Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis / 中华外科杂志

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer / 北京大学学报(医学版)

OBJECTIVE@#To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC).@*METHODS@#From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed.@*RESULTS@#Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range.@*CONCLUSION@#This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Which Tyrosine Kinase Inhibitor Must We Apply Before? A Case Report of Crizotinib-resistant Patient with Concomitant EGFR and EML4-ALK Gene Mutations

ABSTRACT The concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocations in lung adenocancers are very rare scenarios. Until now, 42 cases described in the literature have all been treated by different drugs. There is no overall consensus regarding the treatment for this adenocarcinoma subgroup. We report here a case of lung adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in primary tumour, EGFR mutation in exon 21 (L858R) and no ALK rearrangement in its synchronous metastasis. We treated this patient with crizotinib as the second-line therapy (after the first line docetaxel-cisplatin chemotherapy), but no response was obtained. The therapeutic choice for the lung adenocancer patients with concomitant EGFR mutation and ALK rearrangement is unclear. Examination of c-ros oncogene 1 mutation can be used as an indicator in the prediction of the crizotinib treatment success. The ALK mutation may not responsible for the resistance to EGFR-tyrosine kinase inhibitors (TKI), and EGFR-TKI can be initiated to EGFR and ALK dual mutant patients as the first treatment.

Cost-effectiveness analysis of abiraterone, docetaxel or placebo plus androgen deprivation therapy for hormone-sensitive advanced prostate cancer / Análise de custo-efetividade da adição de abiraterona ou quimioterapia ao tratamento do câncer de próstata metastático hormônio-sensível

ABSTRACT Objective To evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to androgen deprivation. Methods We developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus androgen deprivation therapy alone. Direct and indirect costs were included in the model. The effects were expressed in Quality-Adjusted Life Years adjusted for side effects. Results Compared to androgen deprivation therapy alone, the addition of chemotherapy and of abiraterone generated 0.492 and 0.999, respectively, in Quality-Adjusted Life Years. Abiraterone led to a Quality-Adjusted Life Years gain of 0.506 compared to docetaxel. The incremental costs per Quality-Adjusted Life Years were R$ 133.649,22 for docetaxel, R$ 330.828,70 for abiraterone and R$ 571.379,42 for abiraterone compared to docetaxel, respectively. Conclusion The addition of chemotherapy to androgen deprivation therapy is more cost-effective than the addition of abiraterone to androgen deprivation therapy. However, discounts on abiraterone cost might improve cost-effectiveness.

RESUMO Objetivo Avaliar a relação custo-efetividade da adição de quimioterapia ou abiraterona à terapia de privação hormonal. Métodos Um modelo analítico foi desenvolvido para determinar a relação custo-efetividade da adição de docetaxel ou abiraterona comparada à terapia de privação hormonal isolada. Custos diretos e indiretos foram incluídos no modelo. Os efeitos foram expressos em Anos de Vida Ajustados para Qualidade corrigidos pelos efeitos colaterais de cada terapia. Resultados A adição de quimioterapia e de abiraterona à terapia de privação hormonal aumentou os Anos de Vida Ajustados para Qualidade em 0,492 e 0,999, respectivamente, em comparação à terapia de privação hormonal isolada. A abiraterona promoveu ganho de Anos de Vida Ajustados para Qualidade de 0,506 em relação ao docetaxel. O custo incremental por Anos de Vida Ajustados para Qualidade foi R$ 133.649,22 para o docetaxel, R$ 330.828,70 para a abiraterona e R$ 571.379,42 para a abiraterona comparada ao docetaxel. Conclusão A adição de quimioterapia à terapia de privação hormonal é mais custo-efetiva que a adição de abiraterona à terapia de privação hormonal. Contudo, descontos no custo da abiraterona poderiam tornar esse tratamento mais custo-efetivo.

