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BACKGROUND: Recent advancements in magnetic resonance imaging (MRI) for staging have highlighted the critical question of the need for prophylactic cranial irradiation (PCI) in managing early to mid-stage small cell lung cancer (SCLC). This study assesses the impact of PCI on overall survival (OS) and intracranial control among patients with stage I-IIB SCLC. METHODS: Data from 148 stage I-IIB SCLC patients treated with thoracic radiation therapy (TRT) at two centers were examined. Patients were categorized based on PCI administration: 63 received PCI, while 85 did not. All underwent pretreatment MRI, achieving at least a partial response to therapy. A 1:1 propensity score matching analysis corrected for potential biases. RESULTS: Propensity scores were generated to 116 patients, considering patient demographics, disease progression, and treatment methods. Death was included as a competing risk. The 3-year brain metastases (BM) occurrence rate was significantly higher in patients who did not receive PCI (30.0%) compared to those who did (14.8%), however, the difference was not statistically significant (No PCI vs. PCI, hazard ratio [HR]: 2.08, 95% CI [0.93-4.55], P = .07). No significant effect of PCI on OS was observed [PCI vs. No PCI, HR: 0.80, 95% CI (0.45-1.43), P = .45]. A subgroup analysis of stage IIB patients showed a significant increase in BM risk and mortality for those not receiving PCI (No PCI vs. PCI, BM risk HR: 5.85, 95% CI: 1.83-18.87, P = .003; mortality HR: 2.78, 95% CI: 1.14-6.67, P = .02), with less pronounced effects in stages I-IIA. CONCLUSION: With modern MRI-based screening, PCI may markedly benefit stage IIB SCLC patients by reducing BM and improving OS after initial sensitive treatment. This benefit does not appear to extend to stage I-IIA patients.
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BACKGROUND: The 9th edition of the lung cancer tumor-node-metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. METHODS: Stage II non-small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan-Meier analysis with log-rank testing compared overall survival (OS) and cancer-specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)-based Cox analyses identified prognostic factors. RESULTS: Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p < 0.001; CSS, p = 0.005). LASSO-based Cox analyses confirmed stage IIA New patients had inferior prognosis compared to stage IIA patients (OS HR: 1 vs. 1.325, p < 0.001; CSS HR: 1 vs. 1.327, p < 0.001). CONCLUSIONS: The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging remains unverified in Caucasians. Caution is warranted in assessing the staging and prognosis of these individuals. Further validation of our findings is necessary.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Población Blanca , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Femenino , Anciano , Persona de Mediana Edad , Metástasis Linfática , Pronóstico , Estimación de Kaplan-Meier , Puntaje de PropensiónRESUMEN
PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.
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Carcinoma de Células Escamosas , Quimioradioterapia , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Estudios Retrospectivos , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Quimioradioterapia/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Adulto , Anciano , Puntaje de Propensión , Resultado del TratamientoRESUMEN
INTRODUCTION: A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. METHODS: The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan-Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. RESULTS: The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). CONCLUSION: Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration.
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Neoplasias del Colon , Estadificación de Neoplasias , Humanos , Neoplasias del Colon/patología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/terapia , Femenino , Masculino , Anciano , Persona de Mediana Edad , Quimioterapia Adyuvante , Estados Unidos/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia , Colectomía , Anciano de 80 o más Años , Escisión del Ganglio Linfático , Estimación de Kaplan-MeierRESUMEN
PURPOSE: To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods. RESULTS: A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41-2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45-12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14-25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29-2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55-42.26; P = 0.157) compared to CCRT. CONCLUSION: AC did not improve survival in patients with stage IIB CSCC receiving CCRT.
