Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer.

BACKGROUND: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking. METHODS: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety. RESULTS: In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed. CONCLUSIONS: Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.).

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).

The Mechanisms of Current Platinum Anticancer Drug Resistance in the Glioma.

Gliomas are the most common and malignant primary tumors of the central nervous system (CNS). Glioblastomas are the most malignant and aggressive form of primary brain tumors and account for the majority of brain tumor-related deaths. The current standard treatment for gliomas is surgical resection supplemented by postoperative chemotherapy. Platinum drugs are a class of chemotherapeutic drugs that affect the cell cycle, and the main site of action is the DNA of cells, which are common chemotherapeutic drugs in clinical practice. Chemotherapy with platinum drugs such as cisplatin, carboplatin, oxaliplatin, or a combination thereof is used to treat a variety of tumors. However, the results of gliomas chemotherapy are unsatisfactory, and resistance to platinum drugs is one of the important reasons. The resistance of gliomas to platinum drugs is the result of a combination of influencing factors. Decreased intracellular drug concentration, enhanced function of cell processing active products, enhanced repair ability of cellular DNA damage, and blockage of related apoptosis pathways play an important role in it. It is known that the pathogenic properties of glioma cells and the response of glioma towards platinum-based drugs are strongly influenced by non-coding RNAs, particularly, by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs and lncRNAs control drug sensitivity and the development of tumor resistance towards platinum drugs. This mini-review summarizes the resistance mechanisms of gliomas to platinum drugs, as well as molecules and therapies that can improve the sensitivity of gliomas to platinum drugs.

Effect of kangai injection combined with platinum-based chemotherapy on the immune function of patients with advanced non-small-cell lung cancer: A meta-analysis.

BACKGROUND: Kangai injection (KAI) is a well-known Chinese patent medicine applied for several different types of cancers in the clinic as an auxiliary therapeutic approach, which is refined from three herbal extracts (Astragalus, Ginseng and Matrine). PURPOSE: To systematically evaluate the effect of combination treatment of platinum-based chemotherapy and KAI on patients with advanced non-small-cell lung cancer (NSCLC). STUDY DESIGN: A meta-analysis of randomized clinical trials. MATERIALS AND METHODS: The randomized controlled trials (RCTs) about stage Ⅲ-Ⅳ NSCLC using KAI combined platinum-based chemotherapy were electronically retrieved from eight electronic databases up to July 2021. We applied RevMan 5.4, Stata 16.0, TSA 0.9.5.10 Beta and GRADE Pro-GDT to evaluate the quality of the included RCTs and perform the meta-analysis. RESULTS: 19 RCTs were included, consisting a total sample size of 1,389 cases. Meta-analysis revealed that compared with chemotherapy alone, KAI combined with platinum-based chemotherapy was associated with significantly higher objective response rate (ORR) [RR = 1.36, 95%CI (1.21,1.54), p< 0.00001], higher disease control rate (DCR) [RR = 1.15, 95%CI (1.09,1.21), p< 0.00001], greater Karnofsky performance status (KPS) [RR = 1.75, 95%CI (1.41,2.18), p< 0.00001], lower white blood cell toxicity [RR = 0.67, 95%CI (0.55,0.82), p = 0.0001], lower platelet toxicity [RR = 0.60, 95%CI (0.47,0.75), P  < 0.0001], and lower incidence of vomiting [RR = 0.66, 95%CI (0.57,0.76), p< 0.00001]. In terms of the immune function, KAI united with chemotherapy significantly raised the ratio of CD3+ cells [MD = 10.65, 95%CI (8.21,13.09), p< 0.00001], CD4+ cells [MD = 7.67, 95%CI (6.31,9.03), p< 0.00001], NK cells [MD = 4.97, 95%CI (3.03,6.92), p< 0.00001], and CD4+/ CD8+ [MD = 0.32, 95%CI (0.19,0.45), p< 0.00001], and decreased the percentage of CD8+ cells [MD = -5.56, 95%CI (-7.51,-3.61), p< 0.00001]. CONCLUSIONS: This meta-analysis identified that the combination treatment of KAI and platinum-based chemotherapy was more beneficial to patients with advanced NSCLC when compared to chemotherapy alone, which could significantly improve the clinical efficacy, enhance the immune function, and reduce chemotherapy toxicity. Our study provides a theoretical basis and treatment guidance for patients with NSCLC.

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings. METHODS: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients. RESULTS: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. CONCLUSIONS: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

Potential efficacy of weekly low-dose administration of bevacizumab as a combination therapy for platinum-resistant ovarian carcinoma: a retrospective analysis.