Evolução Clínica e Preditores da Neuropatia Periférica Induzida por Quimioterapia / Clinical Evolution and Predictors of Chemotherapy-Induced Peripheral Neuropathy / Evolución Clínica y Predictores de la Neuropatía Periférica Inducida por Quimioterapia

Introdução: Drogas antineoplásicas neurotóxicas estão frequentemente associadas à neuropatia periférica induzida por quimioterapia (NPIQ). Objetivo: Avaliar a evolução clínica dos pacientes expostos a tratamento antineoplásico potencialmente neurotóxico e identificar possíveis preditores clínicos e sociodemográficos para o desenvolvimento da NPIQ. Método: Estudo de coorte prospectiva com pacientes com diagnóstico de câncer de mama, ovário ou intestino em tratamento quimioterápico com paclitaxel, docetaxel ou oxaliplatina. Foram avaliados antes da quimioterapia (T1), no terceiro mês (T2) e 30-60 dias após interrupção do tratamento (T3). Todos responderam ao questionário de perfis sociodemográfico e clínico, foram avaliados por meio de exame clínico neurológico, pela escala de performance ECOG, escala hospitalar de ansiedade e depressão (HAD), escala de dor Short-cGuill, autorrelato de sintomas de NPIQ e avaliação com o questionário de neurotoxicidade induzida por antineoplásicos (CINQ). Resultados: Por meio de autorrelato, 75% da dos pacientes informaram apresentar sintomas de NPIQ. O CINQ evidenciou que 90% apresentaram algum grau de NPIQ em T2, enquanto 82,5% ainda persistiam em T3. Dor neuropática acometeu 42% da população (RR=1,429; IC95%=1,130-1,806). Os escores de ansiedade e depressão reduziram significativamente quando comparados ao início de tratamento (redução de 2,5 pontos na escala HAD, p<0,05). A capacidade funcional da população não mostrou alterações significativas. No T2, a escolaridade foi considerada preditora para autorrelato de sintomas de NPIQ (OR=1,314, IC95%=1,002-1,723, p=0,048). Conclusão:A baixa escolaridade pode comprometer a capacidade do paciente em relatar os sintomas da NPIQ. Este estudo chama a atenção para a necessidade de utilização de instrumentos específicos para detecção precoce da NPIQ.

Introduction: Neurotoxic antineoplastic drugs are frequently associated to chemotherapy-induced peripheral neuropathy (CIPN). Objective: To evaluate the clinical evolution of patients exposed to potentially neurotoxic antineoplastic treatment and to identify possible clinical and sociodemographic predictors for the development of CIPN. Method: Cohort prospective study with patients with breast, ovary or intestine diagnosis of cancer in chemotherapy treatment with paclitaxel, docetaxel or oxaliplatin. They were assessed before the chemotherapy (T1), in the third month (T2) and 30-60 days after the interruption of the treatment (T3). All the patients responded to the questionnaire of clinical and sociodemographic profiles, were evaluated through neurologic clinical exam, by the performance scale ECOG, by the Hospital Anxiety and Depression Scale - HAD, pain scale of Short-cGuill, self-report of symptoms of CIPN and evaluation with the questionnaire of antineoplastic-induced neurotoxicity (QAIN). Results: Through self-report, 75% of the patients presented symptoms of CIPN. The QAIN showed that 90% presented a certain degree of CIPN in T2, while 82.5% still persisted in T3. Neuropathic pain affected 42% of the population (RR = 1.429, CI95% = 1.130-1.806). Anxiety and depression scores significantly reduced when compared with the beginning of the treatment (reduction of 2.5 points in the scale HAD, p < 0.05). The functional capacity of the population did not show any significant change. The school level was considered a predictor of self-report of CIPN symptoms in T2 (OR = 1.314, CI95% = 1.002-1.723, p = 0.048). Conclusion: The low school level may taint the patient capacity to report CIPN symptoms. This study draws attention for the necessity to use specific instruments for early detection of CIPN.