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Carcinoma de Células Escamosas , Neoplasias Nasofaríngeas , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , China , Quimioradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Nasofaríngeas/patología , Estudios RetrospectivosRESUMEN
Stage IIB/IIC melanoma has a high risk of recurrence after surgical resection. While, for decades, surgery was the only option for high-risk stage II disease in most countries, adjuvant therapies now exist. Anti-programmed cell death protein 1 (PD-1) antibodies significantly improve recurrence-free survival versus placebo in patients with fully resected stage IIB/IIC melanoma. Combined BRAF MEK inhibitor therapy showed benefits in high-risk stage III and advanced disease; however, its role in patients with fully resected stage BRAF-mutated IIB/IIC melanoma is still unknown. Here we describe the rationale and design of the ongoing randomized, placebo-controlled COLUMBUS-AD trial, the first study of a BRAF-MEK inhibitor combination therapy (encorafenib + binimetinib) in patients with BRAF V600-mutated stage IIB/IIC melanoma.
Melanoma is a type of skin cancer. Although most stage II melanomas (cancer affecting the first two layers of skin) can be cured with surgery, the risk of the cancer returning and spreading to other areas of the body is high in some patients with stage IIB/IIC melanoma. Furthermore, once the melanoma has spread, it is much more difficult to treat successfully and remove all the cancer cells from the body. Some melanomas have a DNA alteration (or mutation) in what is known as the BRAF gene. This mutation can be identified by testing a sample of the tumor tissue removed during a biopsy or surgery. Testing for BRAF mutations at diagnosis can help ensure that patients receive the most appropriate treatment for their cancer. In some countries, surgery is the only option for patients with stage II melanoma, while in other countries, patients may be offered additional (adjuvant) anticancer treatment with immunotherapy (agents that work with the immune system to kill cancer cells). While immunotherapy can reduce the risk of melanoma recurrence, persistent, long-term toxicities are common and the use of this treatment in all stage IIB/IIC melanoma patients is not always possible. Here, we describe the rationale and design of an ongoing clinical trial (COLUMBUS-AD), which will be the first study (to our knowledge) to investigate the efficacy and safety of a treatment that specifically targets cancers with BRAF mutations (i.e., the BRAF-MEK inhibitor combination of the drugs encorafenib and binimetinib) in patients with BRAF-mutated stage IIB/IIC melanoma. Clinical Trial Registration: NCT05270044 (ClinicalTrials.gov).
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Melanoma , Neoplasias Cutáneas , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melanoma/tratamiento farmacológico , Melanoma/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Ensayos Clínicos Fase III como Asunto , Melanoma Cutáneo MalignoRESUMEN
INTRODUCTION: Whether changes should be made to the TNM classification of non-small cell lung cancer (NSCLC) according to the newly proposed nodal classification is unclear. We aim to compare the survival between stage-IIB subsets using a modelling study performed using the newly proposed nodal classification. PATIENTS AND METHODS: A total of 682 patients with stage-IIB NSCLC based on the 8th TNM classification were analysed. Hazard ratio (HR) values calculated from survival comparisons between stage-IIB subgroups were used to create a model for patients with stage-IIB NSCLC, and modelling was performed according to the HR values that were close to each other. RESULTS: Patients with T1N1a cancer had the best survival rate (58.2%), whereas the worst prognosis was observed in those with T2bN1b cancer (39.2%). The models were created using the following HR results: Model A (T1N1a, n = 85; 12.4%), Model B (T2a/T2bN1a and T3N0, n = 438; 64.2%), and Model C (T1/T2a/T2bN1b, n = 159; 23.4%). There was a significant difference between the models in terms of overall survival (p = 0.03). The median survival time was 69 months in Model A, 56 months in Model B, and 47 months in Model C (Model A vs. Model B, p = 0.224; Model A vs. Model C, p = 0.01; and Model B vs. Model C, p = 0.04). Multivariate analysis showed that age (p < 0.001), pleural invasion (p < 0.001), and the developed modelling system (p = 0.02) were independently negative prognostic factors. CONCLUSION: There was a prognostic difference between stage-IIB subsets in NSCLC patients. The model created for stage-IIB lung cancer showed a high discriminatory power for prognosis.