BACKGROUND: Bevacizumab (Bev) plays the central role of the adjuvant therapy for patients with ovarian carcinoma. The aim of our study was to examine whether differences in the administration of Bev influence the prognosis of patients. METHODS: Patients with ovarian carcinoma who received treatment at two hospitals between 1999 and 2020 were identified. Patients treated with weekly low-dose administration of Bev (100 mg Bev on days 1 and 8 and 200 mg Bev on day 15, monthly) at one hospital (group A) and those with monthly high-dose administration of Bev (15 mg/kg of Bev on day 1, monthly) at another hospital (group B) were retrospectively compared. RESULTS: Among the total patients, 44 were assigned to group A and 33 were assigned to group B. More patients in group A had advanced disease (p = 0.03) and a lower dose of Bev at the first time during the first cycle administration (p < 0.01) than in group B. Progression-free survival (PFS) was better in group A than in group B (p < 0.01). Multivariate analysis revealed that group A was a better prognostic factor for PFS (hazard ratio 0.53, p = 0.03). Stable duration was longer in group A than in group B (p < 0.01). The incidences of adverse effects, including hematological toxicities such as neutropenia (p = 0.01) and nonhematological toxicities such as hypertension (p < 0.01), intestinal obstruction (p < 0.01), and thromboembolic events (p < 0.01), were lower in group A than in group B. CONCLUSIONS: Weekly low-dose administration of Bev might improve prognosis and decrease the frequency of adverse effects associated with this drug although the prospective study was needed to get corroboration.

[The prospects of DNA damage repair variants guiding platinum compounds in the treatment of triple negative breast cancer].

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.

Platinum-based adjuvant chemotherapy for upper tract urothelial carcinoma: a change of paradigm? A meta-analysis of aggregate data.

We performed a systematic review and meta-analysis to evaluate the role of platinum-based adjuvant chemotherapy (AC) in upper tract urothelial carcinoma. Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Outcomes of interest included: overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Platinum-based AC was associated with improved DFS, while the benefit in OS and CSS was not statistically significant compared to observation. Conversely, platinum-based AC showed a modest OS benefit in an analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. Our results suggest that platinum-based AC is associated with improved DFS and a modest OS benefit in patients with locally advanced urothelial carcinomas.

The prospects of DNA damage repair variants guiding platinum compounds in the treatment of triple negative breast cancer / 中华肿瘤杂志

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.

Clinical efficacy and safety of Huachansu injection combination with platinum-based chemotherapy for advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy. OBJECTIVE: To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence. RESULTS: A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia. CONCLUSIONS: Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.

Artificial intelligence-based image analysis can predict outcome in high-grade serous carcinoma via histology alone.

High-grade extrauterine serous carcinoma (HGSC) is an aggressive tumor with high rates of recurrence, frequent chemotherapy resistance, and overall 5-year survival of less than 50%. Beyond determining and confirming the diagnosis itself, pathologist review of histologic slides provides no prognostic or predictive information, which is in sharp contrast to almost all other carcinoma types. Deep-learning based image analysis has recently been able to predict outcome and/or identify morphology-based representations of underlying molecular alterations in other tumor types, such as colorectal carcinoma, lung carcinoma, breast carcinoma, and melanoma. Using a carefully stratified HGSC patient cohort consisting of women (n = 30) with similar presentations who experienced very different treatment responses (platinum free intervals of either ≤ 6 months or ≥ 18 months), we used whole slide images (WSI, n = 205) to train a convolutional neural network. The neural network was trained, in three steps, to identify morphologic regions (digital biomarkers) that are highly associating with one or the other treatment response group. We tested the classifier using a separate 22 slide test set, and 18/22 slides were correctly classified. We show that a neural network based approach can discriminate extremes in patient response to primary platinum-based chemotherapy with high sensitivity (73%) and specificity (91%). These proof-of-concept results are novel, because for the first time, prospective prognostic information is identified specifically within HGSC tumor morphology.

Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management.

Resistance to platinum-based chemotherapy is a major clinical challenge in ovarian cancer, contributing to the high mortality-to-incidence ratio. Management of the platinum-resistant disease has been difficult due to diverse underlying molecular mechanisms. Over the past several years, research has revealed several novel molecular targets that are being explored as biomarkers for treatment planning and monitoring of response. The therapeutic landscape of ovarian cancer is also rapidly evolving, and alternative therapies are becoming available for the recurrent platinum-resistant disease. This review provides a snapshot of platinum resistance mechanisms and discusses liquid-based biomarkers and their potential utility in effective management of platinum-resistant ovarian cancer.

