Prediction of disease-free survival for precision medicine using cooperative learning on multi-omic data.

In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. Our aim is to leverage the advantages of cooperative learning for the computation of polygenic hazard score models via Cox's proportional hazard model, thereby improving the prediction of the disease-free survival. In our experimental study, we apply our methodology to forecast the disease-free survival for Alzheimer's disease (AD) using three layers of data. One layer contains epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status and 10 leading principal components. Another layer contains selected genomic loci, and the last layer contains methylation data for selected CpG sites. We demonstrate that the survival curves computed via cooperative learning yield an AUC of around $0.7$, above the state-of-the-art performance of its competitors. Importantly, the proposed methodology returns (1) a linear score that can be easily interpreted (in contrast to machine learning approaches), and (2) a weighting of the predictive power of the involved data layers, allowing for an assessment of the importance of each omic (or other) platform. Similarly to polygenic hazard score models, our methodology also allows one to compute individual survival curves for each patient.

Locally advanced nasopharyngeal carcinoma in adolescents treated with tomotherapy: Experience at King Faisal Specialist Hospital and Research Centre.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare disease worldwide; To the best of our knowledge, there is no established standard of care specifically tailored for the adolescent population. The majority of existing research relies on retrospective data analysis. OBJECTIVE: Evaluate clinical features, treatment results, prognostic factors and late toxicities of locally advanced NPC patients treated with tomotherapy. DESIGN: Retrospective. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: Between January 2007 and January 2020, we treated patients with NPC, aged between 14 and 21 years, with concomitant chemoradiotherapy using tomotherapy at our institution. We prospectively collected details of clinical characteristics, treatment modalities, outcomes and prognostic factors of these patients and then analysed them retrospectively. MAIN OUTCOME MEASURES: 3-5 years overall survival (OS), 3-5 years locoregional control rate, 3-5 years disease-free survival (DFS), prognostic factors. SAMPLE SIZE: 51 patients. RESULTS: There were 26 male and 25 female patients included in our study. The mean age was 16.5 years, 5 (9.8%) patients with stage III, and 46 (90.2%) with stage IVa according to the American Joint Committee on Cancer, 8th edition staging system. Most patients (98%) received two or more cycles of induction chemotherapy. All patients received concomitant chemoradiotherapy. The median total dose of radiotherapy delivered was 6600 cGy (range 4800-7000). With a median follow-up of 73 months (range 9-168 months), a 5-year locoregional control rate, 5-year OS and 5-year DFS rates were 100%, 86.8% and 71.7%, respectively. Five years later, disease control was 71.7%. Ten (19.6%) patients had disease recurrence in the form of distant metastases during the follow up. CONCLUSIONS: Helical tomotherapy has an excellent late toxicity profile without compromising clinical outcome for patients with NPC. Radiotherapy remains the mainstay of treatment of nasopharyngeal carcinoma to achieve remarkable local control rates. LIMITATIONS: Single institution experience, small number of patients, and retrospective design.

Prognostic importance of modified geriatric nutritional risk index in oral cavity squamous cell carcinoma.

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan-Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.

The ratio of intratumoral CD15+ neutrophils to CD8+ lymphocytes predicts recurrence in patients with gastric cancer after curative resection.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is an independent prognostic indicator of various cancers. AIMS: In this study, we aimed to investigate the prognostic relevance of the intratumoral immune cell balance in gastric cancer. METHODS AND RESULTS: The study included 82 patients who underwent curative resection for gastric cancer. The intratumoral cluster of differentiation (CD) 15- and CD8-positive cells were evaluated using immunohistochemical staining. Additionally, clinicopathological factors and prognoses were analyzed. Patients with high intratumoral CD15/CD8 ratios had significantly lower overall survival (OS) and relapse-free survival (RFS) compared to those with low CD15/CD8 ratios (p = .0026 and p < .0001, respectively). Additionally, a high CD15/CD8 ratio was associated with lymph node metastasis (p = .019). Patients with high NLR had a significantly lower RFS than those with low NLR (p = .0050). Multivariate analysis revealed that the intratumoral CD15/CD8 ratio, NLR, and venous invasion were independent prognostic indicators of RFS (CD15/CD8 ratio: p < .001, hazard ratio (HR) = 14.7, 95% confidence interval (CI) = 3.8-56.8; NLR: p = .010, HR = 5.4, 95% CI = 1.5-19.6; venous invasion: p = .005, HR = 7.4, 95% CI = 1.8-29.7). CONCLUSION: In summary, we found that the intratumoral CD15/CD8 ratio is an independent prognostic factor following gastric cancer resection and its increase is associated with lymph node metastasis and microscopic lymph vessel invasion. Immunological evaluation with additional aspects of innate immunity may be useful in predicting cancer prognosis.