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INTRODUCTION: Pembrolizumab was approved in the US as adjuvant treatment of patients with stage IIB or IIC melanoma post-complete resection, based on prolonged recurrence-free survival vs. placebo in the Phase 3 KEYNOTE-716 trial. This study aimed to evaluate the cost-effectiveness of pembrolizumab vs. observation as adjuvant treatment of stage IIB or IIC melanoma from a US health sector perspective. METHODS: A Markov cohort model was constructed to simulate patient transitions among recurrence-free, locoregional recurrence, distant metastasis, and death. Transition probabilities from recurrence-free and locoregional recurrence were estimated via multistate parametric modeling based on patient-level data from an interim analysis (data cutoff date: 04-Jan-2022). Transition probabilities from distant metastasis were based on KEYNOTE-006 data and network meta-analysis. Costs were estimated in 2022 US dollars. Utilities were based on applying US value set to EQ-5D-5L data collected in trial and literature. RESULTS: Compared to observation, pembrolizumab increased total costs by $80,423 and provided gains of 1.17 quality-adjusted life years (QALYs) and 1.24 life years (LYs) over lifetime, resulting in incremental cost-effectiveness ratios of $68,736/QALY and $65,059/LY. The higher upfront costs of adjuvant treatment were largely offset by reductions in costs of subsequent treatment, downstream disease management, and terminal care, reflecting the lower risk of recurrence with pembrolizumab. Results were robust in one-way sensitivity and scenario analyses. At a $150,000/QALY threshold, pembrolizumab was cost-effective vs. observation in 73.9% of probabilistic simulations that considered parameter uncertainty. CONCLUSION: As an adjuvant treatment of stage IIB or IIC melanoma, pembrolizumab was estimated to reduce recurrence, extend patients' life and QALYs, and be cost-effective versus observation at a US willingness-to-pay threshold.
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Análisis de Costo-Efectividad , Melanoma , Humanos , Estados Unidos , Análisis Costo-Beneficio , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Melanoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Años de Vida Ajustados por Calidad de VidaRESUMEN
The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Colon , Humanos , Masculino , Persona de Mediana Edad , Femenino , Oxaliplatino/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/cirugía , Quimioterapia Adyuvante , Adyuvantes Inmunológicos/uso terapéutico , Estadificación de Neoplasias , Fluorouracilo/uso terapéutico , PronósticoRESUMEN
Aim: To describe clinical outcomes after complete surgical resection of stage IIB and IIC melanoma. Methods: Adult patients (n = 567) with stage IIB or IIC cutaneous melanoma initially diagnosed and completely resected from 2008-2017 were identified using data from a US community-based oncology network. Results: Median patient follow-up was 38.8 months from melanoma resection to death, last visit or data cut-off (31 December 2020). For stage IIB (n = 375; 66%), Kaplan-Meier median real-world recurrence-free survival (rwRFS) was 58.6 months (95% CI, 48.6-69.5). For stage IIC (n = 192; 34%), median rwRFS was 29.9 months (24.9-45.5). Overall, 44% of patients had melanoma recurrence or died; 30% developed distant metastases. Conclusion: Melanoma recurrence was common, highlighting the need for effective adjuvant therapy for stage IIB and IIC melanoma.
New treatments are now available that decrease tumor recurrence when administered after surgery to remove melanoma skin tumors that are graded as stage IIB or IIC (i.e., with no cancer spread to the local lymph nodes). We studied 567 'real-world' patients at clinics in the USA who had stage IIB or IIC melanoma tumors removed in 20082017, before these new postsurgical treatments were widely available, to evaluate their survival and tumor recurrence. We found that almost half of these patients (44%) had melanoma recurrence or had died, and a third (30%) had tumor spread beyond the original site, by the end of 2020. These findings highlight the need for more effective treatments after surgical removal of stage IIB and IIC melanoma.
