Postoperative Chemotherapy Regimen Research Articles

Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus.

Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus (RGAVCT) have a poor prognosis, with a 5-year survival rate ranging from 18.42%-53.57%. These patients need a reasonable postoperative treatment plan to improve their prognosis. To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT. We retrospectively collected the clinicopathological data of 530 patients who underwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus. Furthermore, we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by assessing the clinical and pathological features of the patients who met the inclusion criteria. We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses. The subgroups of patients with stages I, II, and III disease who received single-, dual-, or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0. In all, 530 eligible individuals with RGAVCT were enrolled in this study. The median overall survival (OS) of patients with RGAVCT was 24 months, and the survival rates were 80.2%, 62.5%, and 42.3% at 12, 24, and 59 months, respectively. Preoperative complications, tumor size, T stage, and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model. A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage I or II RGAVCT; however, chemotherapy did have an effect on OS of stage III patients. Stage III patients who were treated with chemotherapy consisting of dual- or triple-agent regimens had better survival than those treated with single-agent regimens, and no significant difference was observed in the survival of patients treated with chemotherapy consisting of dual- or triple-agent regimens. For patients with stage III RGAVCT, a dual-agent regimen of postoperative chemotherapy should be recommended rather than a triple-agent treatment, as the latter is associated with increased frequency of adverse events.

Analysis of sequential chemotherapy efficacy in ovarian epithelial carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel's Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

Screening optimal candidates with operable, early-stage triple-negative breast cancer benefitting from capecitabine maintenance: A post-hoc analysis of the SYSUCC-001 study

BackgroundTo explore whether specific clinicopathological covariates are predictive for a benefit from capecitabine maintenance in early-stage triple-negative breast cancer (TNBC) in the SYSUCC-001 phase III clinical trial. MethodsCandidate covariates included age, menstrual status, type of surgery, postoperative chemotherapy regimen, Ki-67 percentage, histologic grade, primary tumor size, lymphovascular invasion, node status, and capecitabine medication. Their nonlinear effects were modeled by restricted cubic spline. The primary endpoint was disease-free survival (DFS). A survival prediction model was constructed using Cox proportional hazards regression analysis. ResultsAll 434 participants (306 in development cohort and 128 in validation cohort) were analyzed. The estimated 5-year DFS in development and validation cohorts were 77.8 % (95 % CI, 72.9%–82.7 %) and 78.2 % (95 % CI, 70.9%–85.5 %), respectively. Age and node status had significant nonlinear effects on DFS. The prediction model constructed using four covariates (node status, lymphovascular invasion, capecitabine maintenance, and age) demonstrated satisfactory calibration and fair discrimination ability, with C-index of 0.722 (95 % CI, 0.662–0.781) and 0.764 (95 % CI, 0.668–0.859) in development and validation cohorts, respectively. Moreover, patient classification was conducted according to their risk scores calculated using our model, in which, notable survival benefits were reported in low-risk subpopulations. An easy-to-use online calculator for predicting benefit of capecitabine maintenance was also designed. ConclusionsThe evidence-based prediction model can be readily assessed at baseline, which might help decision making in clinical practice and optimize patient stratification, especially for those with low-risk, capecitabine maintenance might be a potential strategy in the early-disease setting.

Bedaquiline in the postoperative period of complex therapy of tuberculosis

Introduction. The experience of domestic phthisiatry, which has been using bedaquiline for more than 10 years, testifies to the efficacy and safety of the drug for the treatment of drug-resistant forms of tuberculosis. At the present stage, the evaluation of the effect and safety of bedaquiline in the postoperative stage of chemotherapy, including patients with HIV/tuberculosis co-infection, becomes the most relevant.Aim. To evaluate the results of bedaquiline application in the postoperative stage of complex tuberculosis therapy.Materials and methods. Results of a retrospective study of medical records of 57 patients. The inclusion criterion was the surgery performed for tuberculosis and the presence of bedaquiline in the postoperative chemotherapy regimen. Frequency of tuberculosis progression 1 month after surgery was evaluated as an efficacy criterion. The frequency of QTc interval prolongation with clinical manifestations, frequency and nature of hepatotoxic reactions were evaluated as the drug safety criterion.Results. In the absolute majority of patients – 54 (94.7%) postoperative period, during which bedaquiline was used, proceeded without complications. Cases of tuberculosis progression were observed only in patients with severe concomitant diseases. Undesirable side effects on bedaquiline were observed in 9 (15.8%) patients, the absolute majority of patients resumed taking the drug in full after drug correction. The average duration of bedaquiline prescription was 282 ± 5 doses.Conclusions. The use of bedaquiline in the postoperative period increases the effectiveness of complex therapy and prevents progression of tuberculosis and according to our data should be regarded as safe. Administration of bedaquiline in patients with HIV/tuberculosis co-infection also contributes to the positive result of the therapy. Repeated courses of bedaquiline after surgical intervention, including in patients with HIV/tuberculosis co-infection, prevent progression of tuberculosis in the postoperative period. The tolerability of the bedaquiline-containing regimen in this category of patients, including long courses of more than 24 weeks, was assessed as quite satisfactory.

