RESUMO
Breast cancer is the most common type of cancer among women. The molecular subtypes of breast cancer, depending on the Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status, usually play a vital role for the adjuvant treatment. Interestingly, there is a good possibility of change of receptor status in the recurrence of same primary tumor. The study is designed April 2018 to March 2019 to see the concordance in triple-receptor expression (ER, PR, and HER-2) between the primary and the locally recurrent breast cancer patient and the results can be able to influence the management and prognosis of the breast cancer patients. This observational study was carried out in the department of surgical oncology, NICRH where total 48 patients were studied who were subjected to core biopsy of recurrent lesion for ER, PR and HER-2 status. A structured case record form was used to interview and collect data. Data analysis was done using SPSS version 26.0 to see concordance and discordance in triple-receptor expression between the primary and the locally recurrent breast cancer patient. Among 48 cases, 12(25.0%), 10(20.83%) and 2(4.16%) patients showed Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (Her-2) discordance that are statistically significant in every receptor status. Majority discordance of ER, PR and Her-2 were associated with invasive duct cell carcinoma (IDC); ER & Her-2 discordance was equally associated with histological grade 2 and 3 whereas PR discordance had significant association with grade 3. Staging of disease showed that all ER, PR and Her-2 discordance were associated with stage (p<0.05). Besides, majority discordance was mostly associated with lumpectomy except Her-2 discordance. Besides, among the adjuvant treatment regimen chemotherapy along with radiotherapy was mostly associated with discordance of all receptors (p<0.05). Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status of primary breast cancer showed 25.0%, 20.83% and 4.16% discordant in recurrent episodes in this study. Invasive duct cell carcinoma, histological grade 2 and 3, stage II, stage III, MRM and CT along with RT are major attributable factors in this study.
Assuntos
Neoplasias da Mama , Recidiva Local de Neoplasia , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Receptores de Progesterona/metabolismo , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Quimioterapia Adjuvante , IdosoAssuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Neoplasias da Mama , Humanos , Neoplasias da Mama/tratamento farmacológico , Feminino , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Difosfonatos/efeitos adversos , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/efeitos adversosRESUMO
BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.
Assuntos
Gastrectomia , Quimioterapia Intraperitoneal Hipertérmica , Laparoscopia , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Pontuação de Propensão , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Gastrectomia/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Laparoscopia/métodos , Terapia Neoadjuvante/métodos , Taxa de Sobrevida , Prognóstico , Quimioterapia Intraperitoneal Hipertérmica/métodos , Seguimentos , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Terapia Combinada , Idoso , Quimioterapia Adjuvante/métodos , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/mortalidade , AdultoRESUMO
BACKGROUND: To date, no meta-analysis has been conducted to compare the effectiveness and safety of adjuvant tyrosine kinase inhibitors (TKIs) and adjuvant immunotherapies (IMTs) in renal cell carcinoma (RCC) patients using reconstructed individual patient data (IPD). This study aims to fill that gap by assessing the efficacy and safety profiles of these treatments in such patients. METHODS: This study employed a systematic approach for identifying relevant literature from the PubMed and EMBASE databases. We included articles published in English from the inception of these databases until November 11, 2023, focusing specifically on appropriate phase III randomized controlled trials (RCTs). To reconstruct survival curves, we utilized a semiautomated tool, WebPlotDigitizer, in conjunction with a novel shiny application integrated with R software. For adverse events (AEs), the summary measures were incidences, expressed as a 95% confidence interval (CI), calculated using a random-effects model with a logit transformation. RESULTS: The analysis included 8 RCTs with a total of 9119 patients. Compared to adjuvant TKIs, adjuvant IMTs showed a similar disease-free survival (DFS) (hazard ratio [HR] 1.03, 95% CI [0.98-1.09], Pâ =â .281). However, the overall survival (OS) rates between the 2 groups couldn't be directly compared due to unmatched control groups in the IMT and TKI studies. Against placebo, adjuvant IMTs demonstrated superior DFS (HR 0.82, 95% CI [0.71-0.94], Pâ =â .004) but comparable OS (HR 0.79, 95% CI [0.59-1.06], Pâ =â .120). Against placebo, adjuvant TKIs showed superior DFS (HR 0.85, 95% CI [0.79-0.92], Pâ <â .0001) and marginally better OS (HR 0.89, 95% CI [0.80-0.996], Pâ =â .042). Regarding severe AEs and discontinuation rates due to AEs, adjuvant IMTs had a significantly lower incidence of severe AEs (25% [320/1282] vs 59% [2192/3716], odds ratio [OR] 0.23, 95% CI [0.20-0.27], Pâ <â .0001) and a markedly better discontinuation rate (39% [499/1282] vs 52% [2068/4018], OR 0.60, 95% CI [0.53-0.68], Pâ <â .0001) compared to TKIs. CONCLUSION: This paper presents a thorough analysis of DFS, OS, and treatment-related AEs across various groups in RCC patients, offering a valuable resource for clinicians in everyday practice. Our findings indicate that while adjuvant IMTs and adjuvant TKIs demonstrate similar DFS, IMTs are notably superior in terms of safety and compliance.