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Melanoma , Neoplasias Cutáneas , Adulto , Humanos , Melanoma/terapia , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Terapia Combinada , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: This work used software-guided radiographic measurement to assess the effects of progressive lateral column lengthening (LCL) on restoring alignment in a novel cadaveric model of stage II-B flatfoot deformity. METHODS: A stage II-B flatfoot was created in 8 cadaveric specimens by transecting the spring ligament complex, anterior deltoid, and interosseous talocalcaneal and cervical ligaments. Weightbearing computed tomographic (WBCT) scans were performed with specimens under 450 N of compressive load in the intact, flat, and 6-, 8-, and 10-mm lateral column-lengthening conditions. Custom software-guided radiographic measurements of the lateral talo-first metatarsal (Meary) angle, anteroposterior talo-first metatarsal angle, naviculocuneiform overlap, and 2 new measures (plantar fascia [PF] distance and angle) were recorded on digitally reconstructed radiographs. Four anonymized analysts performed measurements twice. Intra- and interobserver agreement was assessed using intraclass correlation coefficients (ICCs). RESULTS: Six-millimeter LCL restored alignment closest to the intact foot in this new cadaveric model, whereas 10-mm lengthening tended toward overcorrection. The PF line displaced laterally in the flatfoot condition, and LCL restored the PF line to a location beneath the talonavicular joint. Interobserver agreement was excellent for PF distance (ICC = 0.99) and naviculocuboid overlap (ICC = 0.91), good for Meary angle (ICC = 0.81) and PF angle (ICC = 0.69), and acceptable for the talonavicular coverage angle (ICC = 0.65). CONCLUSION: In this stage II-B cadaveric flatfoot model, cervical ligament transection was essential to create deformity after the medial hindfoot ligaments were transected. Software-guided radiographic measurement proved reliable; standardized implementation should improve comparability between studies of flatfoot deformity. The novel PF distance performed most consistently (ICC = 0.99) and warrants further study. With this model, we found that a 6-mm LCL restored alignment closest to the intact foot, whereas 10-mm lengthening tended toward overcorrection. CLINICAL RELEVANCE: Future joint-sparing flatfoot corrections may consider using a relatively small LCL combined with other bony and/or anatomic ligament/tendon reconstructions.
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Pie Plano , Cadáver , Pie Plano/diagnóstico por imagen , Pie Plano/cirugía , Pie , Humanos , Ligamentos Articulares , Programas InformáticosRESUMEN
The incidence of lymph node (LN) involvement and its prognostic value based on radiological imaging in stage IIB cervical cancer (CC) remains unclear, and evidence regarding oncological outcomes of patients with stage IIB CC with LN metastases is limited. In this study we retrospectively reviewed the incidence and prognostic significance of pretreatment radiologic LN status in 72 patients with clinical stage IIB CC (FIGO 2009), with or without radiologic evidence of LN enlargement. An enlarged LN was defined as a diameter > 10 mm on CT/MRI. Progression-free survival (PFS) and overall survival (OS) were assessed. Radiologic LN enlargement of >10 mm was observed in 45.8% of patients with stage IIB CC. PFS (p = 0.0088) and OS rates (p = 0.0032) were significantly poorer in the LN group (n = 33) than in the non-LN group (n = 39). Univariate Cox analysis revealed that LN > 10 mm contributed to a higher rate of recurrence and mortality. In conclusion, nearly half of the patients with clinical stage IIB CC had enlarged LNs (>10 mm) identified during pretreatment radiologic evaluation, which negatively impacted prognosis. Our findings highlight the need to incorporate CT- or MRI-based LN assessment before treatment for stage IIB CC.
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BACKGROUND: Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT. METHODS: This is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB-IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied. DISCUSSION: The data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326.