Incorporating SULF1 polymorphisms in a pretreatment CT-based radiomic model for predicting platinum resistance in ovarian cancer treatment.

OBJECTIVE: Early detection of platinum resistance for ovarian cancer treatment remains challenging. This study aims to develop a machine learning model incorporating genomic data such as Single-Nucleotide Polymorphisms (SNPs) of Human Sulfatase 1 (SULF1) with a CT radiomic model based on pre-treatment CT images, to predict platinum resistance for ovarian cancer (OC) treatment. METHODS: A cohort of 102 patients with pathologically confirmed OC was retrospectively enrolled into this study from January 2006 to February 2018. All patients had platinum-based chemotherapy after maximal cyto-reductive surgery. This cohort was separated into two groups according to treatment response, i.e., the group with platinum-resistant disease (PR group) and the group with platinum-sensitive disease (PS group). We genotyped 12 SNPs of SULF1 for all OC patients using Mass Array Method. Radiomic features, SNP data and clinicopathological data of the 102 patients were used to build the differentiation models. The study participants were divided into two cohorts: the training cohort (n = 71) and the validation cohort (n = 31). Feature selection and predictive modeling were performed using least absolute shrinkage and selection operator (LASSO), Random Forest Classifier and Support Vector Machine methods. Model performance for predicting platinum resistance was assessed with respect to its calibration, discrimination, and clinical application. RESULTS: For prediction of platinum resistance, the approach combining the radiomics, clinicopathological data and SNP data demonstrated higher classification efficiency, with an AUC value of 0.993 (95 % CI: 0.83 to 0.98) in the training cohort and 0.967 (95 % CI: 0.83 to 0.98) in validation cohort, than the performance with only the SNPs of SULF1 model (AUC: training, 0.843 [95 %CI: 0.738-0.948]; validation, 0.815 [0.601-1.000]), or with only the radiomic model (AUC: training, 0.874 [95 %CI: 0.789-0.960]; validation, 0.832 [95 %CI: 0.687-0.976]). This integrated approach also showed good calibration and favorable clinical utility. CONCLUSIONS: A predictive model combining pretreatment CT radiomics with genomic data such as SNPs of SULF1 could potentially help to predict platinum resistance in ovarian cancer treatment.

Manejo e Prevenção de Reações Adversas da Quimioterapia Antineoplásica com Platinas em Pacientes com Cânceres Esofágico e Gástrico: Revisão Sistemática da Literatura / Management and Prevention of Adverse Reactions to Platinum Antineoplastic Chemotherapy in Patients with Esophageal and Gastric Cancer: Systematic Literature Review / Manejo y Prevención de Reacciones Adversas a la Quimioterapia Antineoplásica con Platino en Pacientes con Cánceres de Esófago y Gástrico: Revisión Sistemática de la Literatura

Introdução: O câncer gástrico é a quinta doença maligna mais comum em todo o mundo. Trata-se do tumor maligno mais incidente na Ásia, especialmente na China. O carcinoma esofágico é um dos tipos mais agressivos de tumor maligno. Os tratamentos multimodais, incluindo quimioterapia neoadjuvante e quimiorradioterapia, são utilizados e podem causar fadiga, vômito, diarreia, alterações cutâneas, caquexia e neuropatia periférica, que podem ser efeitos colaterais importantes para muitos pacientes que realizam seus tratamentos. Objetivo: Realizar uma revisão sistemática sobre o manejo e a prevenção de reações adversas da quimioterapia antineoplásica com platinas em pacientes com câncer esofágico e tumor gástrico. Método: Para seleção dos artigos, foi realizada a busca em três bases de dados: MEDLINE/PubMed, Cochrane e Embase, com a estratégia PICO, variando os descritores MeSH/DeCs e operadores booleanos. Resultados: Foram encontrados 455 títulos, dos quais, após utilizar a diretriz PRISMA, restaram 15 artigos para a revisão sistemática, que abordavam o manejo e a prevenção de náusea e vômitos, neuropatia periférica, caquexia, suplementação de magnésio, tratamento de depressão e toxicidade geral. Conclusão: Verificou-se que náuseas, vômitos, neuropatia e hipomagnesemia tiveram maior número de estudos relacionados ao manejo e à prevenção desses sintomas, nos quais identificaram-se algumas sugestões de condutas com maior evidência para essas reações. As demais reações encontradas ainda carecem de mais estudos, principalmente nos casos de cânceres gástrico e esofágico