Advances in three-dimensional tumor models for colorectal cancer

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.

A correlation study affecting survival in patients after radical colon cancer surgery: A retrospective study.

The objective of this study was to explore the relevant factors affecting the 5-year survival rate of patients after radical colon cancer surgery, and to provide some basis for improving the quality of life and prognosis of colon cancer patients. The clinical data of 116 colon cancer patients who underwent treatment in our hospital from January 2017 to December 2017 were retrospectively selected. Using the date of performing surgical treatment as the starting point and the completion of 5 years after surgery or patient death as the end point, all patients were followed up by telephone to count the 5-year survival rate and analyze the influence of each factor with the prognosis of colon cancer patients. Of the 116 patients, 14 patients were lost to follow-up. Of the 102 patients with complete follow-up, 33 patients were died, with an overall 5-year survival rate of 67.6%. After univariate analysis, it was found that distant metastasis (χ2 = 10.493, P = .001), lymph node metastasis (χ2 = 25.145, P < .001), depth of muscle infiltration (χ2 = 14.929, P < .001), alcohol consumption (χ2 = 15.263, P < .001), and preoperative obstruction (χ2 = 9.555, P = .002) were significantly associated with the prognosis of colon cancer patients. Multivariate logistic analysis showed that distant metastasis (odds ratio [OR]: 1.932, 95% confidence intervals [CI]: 1.272-2.934, P = .002), lymph node metastasis (OR: 1.219, 95% CI: 1.091-1.362, P < .001), and obstruction (OR: 1.970, 95% CI: 1.300-2.990, P < .001) were significant independent risk factors affecting the prognosis in patients after radical colon cancer surgery. In summary, preoperative obstruction, lymph node metastasis, and distant metastasis are independent factors influencing 5-year survival rate after radical colon cancer surgery. Patients with risk factors should be followed up more closely and reasonable postoperative adjuvant chemotherapy regimens should be used to improve long-term survival.

Elderly Pancreatic Adenocarcinoma Cancer Patients Could Benefit From Postoperative Chemotherapy.

The study aim to investigate whether elderly patients with resectable pancreatic ductal adenocarcinoma (PDAC) could benefit from postoperative chemotherapy. This study selects the data of PDAC patients who were diagnosed between 2004 and 2014 from the Surveillance, Epidemiology, and End Results program. Median overall survival (mOS) is determined by Kaplan-Meier survival curves. Multivariate logistic regression analysis and hazard ratio are employed to assess the association among potential prognostic factors. Propensity score matching evaluation is used to reduce bias. In total, there are 11,865 PDAC patients selected from the Surveillance, Epidemiology, and End Results database. Elderly PDAC patients have poor prognoses compared with younger (mOS, 15 vs 21 months). The possible reason might be that the elderly patients are less likely to receive postoperative chemotherapy. After propensity score matching, it is found that, for those who receive postoperative chemotherapy, although the mOS of older group is not as good as that of the younger group (mOS, 20 vs 23 months; 18-month survival rate: 53.4% vs 61.3%), the mOS of older group prolonged by postoperative chemotherapy is similar to that of younger group (9 vs 9 months). Elderly PDAC patients (≥70 years) might benefit from the currently used postoperative chemotherapy regimens.

The Number of Positive Tumor Markers (NPTM) Achieves Higher Value in the Prognosis Prediction of Gastric Cancer.