Assuntos
Carcinoma de Células Renais , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Inibidores de Proteínas Quinases , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Quimioterapia Adjuvante/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalo Livre de DoençaRESUMO
OBJECTIVE: To investigate the impact of vasculogenic mimicry (VM) and postoperative adjuvant therapy on the prognosis and survival of patients with esophageal squamous cell carcinoma (ESCC), as well as to assess whether VM affects the clinical benefit of postoperative adjuvant therapy. METHODS: This single-center retrospective analysis included patients who underwent radical surgery for ESCC, which was documented in the medical record system. The presence or absence of VM in surgical specimens was determined using double staining with PAS/CD31. Stratification was applied based on adjuvant therapy and VM status. Survival curves and COX modeling were used to analyze the impact of the presence or absence of VM on the benefit of adjuvant therapy and the survival prognosis of patients. RESULTS: VM-positive patients were more prone to postoperative recurrence and metastasis. VM was identified as an independent risk factor for progression-free survival (PFS) (p < 0.001, 95% CI:1.809-3.852) and overall survival (OS) (p < 0.001, 95% CI:1.603-2.786) in postoperative ESCC. Postoperative adjuvant therapy significantly prolonged PFS (p = 0.008) and OS time (p < 0.001) in patients with stage II and III ESCC, with concurrent chemoradiotherapy being the most effective. However, the presence of VM significantly reduced the benefits of postoperative adjuvant therapy (p < 0.001). CONCLUSION: VM negatively impacts the prognosis of postoperative ESCC patients and reduces the efficacy of postoperative adjuvant therapy.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Recidiva Local de Neoplasia , Humanos , Masculino , Feminino , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Prognóstico , Idoso , Neovascularização Patológica , Quimioterapia Adjuvante/métodos , Esofagectomia , Resistencia a Medicamentos Antineoplásicos , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease. METHODS: We identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis. RESULTS: Overall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15-90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without. CONCLUSIONS: Patients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases.
Assuntos
Histerectomia , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/mortalidade , Adulto , Sarcoma/cirurgia , Sarcoma/mortalidade , Sarcoma/patologia , Idoso , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Quimioterapia Adjuvante , Miomectomia Uterina , Análise de SobrevidaRESUMO
Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common subtype, representing over two-thirds of new diagnoses. Adjuvant therapy, which encompasses various medications and treatment durations, is the standard approach for managing early stage HR+ HER2- breast cancer. Optimizing treatment is essential to minimize unnecessary side effects while addressing the biological variability inherent in HR+/HER2- breast cancers. Incorporating biological biomarkers into treatment decisions, alongside traditional clinical factors, is vital. Gene expression assays can identify patients unlikely to benefit from adjuvant chemotherapy, thereby refining treatment strategies and improving risk assessment. This paper reviews evidence for several genomic tests, including Oncotype DX, MammaPrint, Breast Cancer Index, RucurIndex, and EndoPredict, which assist in tailoring adjuvant therapy. Additionally, we explore the role of liquid biopsies in personalizing treatment, emphasizing the importance of considering late relapse risks and potential benefits of extended systemic therapy for HR+/HER2- breast cancer patients.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Sequenciamento de Nucleotídeos em Larga Escala , Recidiva Local de Neoplasia , Receptor ErbB-2 , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Quimioterapia Adjuvante/métodos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Medição de Risco/métodos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Medicina de Precisão/métodos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
