60 months), 13 cases of relapse and metastasis (14.9%) were observed. We found that relapse and metastasis were correlated with being unmarried [P=0.004; hazard ratio (HR) =0.105; 95% confidence interval (95% CI): 0.023-0.487], nonporous (P=0.046; HR =0.209; 95% CI: 0.045-0.971), and negative AR expression (P=0.042; HR =1.223; 95% CI: 0.049-1.012). The AR-positive TNBC patients had better disease-free survival (DFS) than the AR-negative TNBC patients 2-5 years after surgery (P<0.05). TCM was an effective treatment for TNBC (P<0.001; HR =51.682; 95% CI: 6.660-401.025). In the AR-negative group, patients who received the TCM treatment tended to have a better DFS than those who did not receive the TCM treatment (P<0.001; HR =34.832; 95% CI: 4.448-272.756); however, no such difference was found in the AR-positive group. Conclusions: The TNBC patients with positive AR tended to have a low expression of Ki-67 and a better prognosis than AR negative TNBC patients. TCM is an effective treatment and has slight side effects.
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Purpose: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/Methods: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. Results: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. Conclusions: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.
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Purpose: To analyze the oncological outcome in elderly (>70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost. Materials/methods: In this retrospective study, patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with/without androgen deprivation therapy (ADT). The impact of age (≤70y vs. > 70y) was investigated. Oncological outcome focused on biochemical relapse-free survival (bRFS), cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated. Results: From 07/08 to 01/22, 518 pts received a HDB boost, and 380 were analyzed (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). Regarding NCCN classification, 98 pts (≤70y: 53pts; >70y: 45pts; p = 0.107) and 282 pts (≤70y: 124pts; >70y: 158pts; p = NS) were IR and HR pts respectively. Median EBRT dose was 46 Gy [37.5-46] in 23 fractions [14-25]. HDB boost delivered a single fraction of 14/15 Gy (79%). ADT was used in 302 pts (≤70y: 130pts; >70y: 172pts; p = 0.01). With MFU of 72.6 months [67-83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85-92], 99% [97-100] and 94% [92-97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). Late GU and GI toxicity rates were 32.4% (G ≥ 3 7.3%) and 10.1% (no G3) respectively. Conclusions: For IR and HR prostate cancers, HDB boost leads to high rates of disease control with few late G ≥ 3 GU/GI toxicities. For elderly pts, HDB boost remains warranted mainly in HR pts, while competing comorbidity factors influence OS.
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Aim: To investigate the efficacy and safety of adjuvant EGFR tyrosine kinase inhibitors for resected EGFR-mutated non-small-cell lung cancer. Materials & methods: Eligible phase II/III randomized controlled trials were included for the network meta-analyses (PROSPERO CRD42021275150). Results: Nine records and 831 patients were involved. Adjuvant chemotherapy followed with osimertinib significantly prolonged disease-free survival compared with chemotherapy (hazard ratio [HR]: 0.2; 95% CI: 0.14-0.29), chemotherapy followed with erlotinib (HR: 0.33; 95% CI: 0.18-0.6), chemotherapy followed with gefitinib (HR: 0.36; 95% CI: 0.16-0.82), gefitinib (HR: 0.26; 95% CI: 0.17-0.41) and icotinib (HR: 0.56; 95% CI: 0.3-0.98). Icotinib was the least likely to cause grade ≥3 adverse events. Conclusion: Chemotherapy followed with osimertinib brings about the best disease-free survival. Icotinib monotherapy shows the best safety.
Patients with early-stage non-small-cell lung cancer have about a one in five chance of cancer recurrence, even after complete resection. Using agents targeting EGFR, known as adjuvant EGFR tyrosine kinase inhibitors, after surgery is an effective way for patients with EGFR-mutated non-small-cell lung cancer to prevent recurrence. However, the optimal agent with favorable efficacy and safety is yet to be determined. This study showed that adjuvant chemotherapy followed with osimertinib had the best efficacy, while adjuvant icotinib monotherapy had the best safety.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Metanálise em Rede , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
INTRODUCTION: Patients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups. RESULTS: A total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group. CONCLUSIONS: Prophylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.
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Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy with poor prognosis. Human papilloma virus (HPV) can induce SNSCC although its incidence and impact on patients' outcomes remains unclear. We performed a retrospective cohort study of patients with SNSCC treated consecutively in a comprehensive cancer center. HPV status was determined with p16 immunohistochemistry followed by RNA in situ hybridization (RNAscope). The incidence, clinical characteristics, and oncologic outcomes of HPV+SNSCC were assessed. P16 prognostic value was evaluated. Fifty-nine patients were included. Eleven (18.6%) SNSCC were p16+ with five (8.4%) doubtful cases. RNAscope was positive in nine cases (15.2%). Patients with HPV+SNSCC were younger (p = 0.0298) with a primary tumor originating mainly in nasal fossa (p < 10−4). Pathologic findings were not different according to HPV status. Among patients who were curatively treated, overall survival was better for HPV+SNSCC (p = 0.022). No prognostic value of p16 expression was reported. Patients with HPV+SNSCC have better oncologic outcomes, probably due to earlier tumor stage with primary location predominantly in the nasal fossa, a more suitable epicenter to perform a surgical resection with clear margins. P16 expression seems not to be a good surrogate of HPV status in SNSCC.