The clinical application of combined tumor markers is still limited. We aim to explore the value of the combination of multiple tumor markers in gastric cancer (GC) prognosis. The prognostic significance was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The estimated area under the curve (AUC) was compared to evaluate the discriminatory ability of different indicators. A nomogram was constructed based on the results of multivariable cox regression, and its performance was evaluated by Harrell's concordance index and calibration curve. NPTM (number of positive tumor markers) displayed independent prognostic significance whether in the whole cohort or in patients with different stages. Patients with the all-negative tumor markers had a worse prognosis after postoperative chemotherapy in all cohort (P = 0.023) or in age ≤60 subgroup (P = 0.012), while patients with positive tumor markers had a better prognosis after postoperative chemotherapy in stage III (P = 0.012). The AUC value of NPTM is higher than any individual tumor marker. The 1-, 3-, and 5-year AUC values of the CTNM (combination of NPTM and pTNM) increased by 5%, 4.8%, and 3.6%, respectively, compared with TNM staging system. The nomogram constructed including NPTM showed its high accuracy (C - index = 0.706) versus TNM staging system (C - index = 0.646) and CTNM (C - index = 0.681). NPTM was an independent predictor of gastric cancer prognosis, showing more accurate prognostic performance than individual tumor markers. Especially its significance in guiding postoperative adjuvant chemotherapy regimens and predicting prognosis by combination with TNM staging system may have a better clinical application value.

Investigation of the optimal platinum-based regimen in the postoperative adjuvant chemotherapy setting for early-stage resected non-small lung cancer: a Bayesian network meta-analysis

ObjectiveThis study aimed to compare the efficacy and safety of different platinum adjuvant chemotherapy regimens for early-stage resected non-small-cell lung cancer (NSCLC).DesignSystematic review with network meta-analysis of randomised trials.Data sourcesPubMed,...

Data-driven treatment pathways mining for early breast cancer using cSPADE algorithm and system clustering.

Due to the multidimensional, multilayered, and chronological order of the cancer data, it was challenging for us to extract treatment paths. To determine whether the cSPADE algorithm and system clustering proposed in this study can effectively identify the treatment pathways for early breast cancer. We applied data mining technology to the electronic medical records of 6891 early breast cancer patients to mine treatment pathways. We provided a method of extracting data from EMR and performed three-stage mining: determining the treatment stage through the cSPADE algorithm → system clustering for treatment plan extraction → cSPADE mining sequence pattern for treatment. The Kolmogorov-Smirnov test and correlation analysis were used to cross-validate the sequence rules of early breast cancer treatment pathways. We unearthed 55 sequence rules for early breast cancer treatment, 3 preoperative neoadjuvant chemotherapy regimens, three postoperative chemotherapy regimens, and 2 chemotherapy regimens for patients without surgery. Through 5-fold cross-validation, Pearson and Spearman correlation tests were performed. At the significance level of p<0.05, all correlation coefficients of support, confidence and lift were greater than 0.89. Using the Kolmogorov-Smirnov test, we found no significant differences between the sequence distributions. We have proved that cSPADE algorithm combined system clustering is an effective technique for identifying temporal relationships between treatment modalities, enabling hierarchical and vertical mining of breast cancer treatment models. In addition, we confirmed the robustness of the results by cross-validation of these treatment pathway ordering rules. Through this method, the treatment path of early breast cancer patients can be revealed, and the real-world breast cancer treatment behaviour model can be evaluated, which can provide reference for the redesign and optimization of treatment path.

High SMAD4 Expression is Associated With Better Clinical Outcomes in Patients With Resectable Pancreatic Cancer: An Analysis of NRG Oncology/RTOG 9704