This study aimed to survey the efficacy of chemotherapy regimens in the real world setting and explore the most promising regimen for patients experiencing early recurrence for gastric cancer. We retrospectively reviewed the clinical course of 207 patients with gastric cancer, who developed early recurrence during or within 6 months after completing S-1 adjuvant therapy at 19 Japanese institutions between 2012 and 2016. The treatment regimens after recurrence were fluoropyrimidines plus platinum-based regimens (FP) in 91 (44%) patients, paclitaxel-based regimens (PTX) in 102 (49%), and irinotecan-based regimens (IRI) in 14 (7%). The overall response and disease control rates were 28.7% and 54.1%. Median progression-free survival (PFS) and overall survival (OS) were 5.1 and 12.9 months, respectively. In the FP, PTX, and IRI regimens, the median PFS and OS were 5.9, 4.1, 4.1 months and 12.8, 12.9, and 11.8 months, respectively. The combination of PTX and ramucirumab showed survival comparable to capecitabine plus platinum. Multivariate analyses for OS showed that recurrence during adjuvant chemotherapy and undifferentiated histological type were independent poor prognostic factors. Although the prognosis of patients with early recurrence even with adjuvant S-1 was poor, PTX plus ramucirumab therapy could be a potential treatment option.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Recidiva Local de Neoplasia , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Masculino , Feminino , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimioterapia Adjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Resultado do Tratamento , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , RamucirumabRESUMO
RATIONALE: Neuroendocrine carcinoma originating from extrahepatic bile duct is very rare, and only a few cases have been reported. Because of its scarcity of incidence, not much is known about the disease but for its aggressiveness and poor prognosis. PATIENT CONCERNS: In this report, we present 2 cases of large cell neuroendocrine carcinoma (LCNEC) originating from extrahepatic bile duct. Case 1: a 60-year-old woman presented with jaundice but no abdominal pain. Case 2: a 67-year-old man also presented with jaundice, along with abdominal discomfort and appetite loss. DIAGNOSES: Case 1: LCNEC with a focal adenocarcinoma component (pT2aN1M0, pStage IIIB). Case 2: LCNEC with a focal adenocarcinoma component (pT1N1M0, pStage IIB). INTERVENTIONS: Case 1: the patient underwent left hepatectomy and caudatectomy with hepaticojejunostomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). Case 2: the patient underwent laparoscopic pylorus-preserving pancreatoduodenectomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). OUTCOMES: Case 1: liver metastasis was detected 6 months postoperatively, and despite multiple chemotherapy regimens, the patient died 24 months post-surgery. Case 2: liver metastasis was detected 23 months postoperatively. The patient is still alive 36 months post-surgery after receiving multiple chemotherapy regimens and radiotherapy. LESSONS: Given the rarity of LCNEC, it is essential to continue collecting and reporting additional case studies to build a more comprehensive understanding of the disease. Although the prognosis for LCNEC is generally poor, the use of a multidisciplinary approach and further research will be critical in developing more effective treatment strategies in the future.