Introduction: Gastric cancer is the fifth most common malignancy worldwide. It is the most frequent malignant tumor in Asia, especially in China. Esophageal carcinoma is one of the more aggressive types of malignant tumor. Multimodal treatments, including neoadjuvant chemotherapy and chemoradiotherapy are utilized and can cause fatigue, vomiting, diarrhea, skin changes, cachexia, and peripheral neuropathy, which can be important side effects for many patients undergoing their treatments. Objective: Carry out a systematic review on the management and prevention of adverse reactions of antineoplastic chemotherapy with platinum in patients with esophageal cancer and gastric tumor. Method: To select the articles, a search was conducted in three databases: MEDLINE/PubMed, Cochrane and Embase, with the PICO strategy, alternating between MeSH/DeCs descriptors and Boolean operators. Results: 455 titles were found, of which, after using the PRISMA guideline, 15 articles remained for systematic review, addressing the management and prevention of nausea and vomiting, peripheral neuropathy, cachexia, magnesium supplementation, treatment of depression and general toxicity. Conclusion: The greatest number of studies addressing the management and prevention of the symptoms of nausea, vomits, neuropathy and hypomagnesemia were found, and it was possible to identify some suggestions of conducts to treat these reactions. More studies are necessary for the other reactions encountered, mainly in the cases of gastric and esophageal cancer

Introducción: El cáncer gástrico es la quinta neoplasia maligna más común en todo el mundo. Es el tumor maligno más común en Asia, especialmente en China. El carcinoma de esófago es uno de los tipos de tumores malignos más agresivos. Se utilizan tratamientos multimodales, que incluyen quimioterapia neoadyuvante y quimiorradioterapia que pueden provocar: fatiga, vómitos, diarrea, alteraciones cutáneas, caquexia y neuropatía periférica, que pueden ser efectos secundarios importantes para muchos pacientes sometidos a sus tratamientos. Objetivo: Realizar una revisión sistemática sobre el manejo y prevención de reacciones adversas de la quimioterapia antineoplásica con platino en pacientes con cáncer de esófago y tumor gástrico. Método: Para la selección de los artículos se realizó una búsqueda en tres bases de datos: MEDLINE/PubMed, Cochrane y Embase, con la estrategia PICO, variando los descriptores MeSH/DeCs y operadores booleanos. Resultados: Se encontraron 455 títulos, de los cuales, luego de utilizar la guía PRISMA, quedaron 15 artículos para revisión sistemática, que abordaron el manejo y prevención de náuseas y vómitos, neuropatía periférica, caquexia, suplementación con magnesio, tratamiento de la depresión y toxicidad general. Conclusión: Se verifico que náuseas, vómitos, neuropatía e hipomagnesemia tuvieron un mayor número de estudios relacionados con el manejo y prevención de los síntomas, en los cuales fue posible identificar algunas sugerencias de conducta con mayor evidencia de estas reacciones. Las otras reacciones encontradas aún necesitan más estudios, especialmente en casos de cánceres gástrico y de esófago

Rational Design of Near-Infrared-Absorbing Pt(II)-Chelated Azadipyrromethene Dyes as a New Generation of Photosensitizers for Synergistic Phototherapy.

Pt(II) photosensitizers are emerging as novel Pt anticancer agents for cancer photodynamic therapy (PDT) to avoid uncontrollable toxicity of cisplatin. However, the application of Pt(II) photosensitizers is limited by tumor hypoxia and the poor penetration depth of excitation light. To overcome these drawbacks, exploiting the next generation of Pt anticancer agents is of urgent need. According to theoretical calculations, novel near-infrared (NIR)-absorbing Pt(II)-chelated azadipyrromethene dyes (PtDP-X, where X = N, C, and S) were designed. Importantly, spin-orbit coupling of the Pt atom could promote the intersystem crossing of a singlet-to-triplet transition for converting oxygen to singlet oxygen (1O2), and the azadipyrromethene skeleton could provide a strong photothermal effect. As expected, PtDP-X exhibited intense NIR absorption and synergistic PDT and photothermal effects with low dark cytotoxicity. Furthermore, water-soluble and biocompatible PtDP-N nanoparticles (PtDP-N NPs) were prepared that achieved effective tumor cell elimination with low side effects under 730 nm light irradiation in vitro and in vivo. This pioneering work could push the exploitation of NIR-absorbing metal-chelated azadipyrromethene dyes, so as to promote the positive evolution of phototherapy agents.