SMAD4 (DPC4) is a transcription factor that mediates TGF-beta signal transduction and is mutationally in-activated in about one-third of pancreatic cancer (PC). Studies have suggested that SMAD4 loss is associated with a higher rate of distant metastasis (DM), but other studies have refuted this claim. An assessment of SMAD4 expression was performed in NRG/RTOG 9704, a prospective phase III trial comparing different post-operative chemotherapy regimens combined with 5-fluorouracil-based chemoradiation for resectable PC. It was hypothesized that higher SMAD4 expression is associated with lower incidence of DM and better disease-free and overall survival (DFS & OS).An automated quantitative immunofluorescence SMAD4 analysis was performed in pan-cytokeratin positive tumor cells on a tissue microarray with samples from NRG/RTOG 9704, using a microscope and image analysis software. Total cellular SMAD4 was analyzed as a categorical variable dichotomized by the median. DFS & OS were estimated with the Kaplan-Meier method & groupings compared with the log-rank test. Local-regional recurrence (LRR) & DM were estimated by the cumulative incidence method & groupings compared with Gray's test. Univariate & multivariable Cox proportional hazards (OS & DFS) or Fine-Gray (DM & LRR) regression models were used to evaluate associations between SMAD4 & outcomes. SMAD4 was included in all models; stepwise selection identified significant variables among treatment, age, gender, race, CA19-9, tumor location & diameter, nodes, & surgical margin status.Of 451 eligible patients on NRG/RTOG 9704, tissue from 141 patients was analyzable. There were no significant differences in baseline characteristics/outcomes for patients with & without tissue. There were no statistically significant differences in baseline characteristics between the low & high SMAD4 groupings. High SMAD4 expression was associated with better DFS & OS compared to low SMAD4, with a 32% risk reduction (RRed) of DFS failure [HR (95% CI): 0.68 (0.48, 0.97); P = 0.03] & a 31% RRed of death [HR (95% CI): 0.69 (0.48, 0.99); P = 0.04]. This difference in DFS appeared to be due to a lower incidence of DM in tumors with high SMAD4, with a 31% RRed of failing distantly [HR (95% CI): 0.69 (0.48, 0.99), P = 0.048]. No differences were detected in LRR. After adjusting for CA19-9 on multivariable analysis, high SMAD4 remained associated with better DFS with a 34% RRed of failing [HR (95% CI): 0.66 (0.46, 0.96), P = 0.03]. Tumors with high SMAD4 showed a trend of being associated with less DM [HR (95% CI): 0.68 (0.46, 1.004), P = 0.052], after adjusting for age & surgical margin status.Tumor expression of SMAD4 is significantly associated with better clinical outcome, specifically lower DM and higher DFS and OS, in tumor samples from a large, phase III randomized trial of resectable pancreatic cancer.

Postoperative adjuvant chemotherapy for resectable cholangiocarcinoma.

Postoperative adjuvant chemotherapy for resectable cholangiocarcinoma.

An intrathecal limited postoperative chemotherapy regimen for the treatment of young children with nodular/desmoplastic medulloblastoma and medulloblastoma with extensive nodularity

Therapy for medulloblastoma in patients < 4years old omits radiotherapy due to anticipated neurocognitive deficits. The German Pediatric Brain Tumor Study Group described a chemotherapy regimen (HIT-SKK' 92 and HIT-SKK 2000) without radiation which yielded a 5-year progression-free survival (PFS) rate of 85% in children with nodular/desmoplastic medulloblastoma (NDMB) and medulloblastoma with extensive nodularity (MBEN). We modified the HIT-SKK regimen to reduce the total number of intrathecal methotrexate (IT MTX) doses from 12 to 2 doses/cycle and obviate Ommaya reservoir implantation through the use of lumbar administration. We report the outcomes of five patients treated with our approach. IT MTX was eliminated altogether on weeks when high-dose intravenous methotrexate was administered. On weeks when no systemic methotrexate was administered, a single dose of lumbar-administered IT MTX was substituted in place of multiple intra-Ommaya doses. Cumulative dosing of MTX was 16-24mg/cycle (age-based) compared to 24mg/cycle in the HIT-SKK regimen. Following chemotherapy, patients were monitored with interval imaging, observation for acute and late effects, and survival. Four children remained in remission 3, 5, 9, and 10years post-treatment respectively, without observed learning difficulties. One child had recurrent tumor and metastasis 6months post-treatment. She failed the attempted salvage regimen and continued to deteriorate, dying of disease at 3years old. Review of existing literature supported our modifications well. While this report is limited by the small number of children treated, we believe there is encouraging evidence that our approach warrants further evaluation in a larger population of young children with NDMB and MBEN.

P01.18 Adjuvant Chemotherapy With Modified Nab-Paclitaxel and Carboplatin for Completely Resected NSCLC: Survival Analysis of FAST-Nab.