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Background: Accurately predicting the risk of recurrence in stage I-IIIA non-small cell lung cancer (NSCLC) after resection is critical in the treatment process. This study aimed to establish a novel nomogram to identify patients with a risk of disease progression in stage I-IIIA lung cancer based on clinical characteristics, peripheral T-lymphocyte subsets, and CD16+56 natural killer (NK) cells. Methods: A total of 306 NSCLC patients from Shanghai Municipal Hospital of Traditional Chinese Medicine between 2010 and 2020 who met the inclusion and exclusion criteria between January 2011 and December 2020 were retrospectively reviewed. Patients were randomly assigned to the training cohort (206 patients) and the validation cohort (100 patients). A nomogram model was developed based on the results of multivariate Cox regression in the training cohort. The optimal cut-off values were determined by X-tile software. The bootstrap method was used to validate the nomogram. Receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC) were used to compare prognostic factors. The concordance index (C-index) was calculated to determine the accuracy of the nomogram in predicting disease-free survival (DFS). Results: Gender, drinking history, TNM stage, and CD4+T/CD8+T were independent factors for DFS and were integrated into the model, while CD16+56 NK cells were not proven to be significant independent factors for DFS. The calibration curves for probability of 3- and 5-year DFS showed excellent agreement between predicted and actual survival. The C-index for the nomogram to predict DFS was 0.839 in the training cohort. The nomogram showed an excellent predictive performance in the training cohort (3-/5-year AUC: 0.860/0.847) and in the validation cohort (3-/5-year AUC: 0.726/0.748). Conclusions: We developed a prognostic model which provided individual prediction of DFS for stage I-IIIA NSCLC patients after resection. This practical prognostic tool may help oncologists in clinical treatment planning.
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BACKGROUND: Statins are cholesterol-lowering drugs prescribed for the prevention and treatment of cardiovascular disease. Moreover, statins may possess anticancer properties and interact with receptor activator of nuclear factor κB ligand expression. We aimed at evaluating a hypothetical synergistic effect of statins with denosumab in early-stage breast cancer (BC) patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 18. PATIENTS AND METHODS: ABCSG-18 (NCT00556374) is a prospective, randomized, double-blind, phase III study; postmenopausal patients with hormone receptor-positive BC receiving a nonsteroidal aromatase inhibitor were randomly assigned to denosumab or placebo. In this post hoc analysis, we investigated the effects of concomitant statin therapy on recurrence risk (RR) of BC, fracture risk and bone mineral density (BMD). RESULTS: In the study population (n = 3420), statin therapy (n = 824) was associated with worse disease-free survival (DFS) [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.04-1.75; P = 0.023]. While no significant effect of lipophilic statins (n = 710) on RR was observed (HR 1.30, 95% CI 0.99-1.72; P = 0.062), patients on hydrophilic statins (n = 87) had worse DFS compared with patients not receiving any statins (HR 2.00, 95% CI 1.09-3.66; P = 0.026). This finding was mainly driven by the effect of hydrophilic statins on DFS in the denosumab arm (HR 2.63, 95% CI 1.21-5.68; P = 0.014). However, this effect subsided after correction for confounders in the sensitivity analysis. No association between statin use and fracture risk or osteoporosis was observed. CONCLUSION: According to this analysis, hydrophilic statins showed a detrimental effect on DFS in the main model, which was attenuated after correction for confounders. Our data need to be interpreted with caution due to their retrospective nature and the low number of patients receiving hydrophilic statins.
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Neoplasias da Mama , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias da Mama/terapia , Denosumab/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pós-Menopausa , Estudos Prospectivos , Estudos RetrospectivosRESUMO
PURPOSE: To investigate the value of body composition changes measured by quantitative computer tomography (QCT) in evaluating the prognosis of advanced epithelial ovarian cancer (AEOC) patients who underwent primary debulking surgery (PDS) and adjuvant platinum-based chemotherapy, and constructed a nomogram model for predicting survival in combination with prognostic inflammation score (PIS). METHOD: Fifty-seven patients with AEOC between 2012 and 2016 were retrospectively enrolled. Pre- and post-treatment CT images were used to analyze the body composition biomarkers. The subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), cross-sectional area of paraspinal skeletal muscle area (PMA), skeletal muscle density (SMD), body mineral density (BMD) were measured from two sets of CT images. RESULTS: In multivariate analyses, VFA gain, PMA loss, BMD loss, and PIS were independent risk factors of overall survival (OS) (HR = 3.7, 3.0, 2.8, 1.9, respectively, all p < 0.05). Receiver operating characteristic (ROC) curves showed that the prognostic model combining body composition changes (BCC) and PIS had the highest predictive performance (area under the curve = 0.890). The concordance index (C-index) of the prognostic nomogram was 0.779 (95% CI, 0.673-0.886). Decision curve analysis (DCA) demonstrated the prognostic nomogram had a great distinguishing performance. CONCLUSION: CT-based body composition analyses and PIS were associated with poor OS for AEOC patients who underwent PDS and adjuvant platinum-based chemotherapy. The prognostic nomogram with a combination of BCC and PIS was dependable in predicting survival for AEOC patients during treatment.