Platinum versus immunotherapy for unresectable esophageal cancer: A protocol for systematic review and meta analysis.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors, with early metastasis, highly malignant characteristics. Morbidity ranks 7th among all malignant tumors, and mortality ranks 6th. Esophageal adjuvant therapy can significantly improve overall survival in unresectable esophageal cancer patients. With the breakthrough and progress of immunotherapy, the possibility of curing esophageal cancer has greatly increased. Some clinical trials have reported that compared with traditional platinum-based chemotherapy, the use of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors alone can benefit patients and effectively prolong their overall survival. We compare the efficacy of single immunotherapy with traditional platinum-based chemotherapy in a systematic review and meta-analysis to provide a reliable basis for clinicians. METHODS: We will search PubMed, Medline, Embase, Web of Science, Cancerlit, Google Scholar, and the Cochrane Central Register of Controlled Trials for related studies published before December 1, 2019 without language restrictions. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) or quasi-RCTs, and prospective cohort studies will be included. We will perform subgroup analysis in sex, age, ethnicity, and tumor stage of esophageal cancer patients. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for esophageal patients, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity. INPLASY REGISTRATION NUMBER: INPLASY2020110012.

Platinum versus immunotherapy for early resectable non-small cell lung cancer: A protocol for systematic review and meta analysis.

BACKGROUND: Lung cancer is one of the most common malignant tumors. Non-small cell Lung cancer (NSCLC) accounts for about 85% of the total lung cancer. For patients with resectable early NSCLC, conventional postoperative adjuvant therapy can significantly prolong the overall survival of patients and reduce the risk of tumor recurrence. With the emergence and maturity of molecular targeted therapy and immunotherapy, the strategy of postoperative chemotherapy for lung cancer patients has changed greatly. To evaluate the efficacy of postoperative chemotherapy (platinum based chemotherapy and immunotherapy) with or without radiotherapy for NSCLC patients, we will conduct a systematic review and meta-analysis of published or unpublished randomized controlled trials. METHODS: We will search Pubmed (Medline), Embase, Google Scholar, Cancerlit, and the Cochrane Central Register of Controlled Trials for related studies published without language restrictions before June 20, 2021. Two review authors will search and assess relevant studies independently. Randomized controlled trials and quasi-randomized controlled trials studies will be included. we will perform subgroup analysis in different methods of postoperative adjuvant therapy for patients with resectable early NSCLC. Because this study will be based on published or unpublished records and studies, there is no need for ethics approval. INPLASY registration number: INPLASY202080064. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will compare the efficacy of platinum chemotherapy and immunotherapy in patients with resectable early NSCLC. Since the large sample randomized trials that meet the inclusion criteria of this study may be inadequate, we will consider incorporating some high quality small sample related tests, which may lead to heterogeneity and affect the reliability of the results.

Cost-Effectiveness and Net Monetary Benefit of Olaparib Maintenance Therapy Versus No Maintenance Therapy After First-line Platinum-based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-mutated Ovarian Cancer in the Italian National Health Service.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective. METHODS: We developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based chemotherapy to compare cost-effectiveness and net monetary benefit of the 2 strategies. Data on clinical outcomes were obtained from related clinical trial literature and extrapolated using parametric survival analyses. Data on costs were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio (ICUR), and incremental net monetary benefit (INMB) were computed and compared against an incremental cost per quality-adjusted life-year (QALY) gained of €16,372 willingness-to-pay (WTP) threshold. We used deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) to assess how uncertainty affects results; we also performed scenario analyses to compare results under different pricing settings. FINDINGS: In the base-case scenario, during a 50-year time horizon, the total costs for patients treated with olaparib therapy and active surveillance were €124,359 and €97,043, respectively, and QALYs gained were 7.29 and 4.88, respectively, with an ICER of €9,515 per life-year gained, an ICUR of €11,345 per QALY gained, and an INMB of €12,104. In scenario analyses, considering maximum selling prices for all other drugs, ICUR decreased to €11,311 per QALY and €7,498 per QALY when a 10% and 20% discount, respectively, was applied to the olaparib official price, and the INMB increased to €12,186 and €21,366, respectively. DSA found that the model results were most sensitive to the proportion of patients with relapsing disease in response to platinum-based chemotherapy, time receiving olaparib first-line maintenance treatment, and subsequent treatments price. According to PSAresults, olaparib was associated with a probability of being cost-effective at a €16,372 per QALY WTP threshold ranging from 70% to 100% in the scenarios examined. IMPLICATIONS: Our analysis indicates that olaparib maintenance therapy may deliver a significant health benefit with a contained upfront cost during a 50-year time horizon, from the Italian NHS perspective, providing value in a setting with curative intent.