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Cisplatino , Neoplasias del Cuello Uterino , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Estudios Multicéntricos como Asunto , Terapia Neoadyuvante , Estadificación de Neoplasias , Paclitaxel , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: We conducted this large population-based study to re-evaluate the survival paradox between stage IIB/C and stage IIIA colon cancer based on the newest staging criteria. METHODS: Colon cancer patients were recruited from the Surveillance, Epidemiology, and End Results (SEER) database using SEER*Stat software (version 8.3.4) with strict inclusion criteria. We used Chi-square test to compare categorical variables between patients diagnosed with stage IIB/IIC and stage IIIA colon cancer. Survival probabilities were then assessed using the Kaplan-Meier method. Cox proportional hazards models were used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs) of clinicopathologic characteristics in stage IIB/IIC and stage IIIA colon cancer patients. RESULTS: In the current study, a total of 9,227 eligible colon cancer patients were collected from the SEER database between 2010 and 2015. It was found that stage IIIA had 66.4% decreased risk of colon cancer-specific mortality compared with stage IIB (HR = 0.336, 95%CI = 0.286-0.394 for stage IIIA, P < 0.001, using stage IIB as the reference) after the adjustment for other known prognostic factors. And T1N2a colon cancer had significantly lower 5-year overall survival (OS) rate compared with T2N1 disease (74.7% vs. 57.1%, P = 0.018). CONCLUSIONS: Our study confirmed the existence of survival paradox between stage IIB/IIC and stage IIIA colon cancer based on the newest staging criteria. What is more, the subgroup analyses revealed that T1N2a had the least influence on the survival paradox. N2a colon cancer seemed to be associated with worse prognosis than T2 disease, which would give us a better understanding of tumor biology of colon cancer and be conducive to the refinement of individualized treatment regimens in stage III disease.
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PURPOSE: Although local inflammatory response (LIR) is a reliable survival marker in colon cancers (CCs), there is no consensus on its use in daily practice. We investigated the prognostic value of LIR in a highly homogeneous population with a well-designed methodology. METHODS: Eighty stage-IIB CC patients operated between 2002 and 2012 were included in the study. Standardization was investigated for extra-biopsy evaluation methods (magnification, staining, and counting). Model A was used for intra-biopsy evaluation methods (block, section, and focus). So, this study makes important contributions to the standardization of pathological evaluations. RESULTS: In method 1, the following analyzes showed more successful results for LIR: relationship with prognostic factors [tumour deposits (p=0.017), Crohn's-like reaction (p=0.019), advanced grade, (p=0.012), positive surgical margin (p=0.019), perineural invasion (p=0.025), mismatch repair proteins-proficiency (p=0.031)], reproducibility of the study (Kappa=0.49-0.73, Intra-class correlation=0.442-0.724), and correlation of estimates (r=0.704). The cut-off value was also quite useful (area of under ROC=0.820 [0.694-0.920]). In univariate analysis, low LIR was related to poor overall survival (OS; p<0.001) and poor relapse-free survival (RFS, p=0.001) . Multivariate analysis confirmed that low LIR is an independent poor survival marker for OS (Hazard Ratio [HR]=1.32 [1.08-1.61, p=0.005) and RFS (HR=1.50 [1.22-1.85], p<0.001). CONCLUSIONS: Our results showed that low LIR had an independent prognostic significance in stage -IIB CCs. We also recommend using model A and method 1 for successful results and standardization.
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Adenocarcinoma/inmunología , Neoplasias del Colon/inmunología , Inflamación/inmunología , Resultado del Tratamiento , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Supervivencia sin Enfermedad , Femenino , Humanos , Inflamación/patología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: The purposes of this study were to evaluate the appropriateness of the stage migration of stage IIA non-small cell lung cancer (NSCLC) in the seventh edition of the tumor, node, and metastasis classification for lung cancer to stage IIB lung cancer in the eighth edition, and to identify prognostic factors in patients with eighth-edition stage IIB disease. METHODS: Patients with eighth-edition stage IIB disease were subclassified into those with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease, and their recurrence-free survival and disease-specific survival rates were compared. Risk factors for recurrence after curative resection were identified in all included patients. RESULTS: Of 122 patients with eighth-edition stage IIB NSCLC, 101 (82.8%) had seventh-edition stage IIA disease and 21 (17.2%) had seventh-edition stage IIB disease. Nonsignificant differences were observed in the 5-year recurrence-free survival rate and the 5-year disease-specific survival rate between the patients with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease. Visceral pleural invasion was a significant risk factor for recurrence in patients with eighth-edition stage IIB NSCLC. CONCLUSION: The stage migration from seventh-edition stage IIA NSCLC to eighth-edition stage IIB NSCLC was appropriate in terms of oncological outcomes. Visceral pleural invasion was the only prognostic factor in patients with eighth-edition stage IIB NSCLC.