Introducción: Los fármacos antineoplásicos neurotóxicos a menudo se asocian con neuropatía periférica inducida por quimioterapia (CIPN). Objetivo: Evaluar la evolución clínica de pacientes expuestos a tratamientos antineoplásicos potencialmente neurotóxicos e identificar posibles predictores clínicos y sociodemográficos para el desarrollo de CIPN. Método: Estudio de cohorte prospectivo con pacientes diagnosticadas con cáncer de mama, ovario o intestino sometidos a quimioterapia con paclitaxel, docetaxel u oxaliplatino. Se evaluaron antes de la quimioterapia (T1), en el tercer mes (T2) y 30-60 días después de la interrupción del tratamiento (T3). Todos respondieron el cuestionario de perfil sociodemográfico y clínico, se evaluaron mediante un examen neurológico clínico, la escala de rendimiento ECOG, la escala de ansiedad y depresión hospitalaria (HAD), la escala de dolor Short-cGuill, el autoinforme de los síntomas de CIPN y la evaluación con el cuestionario de neurotoxicidad inducida por antineoplásicos (CINQ). Resultados: Por autoinforme, el 75% de la población informó presentar síntomas de CIPN. El CINQ mostró que el 90% tenía algún grado de NPIQ en T2, mientras que el 82.5% aún persistía en T3. El dolor neuropático afectó al 42% de la población (RR = 1.429; IC del 95% = 1.130-1.806). Las puntuaciones de ansiedad y depresión disminuyeron significativamente en comparación con el valor inicial (reducción de 2.5 puntos HAD, p <0.05). La capacidad funcional de la población no mostró cambios significativos. En T2, la educación se consideró un predictor de síntomas CIPN autoinformados (OR=1.314, IC 95%=1.002-1.723, p=0,048). Conclusión: La baja educación puede comprometer la capacidad del paciente para informar los síntomas de CIPN. Este estudio llama la atención sobre la necesidad de utilizar instrumentos específicos para la detección temprana de CIPN.

The transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines / 亚洲男科学杂志(英文版)

One of the factors promoting tumoral progress is the abnormal activation of the epithelial-mesenchymal transition (EMT) program which has been associated with chemoresistance in tumoral cells. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), a key EMT activator, has recently been related to docetaxel resistance, the main chemotherapeutic used in advanced prostate cancer treatment. The mechanisms involved in this protective effect are still unclear. In a previous work, we demonstrated that ZEB1 expression induced an EMT-like phenotype in prostate cancer cell lines. In this work, we used prostate cancer cell lines 22Rv1 and DU145 to study the effect of ZEB1 modulation on docetaxel resistance and its possible mechanisms. The results showed that ZEB1 overexpression conferred to 22Rv1 cell resistance to docetaxel while its silencing made DU145 cells more sensitive to it. Analysis of resistance markers showed no presence of ATP-binding cassette subfamily B member 1 (MDR1) and no changes in breast cancer resistance protein (BCRP) or ATP-binding cassette subfamily C member 10 (MRP7). However, a correlation between ZEB1, multidrug resistance-associated protein 1 (MRP1), and ATP-binding cassette subfamily C member 4 (MRP4) expression was observed. MRP4 inhibition, using MK571, resensitized cells with ZEB1 overexpression to docetaxel treatment. In addition, modulation of ZEB1 and subsequent change in MRP4 expression correlated with a lower apoptotic response to docetaxel, characterized by lower B-cell lymphoma 2 (Bcl2), high BCL2-associated X protein (Bax), and high active caspase 3 expression. The response to docetaxel in our model seems to be mediated mainly by activation of the apoptotic death program. Our results showed that modulation of MRP4 could be a mediator of ZEB1-related resistance to docetaxel in prostate cancer, making it a possible marker for chemotherapy response in patients who do not express MDR1.

Role of chemotherapy in prostate cancer / 亚洲男科学杂志(英文版)

Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen (PSA) and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China / 亚洲男科学杂志(英文版)

Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.