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Neuroendócrino , Humanos , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/terapia , Feminino , Quimioterapia Adjuvante/métodos , Pessoa de Meia-Idade , Idoso , Masculino , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/terapia , Evolução Fatal , Hepatectomia/métodos , Pancreaticoduodenectomia/métodos , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Aims/Background We aimed to investigate the impact of postoperative chemotherapy (POCT) on survival in patients with primary central nervous system lymphoma (PCNSL) using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods This study included 786 PCNSL patients, of which 605 received chemotherapy after surgery, and 181 did not. Data from the SEER registry database (2007-2020) were used to analyze PCNSL. Baseline information, including age, sex, race, marital status, primary tumour site, histological type, summary stage, surgical procedures, chemotherapy, and radiotherapy, was analyzed. Propensity Score Matching (PSM) (1:1) was employed to balance the effects of confounding variables between the two groups. Subsequently, Cox regression and bidirectional stepwise regression were used to identify independent prognostic factors. Kaplan-Meier (K-M) survival curves were constructed to assess the impact of POCT on patient prognosis. Additionally, two cases of PCNSL with typical magnetic resonance imaging appearances were presented. Results Multivariate Cox regression results revealed that age older than 60 years (hazard ratio [HR] = 1.786; 95% confidence interval [CI]: 1.272-2.509; p = 0.001) and absence of POCT (HR = 2.841; 95% CI: 2.159-3.738; p < 0.001) were independent prognostic risk factors, while primary tumour locations in the meninges (HR = 0.136; 95% CI: 0.032-0.569; p = 0.006) and other nervous system regions (HR = 0.552; 95% CI: 0.326-0.936; p = 0.027), as well as histological morphologies such as diffuse large B-cell lymphoma (HR = 0.233; 95% CI: 0.128-0.425; p < 0.001) and non-Hodgkin lymphoma (HR = 0.559; 95% CI: 0.356-0.876; p = 0.011), were associated with favourable patient outcomes. K-M curves demonstrated that the group undergoing POCT had a significantly more favourable prognosis compared to the non-POCT group, before (HR = 0.454; 95% CI: 0.343-0.600; p < 0.0001) or after PSM (HR = 0.580; 95% CI: 0.431-0.780; p < 0.0001). For patients with PCNSL, those with tumours located in the infratentorial region (HR = 0.231; 95% CI: 0.078-0.682; p = 0.046), supratentorial region (HR = 0.250; 95% CI: 0.163-0.383; p < 0.0001), overlapping brain regions (HR = 0.201; 95% CI: 0.056-0.727; p = 0.0058), and those who underwent biopsy (HR = 0.740; 95% CI: 0.463-1.182; p = 0.003), subtotal resection (STR) (HR = 0.490; 95% CI: 0.265-0.906; p = 0.0064), or gross total resection (GTR) (HR = 0.613; 95% CI: 0.292-1.287; p = 0.0003) had better prognoses in the postoperative chemotherapy group compared to the non-chemotherapy group. Conclusion POCT significantly improves the prognosis of PCNSL patients and identifies the characteristics of the benefiting population. This information aids clinical practitioners in designing personalized treatment plans for individuals and advancing precise treatment.
Assuntos
Neoplasias do Sistema Nervoso Central , Programa de SEER , Humanos , Feminino , Masculino , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/cirurgia , Pessoa de Meia-Idade , Idoso , Prognóstico , Linfoma/mortalidade , Linfoma/terapia , Linfoma/tratamento farmacológico , Linfoma/patologia , Adulto , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Quimioterapia Adjuvante , Pontuação de PropensãoRESUMO
The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.
Assuntos
Carcinoma de Células Escamosas , Histerectomia , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Terapia Combinada , Histerectomia/métodos , Excisão de Linfonodo , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies. METHODS: On-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto). BC quantity, tumor-infiltrating lymphocytes (TILs), and the proliferation marker Ki-67 were compared to pre-treatment samples. The study investigated the correlation between residual cancer, changes in Ki-67 and TILs, and their impact on pathologic complete response (pCR) and disease-free survival (DFS). RESULTS: Among the 297 samples, 138 (46%) were hormone receptor-positive (HR+)/human epidermal growth factor 2-negative (HER2-), 87 (29%) were triple-negative (TNBC), and 72 (24%) were HER2+. Invasive tumor cells were found in 70% of on-treatment biopsies, with varying rates across subtypes (HR+/HER2-: 84%, TNBC: 62%, HER2+: 51%; p < 0.001). Patients with residual tumor on-treatment had an 8% pCR rate post-treatment (HR+/HER2-: 3%, TNBC: 19%, HER2+: 11%), while those without any invasive tumor had a 50% pCR rate (HR+/HER2-: 27%; TNBC: 48%, HER2+: 66%). Sensitivity for predicting residual disease was 0.81, with positive and negative predictive values of 0.92 and 0.50, respectively. Increasing TILs from baseline to on-treatment biopsy (if residual tumor was present) were linked to higher pCR likelihood in the overall cohort (OR 1.034, 95% CI 1.013-1.056 per % increase; p = 0.001) and with a longer DFS in TNBC (HR 0.980, 95% CI 0.963-0.997 per % increase; p = 0.026). Persisting or increased Ki-67 was associated with with lower pCR probability in the overall cohort (OR 0.957, 95% CI 0.928-0.986; p = 0.004) and shorter DFS in TNBC (HR 1.023, 95% CI 1.001-1.047; p = 0.04). CONCLUSION: On-treatment biopsies can predict patients unlikely to achieve pCR post-therapy. This could facilitate therapy adjustments for TNBC or HER2 + BC. They also might offer insights into therapy resistance mechanisms. Future research should explore whether standardized or expanded sampling enhances the accuracy of on-treatment biopsy procedures. Trial registration GeparQuattro (EudraCT 2005-001546-17), GeparQuinto (EudraCT 2006-005834-19) and GeparSixto (EudraCT 2011-000553-23).