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA non-small cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m2) on days 1 and 8 followed by carboplatin area (area under the curve=6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB–IIIA were 85.4% and 63.9%, respectively (P=0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P=0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II–IIIA were 83.6% and 63.6%, respectively (P=0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P=0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

Prognostic factors for cytology-positive gastric cancer: a multicenter retrospective analysis.

The prognosis of patients with gastric cancer and positive peritoneal lavage cytology is poor, even after gastrectomy. Though the standard therapy for this population is radical gastrectomy followed by S-1 chemotherapy, treatments vary among institutions and eras. We conducted a multicenter retrospective study to investigate the prognostic factors for cytology-positive gastric cancer. We reviewed the medical records obtained from 6 institutions, covering 2000-2019. There were 128 patients with positive cytology and no other distant metastases that underwent R1 gastrectomy. Univariate and multivariate analyses to identify prognostic factors for overall survival were conducted using Cox's proportional hazards models. The median overall survival time was 18.6months. In univariate analyses, age (≥ 80years vs. < 70years), performance status (2, 3 vs. 0), prognostic nutritional index (< 35 vs. ≥ 40), the extent of lymphadenectomy (D1 vs. ≥ D2), macroscopic type (type 4 vs. non-type 4), and postoperative chemotherapy (none vs. S-1) were significantly correlated with worse survival. Multivariate analysis revealed that lymph node metastasis (pN3b vs. pN0, hazard ratio 4.46, 95% confidence interval 1.17-16.9, p = 0.03) and postoperative chemotherapy (none vs. S-1, hazard ratio 2.28, 95% confidence interval 1.16-4.45, p = 0.02) were independent risk factors for death. No postoperative chemotherapy regimen showed a survival benefit over S-1 monotherapy. Massive lymph node metastasis was an independent risk factor in cytology-positive gastric cancer. Postoperative chemotherapy was also an independent prognostic factor, though the most beneficial regimen was still uncertain.

Efficacy of Postoperative FOLFOX Versus XELOX Chemotherapy for Gastric Cancer and Prognostic Value of Platelet-Lymphocyte Ratio in Patients Receiving XELOX.

BackgroundSurgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet–lymphocyte ratio (PLR) in the XELOX group.MethodsPatients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan–Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.ResultsPatients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX (P < 0.001), especially for stage III GC (P = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.ConclusionXELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.

Outcome of first relapse of Hodgkin lymphoma: single institution experience.

To determine outcome of first relapse of Hodgkin lymphoma with standard dose chemotherapy, and to identify the prognostic factors predicting survival outcome in paediatric patients. The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of Hodgkin lymphoma patients who relapsed at least 3 months after the completion of initial treatment from January 2001 to December 2010. Probabilities of overall survival, event-free survival and cumulative incidence were calculated. Data was analysed using SPSS 21. Of the 43 patients, 31(72%) were males and 12(29%) were females. Mean age at relapse was 11±3.3 years (range: 4-17 years). In 31(72%) patients, early post-operative intraperitoneal chemotherapy was employed. Median follow-up of the cohort was 62 months (interquartile range: 4-187 months). Overall survival and event-free survival at 10 years was 23(54%) and 15(35%) respectively. On univariate analysis, initial disease stage (p=0.021), stage at relapse (p=0.003), treatment protocol (p=0.005), treatment responsiveness at initial two cycles of salvage chemotherapy (p=0.002) and at the end of treatment assessment (p=0.0009) were statistically significant factors. Multivariate cox regression analysis revealed disease stage at relapse (p=0.004), chemotherapy regimen (p=0.025) and end-of-treatment disease evaluation (p=0.005) as the significant variables. Improved outcome with early post-operative intraperitoneal chemotherapy regimen was noted for Hodgkin lymphoma patients who had disease-free interval >2 years.

Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment.

Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.