Assuntos
Nomogramas , Neoplasias Ovarianas , Composição Corporal , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Inflamação/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Adjuvant endocrine therapy induces bone loss and increases fracture risk in women with hormone-receptor positive, early-stage breast cancer (EBC). We aimed to update a previous position statement on the management of aromatase inhibitors (AIs) induced bone loss and now included premenopausal women. METHODS: We conducted a systematic literature search of the medical databases from January 2017 to May 2020 and assessed 144 new studies. RESULTS: Extended use of AIs beyond 5 years leads to persistent bone loss in breast cancer extended adjuvant trials and meta-analyses. In addition to bone mineral density (BMD), vertebral fracture assessment (VFA) and trabecular bone score (TBS) were shown to independently predict fracture risk in real life prospective studies. FRAX® tool does not seem to be reliable for assessing fracture risk in CTIBL. In premenopausal women, there is strong evidence that intravenous zoledronate prevents bone loss but weak conflicting evidence on reducing disease recurrence from independent randomised controlled trials (RCTs). In postmenopausal women, the strongest evidence for fracture prevention is for denosumab based on a well-powered RCT while there is strong evidence for bisphosphonates (BPs) to prevent and reduce CTIBL but no convincing data on fractures. Adjuvant denosumab has failed to show anticancer benefits in a large, well-designed RCT. DISCUSSION AND CONCLUSIONS: Extended use of AIs and persistent bone loss from recent data reinforce the need to evaluate fracture risk in EBC women initiated on AIs. Fracture risk should be assessed with clinical risk factors and BMD along with VFA, but FRAX is not adapted to CTIBL. Anti-resorptive therapy should be considered in those with a BMD T-score < -2.0 SD or with ≥ 2 clinical risk factors including a BMD T-score < -1.0 SD. In premenopausal women, intravenous zoledronate is the only drug reported to prevent bone loss and may have additional anticancer benefits. In postmenopausal women, either denosumab or BPs can be prescribed for fracture prevention with pertinent attention to the rebound phenomenon after stopping denosumab. Adjuvant BPs, in contrast to denosumab, have shown high level evidence for reducing breast cancer recurrence in high-risk post-MP women which should be taken into account when choosing between these two.
RESUMO
BACKGROUND: Laparoscopic surgery has been widely accepted to treat early-stage gastric cancer. However, it is still controversial to perform laparoscopic gastrectomy plus D2 lymphadenectomy for locally advanced gastric cancer. We performed the present study to compare the long-term outcomes of patients after laparoscopic or open gastrectomy plus D2 lymphadenectomy. METHODS: The clinicopathological data of 182 gastric cancer patients receiving gastrectomy plus D2 lymphadenectomy between January 2011 and December 2015 at Shenzhen Traditional Chinese Medicine Hospital were retrospectively retrieved. The overall survival (OS) and disease-free survival (DFS) of these 182 patients were compared. Then, the prognostic significance of positive lymph node ratio (LNR) was assessed. RESULTS: As a whole, OS (P = 0.789) and DFS (P = 0.672) of patients receiving laparoscopic gastrectomy plus D2 lymphadenectomy were not significantly different from those of patients receiving open surgery. For stage I patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.573) and DFS (P = 0.157). Similarly, for stage II patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.567) and DFS (P = 0.830). For stage III patients, laparoscopic gastrectomy plus D2 lymphadenectomy was not significantly different from open surgery in terms of OS (P = 0.773) and DFS (P = 0.404). Laparoscopic or open gastrectomy plus D2 lymphadenectomy was not proven by Cox regression analysis to be an independent prognostic factor for OS and DFS. High LNR was significantly associated with worse OS (P < 0.001) and DFS (P < 0.001). Surgical type did not significantly affect prognosis of patients with low LNR or survival of patients with high LNR. CONCLUSIONS: For patients with gastric cancer, laparoscopic gastrectomy plus D2 lymphadenectomy was not inferior to open surgery in terms of long-term outcomes. LNR is a useful prognostic marker for GC patients.