Assuntos
Neoplasias da Mama , Linfócitos do Interstício Tumoral , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Terapia Neoadjuvante/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Biópsia , Adulto , Receptor ErbB-2/metabolismo , Antígeno Ki-67/metabolismo , Idoso , Resultado do Tratamento , Biomarcadores Tumorais/metabolismo , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia Residual/patologia , Intervalo Livre de Doença , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Quimioterapia Adjuvante/métodosRESUMO
PURPOSE: To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. METHODS: This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. RESULTS: In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). CONCLUSIONS: In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.
Assuntos
Dexametasona , Retinopatia Diabética , Implantes de Medicamento , Glucocorticoides , Injeções Intravítreas , Edema Macular , Ranibizumab , Acuidade Visual , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Dexametasona/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/complicações , Masculino , Estudos Retrospectivos , Feminino , Ranibizumab/administração & dosagem , Pessoa de Meia-Idade , Resultado do Tratamento , Glucocorticoides/administração & dosagem , Idoso , Inibidores da Angiogênese/administração & dosagem , Quimioterapia Adjuvante , Fatores de Tempo , Tomografia de Coerência Óptica , Substituição de MedicamentosAssuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Recidiva Local de Neoplasia , Nefrectomia , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Quimioterapia Adjuvante , Antineoplásicos Imunológicos/uso terapêutico , Taxa de SobrevidaRESUMO
BACKGROUND/AIM: Although perioperative chemotherapy has improved patient survival, sarcopenia may occur during chemotherapy owing to decreased food intake and physical strength. However, reports on the occurrence of sarcopenia and changes in body composition in patients with pancreatic cancer during neoadjuvant chemotherapy are scarce. This study aimed to determine the effect of changes in skeletal muscle mass during neoadjuvant chemotherapy on the S-1 adjuvant chemotherapy clinical course in patients who underwent perioperative chemotherapy and surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 159 patients with pancreatic cancer who underwent neoadjuvant chemotherapy and surgical resection, followed by S-1 adjuvant chemotherapy. We evaluated changes in skeletal muscle mass during neoadjuvant chemotherapy using abdominal computed tomography and the SliceOmatic software. The association between the rate of change in skeletal muscle mass index (Δ%SMI) during neoadjuvant chemotherapy and the continuation of S-1 adjuvant chemotherapy was investigated. RESULTS: Eighty-eight (55.3%) patients lost skeletal muscle mass (Δ%SMI <0) during neoadjuvant chemotherapy with a significantly low S-1 adjuvant completion rate (p=0.02). Δ%SMI <0 was an independent risk factor for the continuation of S-1 adjuvant chemotherapy (hazard ratio=1.924, 95% confidence interval=1.002-3.695, p=0.049). Moreover, the lower the Δ%SMI, the lower the S-1 continuation rate (p=0.022). CONCLUSION: Loss of skeletal muscle mass during neoadjuvant chemotherapy for pancreatic cancer affected the continuation of S-1 adjuvant chemotherapy after pancreatic resection. Therefore, ameliorating loss of skeletal muscle mass during neoadjuvant chemotherapy should be carefully considered to improve the continuation rate of adjuvant chemotherapy and the survival of patients with pancreatic cancer.