Feasibility of multi-parametric magnetic resonance imaging combined with machine learning in the assessment of necrosis of osteosarcoma after neoadjuvant chemotherapy: a preliminary study

BackgroundResponse evaluation of neoadjuvant chemotherapy (NACT) in patients with osteosarcoma is significant for the termination of ineffective treatment, the development of postoperative chemotherapy regimens, and the prediction of prognosis. However, histological response and tumour necrosis rate can currently be evaluated only in resected specimens after NACT. A preoperatively accurate, noninvasive, and reproducible method of response assessment to NACT is required. In this study, the value of multi-parametric magnetic resonance imaging (MRI) combined with machine learning for assessment of tumour necrosis after NACT for osteosarcoma was investigated.MethodsTwelve patients with primary osteosarcoma of limbs underwent NACT and received MRI examination before surgery. Postoperative tumour specimens were made corresponding to the transverse image of MRI. One hundred and two tissue samples were obtained and pathologically divided into tumour survival areas (non-cartilaginous and cartilaginous tumour viable areas) and tumour-nonviable areas (non-cartilaginous tumour necrosis areas, post-necrotic tumour collagen areas, and tumour necrotic cystic/haemorrhagic and secondary aneurismal bone cyst areas). The MRI parameters, including standardised apparent diffusion coefficient (ADC) values, signal intensity values of T2-weighted imaging (T2WI) and subtract-enhanced T1-weighted imaging (ST1WI) were used to train machine learning models based on the random forest algorithm. Three classification tasks of distinguishing tumour survival, non-cartilaginous tumour survival, and cartilaginous tumour survival from tumour nonviable were evaluated by five-fold cross-validation.ResultsFor distinguishing non-cartilaginous tumour survival from tumour nonviable, the classifier constructed with ADC achieved an AUC of 0.93, while the classifier with multi-parametric MRI improved to 0.97 (P = 0.0933). For distinguishing tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.83, while the classifier with multi-parametric MRI improved to 0.90 (P < 0.05). For distinguishing cartilaginous tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.61, while the classifier with multi-parametric MRI parameters improved to 0.81(P < 0.05).ConclusionsThe combination of multi-parametric MRI and machine learning significantly improved the discriminating ability of viable cartilaginous tumour components. Our study suggests that this method may provide an objective and accurate basis for NACT response evaluation in osteosarcoma.

Predictors of treatment outcome of Wilms Tumour in low-income country; single centre experience from Pakistan

Wilms tumor (WT) represents around 85% of pediatric renal tumors. In high-income countries, 5-years survival of WT is above 90% but survival in developing countries is inferior. To identify the predictors of treatment outcome of WT in a developing country. A retrospective study conducted at the pediatric oncology department, Combined Military Hospital Rawalpindi, Pakistan. All newly diagnosed WT cases from 1st January 2012 who completed their treatment before 31st August 2019 were evaluated. Treatment was based on SIOP Wilms Tumour 2001/UK version 5. Patients presenting before nephrectomy received pre-operative chemotherapy. The postoperative chemotherapy regimen was decided according to the stage, risk stratification and metastatic status of the patient. Data of 84 cases, including 40 (47.6%) males and 44 (52.4%) females was analyzed. The mean diagnostic age was 38.87±28.66 months and 68 (81%) cases were less than five years of age. The commonest presenting features were abdominal mass in 75 (89.3%) cases. The right kidney was affected in 43 (51.2%) cases. Stage I disease was documented in 27 (32.1%) cases, stage II in 25 (29.8%), stage III in 13 (15.5%), and stage IV in 17 (20.2%) cases. In univariate analysis, advanced stage (P = < 0.001) and metastatic disease (P=< 0.001) adversely affected the treatment outcome. Multivariate analysis demonstrated that advanced stage WT was associated with the worst outcome (P= < 0.05). Four (4.8%) cases had treatment-related mortality (TRM). With a median follow-up time of 28.26±23.03 months, OS and EFS were 66 (78.6%) and 63 (75.0%) respectively. Delayed presentation with advanced-stage metastatic disease is quite common in the developing courtiers and is the major contributor to decreased EFS and OS. In the present study, 20.2% cases had metastatic disease, which is similar to reported from other developing countries. OS decreased from 92.6% in stage I to 47.1% in stage IV disease (P=< 0.001) and EFS decreased from 92.6% in stage I to 43.8% in stage IV disease (P=< 0.001). Very similar results are reported by a regional study [17]. Results in stage I and II disease are comparable to documented in the western world and inferior in advanced-stage disease. The strength of the present study is that multiple factors, affecting the treatment outcome of WT over almost seven years period were evaluated. Stage of the disease is the most important prognostic factor. Delayed presentation with metastatic disease has a poor outcome.