RESUMEN
BACKGROUND: A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. METHODS: Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). RESULTS: Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. CONCLUSIONS: The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.
Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/mortalidad , Metilación de ADN , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios RetrospectivosRESUMEN
OBJECTIVE: To examine predictors of pathological parametrial invasion in clinical stage IIB cervical cancer, and to examine prognostic factors in pathological stage IIB disease. METHODS: This study is an ancillary analysis of a nation-wide retrospective cohort examining 6,003 clinical stage IB-IIB cervical cancers. Women with clinical stage IIB disease who underwent primary radical hysterectomy with lymphadenectomy were examined (nâ¯=â¯714). Multivariate analysis was performed to identify independent clinico-pathological factors for pathological parametrial invasion and to identify independent prognostic factors in pathological stage IIB disease. RESULTS: Parametrial invasion was identified on the surgical specimen in 400 cases (56.0%, 95% confidence interval 52.4-59.7). On multivariate analysis, deep stromal invasion (DSI, adjusted-OR 3.922), multiple pelvic nodal metastases (adjusted-OR 3.266), lympho-vascular space invasion (adjusted-OR 2.333), and uterine corpus invasion (adjusted-OR 1.656) remained independent tumor factors for pathological parametrial invasion. In classification-tree models, tumors with DSI and multiple pelvic nodal metastases had the highest incidence of pathological parametrial invasion (75.0-87.7%); contrary, tumors without DSI had the lowest incidence (21.9%). Among patients with pathological stage IIB disease, the absolute difference in 5-year disease-free survival rates was 57.2%, ranging between 80.9% in those with squamous histology with none/single pelvic nodal metastasis and 23.7% in those with non-squamous histology with multiple pelvic nodal metastases. CONCLUSION: In clinical stage IIB cervical cancer, accuracy for pathological parametrial invasion is low-modest. With absence of DSI, only one in five clinical stage IIB diseases has pathological stage IIB disease. Survival of pathological stage IIB varies widely and is largely dependent on nodal factors.
Asunto(s)
Histerectomía/métodos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/cirugía , Displasia del Cuello del Útero/mortalidad , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugíaRESUMEN
BACKGROUND: The purposes of this study were to evaluate the appropriateness of the stage migration of stage IIA non-small cell lung cancer (NSCLC) in the seventh edition of the tumor, node, and metastasis classification for lung cancer to stage IIB lung cancer in the eighth edition, and to identify prognostic factors in patients with eighth-edition stage IIB disease. METHODS: Patients with eighth-edition stage IIB disease were subclassified into those with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease, and their recurrence-free survival and disease-specific survival rates were compared. Risk factors for recurrence after curative resection were identified in all included patients. RESULTS: Of 122 patients with eighth-edition stage IIB NSCLC, 101 (82.8%) had seventh-edition stage IIA disease and 21 (17.2%) had seventh-edition stage IIB disease. Nonsignificant differences were observed in the 5-year recurrence-free survival rate and the 5-year disease-specific survival rate between the patients with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease. Visceral pleural invasion was a significant risk factor for recurrence in patients with eighth-edition stage IIB NSCLC. CONCLUSION: The stage migration from seventh-edition stage IIA NSCLC to eighth-edition stage IIB NSCLC was appropriate in terms of oncological outcomes. Visceral pleural invasion was the only prognostic factor in patients with eighth-edition stage IIB NSCLC.