Assuntos
Combinação de Medicamentos , Músculo Esquelético , Terapia Neoadjuvante , Ácido Oxônico , Pancreatectomia , Neoplasias Pancreáticas , Sarcopenia , Tegafur , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Masculino , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Feminino , Terapia Neoadjuvante/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Pancreatectomia/efeitos adversos , Estudos Retrospectivos , Sarcopenia/induzido quimicamente , Sarcopenia/etiologia , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , AdultoRESUMO
BACKGROUND: Extensive surgery on advanced-stage epithelial ovarian cancer is associated with increased postoperative morbidity, which may cause a delay in or omission of chemotherapy. We examined postoperative complications and their effects on adjuvant treatment in patients undergoing primary debulking surgery (PDS). METHODS: Stage IIIC-IV epithelial ovarian cancer patients who underwent PDS between January 2013 and December 2020 were included. Patients were divided into two groups according to the radicality of the operation, i.e., extensive or standard surgery, and their outcomes were compared. RESULTS: In total, 172 patients were included; 119 underwent extensive surgery, and 53 had standard surgery. Clavien-Dindo grade 3-5 (CDC 3+) complications were detected in 41.2% of patients after extensive operations and in 17% after standard surgery (p = 0.002). The most common CDC 3+ complication was pleural effusion. Despite the difference in the complication rates, the delay in chemotherapy did not differ between the extensive and standard groups (p = 0.98). CONCLUSIONS: Complications are common after PDS. Extensive surgery increases the complication rate, but most complications can be treated effectively; therefore, a delay in adjuvant treatment is rare.
Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Complicações Pós-Operatórias , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Idoso , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Adulto , Estudos Retrospectivos , Tempo para o Tratamento/estatística & dados numéricosRESUMO
BACKGROUND: The primary treatment approach for addressing low-risk nonmetastatic gestational trophoblastic neoplasia (LR-NMGTN) in women desiring fertility preservation involves chemotherapy. An alternative option for treatment is fertility-sparing surgical interventions, either alone or in combination with adjuvant chemotherapy. The hypothesised advantages of choosing fertility-sparing surgery in cases of LR-NMGTN include potential avoidance of adverse effects associated with chemotherapy, potential reduction in the number of chemotherapy cycles required to achieve complete remission, and potential reduction in time to remission. OBJECTIVES: To measure the benefits and harms of fertility-sparing surgical interventions, with or without adjuvant chemotherapy, compared to primary chemotherapy alone, for the treatment of women with low-risk, non-metastatic gestational trophoblastic neoplasia (LR-NMGTN). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov and WHO ICTRP on 31 January 2024. We also searched abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing fertility-sparing surgical interventions, with or without subsequent adjuvant chemotherapy, versus primary chemotherapy as standard care for the treatment of women with LR-NMGTN. DATA COLLECTION AND ANALYSIS: We employed standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of evidence for each outcome, if available. We focused on the following outcomes: treatment success rate, relapse, disease-specific mortality, death due to treatment, pregnancy rate, quality of life, and any adverse events. MAIN RESULTS: We included two RCTs, with a total of 151 participants contributing data to our analyses. Both studies used uterine curettage as the fertility-sparing surgical intervention. Fertility-sparing surgical intervention without subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 62 participants with varying hCG (human chorionic gonadotrophin) levels evaluated this comparison. Most of our outcomes of interest were not measured in this study. The relative risk of experiencing any adverse event could not be estimated as chemotherapy adverse effects were not reported. The study reported that there were no surgical complications. Chemotherapy was administered to 50% of participants in the intervention group after curettage because their hCG levels increased. Fertility-sparing surgical intervention with subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 89 participants with hCG levels < 5000 IU/L evaluated this comparison. We judged the risk of bias in the study to be high. The evidence was very uncertain about the effect of uterine curettage with subsequent adjuvant chemotherapy on treatment success rate (RR 1.03, 95% CI 0.86 to1.23; 86 participants), relapse (RR 0.5, 95% CI 0.05 to 5.31; 86 participants), pregnancy rate (RR 0.86, 95% CI 0.31 to 2.34; 86 participants), and rate of adverse events (RR 1.15, 95% CI 0.63 to 2.13; 86 participants), all very low certainty evidence. The relative risks of disease-specific mortality and death due to treatment could not be estimated as there were no deaths in either group. There were no results for quality of life as this outcome was not reported. AUTHORS' CONCLUSIONS: Uterine curettage is the only fertility-sparing surgical intervention for LR-NMGTN that has been evaluated in a randomised controlled trial. The evidence is very uncertain about the benefits and harms of uterine curettage, with or without subsequent adjuvant chemotherapy, compared to primary chemotherapy alone. The two available studies are small with a high risk of bias, and future research may find substantially different results for all reported outcomes. Larger RCTs, with appropriate clinical outcome measures, would be required to determine the benefits or harms of fertility-sparing surgical interventions for this population.
Assuntos
Preservação da Fertilidade , Doença Trofoblástica Gestacional , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Feminino , Gravidez , Doença Trofoblástica Gestacional/cirurgia , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/mortalidade , Preservação da Fertilidade/métodos , Quimioterapia Adjuvante , Taxa de Gravidez , Recidiva Local de Neoplasia/prevenção & controle , Qualidade de VidaRESUMO
BACKGROUND: Studies on several malignancies have suggested that the time to commencement of adjuvant chemotherapy (AC) is associated with survival outcomes. There have, however, been no relevant reports of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: This clinical study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was progression-free survival (PFS). Inverse probability of treatment weighting was used to control for confounding factors. Cox models with restricted cubic splines, Kaplan-Meier method and log-rank tests were used to evaluate the relationship between AC timing and survival. RESULTS: A total of 551 patients were identified [median age, 45 years (interquartile range 36-52 years); 383 (69.5%) male]. Restricted cubic splines demonstrated that the timing of AC initiation had a U-shaped association with PFS. The risk of disease progression decreased within 37 days and subsequently increased. From 37 to 90 days, each additional 7-day delay conferred worse PFS of 1.32 months {hazard ratio (HR): 1.14 [95% confidence interval (CI) 1.01-1.28], P = 0.04}. The cut-off value of the receiver operating characteristic curve for initiation was 69.5 days. At a median follow-up of 48 months, the PFS was significantly better in patients initiated within 69.5 days [HR: 2.18 (95% CI 1.17-4.06), log-rank P = 0.009], with a higher 3-year rate [78.8% (95% CI 75.1% to 82.7%) versus 59.0% (95% CI 42.2% to 82.5%)] than beyond 69.5 days. Positive results were also observed in secondary endpoints. The initiation group was an independent prognostic factor [HR: 2.28 (95% CI 1.42-3.66), P < 0.001]. CONCLUSIONS: The optimal timing of AC initiation is â¼37 days after concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. A delay beyond 69.5 days is associated with compromised survival. Efforts should be made to address the reasons for delays and ensure the timely initiation of AC.
Assuntos
Quimiorradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Feminino , Adulto , Quimioterapia Adjuvante/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Quimiorradioterapia/métodos , Fatores de Tempo , Estudos RetrospectivosRESUMO
BACKGROUND: Randomised controlled trials (RCTs) reported adjuvant trastuzumab-based treatment improved overall survival (OS) among patients with HER2-positive early invasive breast cancer (EIBC). Few RCTs included older patients or those with comorbidity/frailty. This study aimed to determine whether the effect of adjuvant trastuzumab-based treatment on survival outcomes varies by patient age and fitness, using national data from routine care. METHODS: Women (50+ years) newly-diagnosed with HER2-positive EIBC between 2014 and 2019 were identified from England Cancer Registry data. Registration records were linked to Systemic Anti-Cancer Therapy data for treatment details and ONS death register for mortality details. A propensity score analysis employing the inverse probability of treatment weighting method was used to balance the patient variables across treatment groups. Cox models were used to evaluate whether the effect of treatment on OS was associated with patient age and fitness; competing risks regression models were used for breast cancer-specific survival (BCSS). RESULTS: 5238 women initiated adjuvant trastuzumab-based treatment. Median follow-up was 56.7 months. Comparison with 3421 women who did not receive adjuvant trastuzumab highlighted differences at diagnosis in relation to age, fitness, grade, nodal involvement, surgery type and use of radiotherapy. Weighted survival analysis found trastuzumab was associated with improved OS (hazard ratio HR 0.56, 95 %CI: 0.45-0.70) and improved BCSS (subHR 0.62, 95 %CI: 0.47-0.82). We found no evidence of a difference in effect by age or patient fitness for either outcome. CONCLUSION: In this national dataset, adjuvant trastuzumab was associated with improvements in survival, with an OS effect size similar to RCT evidence. The effect size was not found to vary by patient age or fitness. Chronological age and fitness alone should not be barriers to receipt of effective adjuvant targeted treatment.