Immunohistochemical co-expression of PAX2 and CAIX predicts better prognosis in clear cell renal cell carcinoma after nephrectomy: A retrospective observational study.

Clear cell renal cell carcinoma (ccRCC) is a lethal malignancy with high metastatic probability. Paired box 2 gene product (PAX2) carbonic anhydrase IX were biomolecules closely linked with ccRCC development and outcomes of multiple malignancies. We aim to explore the role of immunohistochemical staining of PAX2 and CAIX to predict ccRCC prognosis after nephrectomy. Surgical specimens of patients who were pathologically diagnosed as ccRCC were reviewed. Expression levels of PAX2 and CAIX were assessed via immunohistochemical staining. Recurrence-free survival (RFS) and overall survival were compared among different phenotypes. Inverse probability of treatment weighting (IPTW) was used for adjustment of confounding factors. 56 patients were included. Patients with PAX2 and CAIX high-expression (the two-high group, n=8) had significantly longer RFS and OS than those of simultaneously down-expression (the two-low group, n=31). Median RFS was 38.4 (95% CI: 32.3-NA) for the two-high group and 14.8 (95% CI: 13.4-39.0) months for the two-low group (P=0.043). IPTW confirmed PAX2 and CAIX co-expression is associated with less recurrence risk HR: 0.39, 95% CI: 0.17-0.92, P=0.031). Co-expression of PAX2 and CAIX is associated better prognosis of ccRCC. We are looking for validation by large cohort studies.

Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited. METHODS: We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses. RESULTS: Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease. CONCLUSIONS: In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).

Circulating tumor cells are a good predictor of tumor recurrence in clinical patients with gastric cancer.

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101-0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169-8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071-0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28-80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.

Novel prognostic nomograms for postoperative patients with oral cavity squamous cell carcinoma in the central region of China.

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

Impact of red blood cell distribution width (RDW) on postoperative outcomes in hepatocellular carcinoma (HCC) patients.

This study examines the relationship between red blood cell distribution width (RDW) and the prognosis of patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Additionally, it explores the potential effect of RDW for the early identification of high-risk patients after surgery, advocating for timely interventions to improve outcomes. A comprehensive literature search was conducted on May 16, 2022, across PubMed (23 studies), Embase (45 studies), the Cochrane Library (1 study), and CNKI (17 studies), resulting in 6 relevant articles after screening. This analysis primarily focused on the postoperative outcomes of patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to assess prognosis, with survival indicators including overall survival (OS) and disease-free survival (DFS). All 6 studies reported on OS, and 2 addressed DFS. A total of 1645 patients from 6 studies were included. The pooled analysis revealed that RDW is an independent prognostic factor for both OS (HR = 1.50, I²â€…= 84%, 95% CI = 1.23-1.77, P < .01) and DFS (HR = 2.06, I²â€…= 15%, 95% CI = 1.51-2.82, P < .01). Patients in the high RDW group exhibited significantly poorer OS and DFS compared to those in the low RDW group. RDW is a prognostic factor for HCC patients after surgery. Elevated RDW levels are associated with a poorer prognosis, adversely affecting both OS and DFS. RDW may serve as a valuable marker for stratifying risk and guiding intervention strategies in the postoperative management of HCC patients.

Neoadjuvant chemotherapy-induced hemoglobin decline as a prognostic factor in osteosarcoma around the knee joint: a single-center retrospective analysis of 242 patients.

PURPOSE: Anemia is relatively common in cancer patients, and is associated with poor survival in patients with various malignancies. However, how anemia would affect prognosis and response to neoadjuvant chemotherapy (NAC) in osteosarcoma (OS) is still without substantial evidence. METHODS: We retrospectively analysed 242 patients with stage II OS around the knee joint in our institute. Changed hemoglobin (Hb) levels (before and after NAC) were recorded to assess the prognostic value in DFS (disease-free survival) and tumor response to NAC. Univariate and multivariate analyses were conducted to identify prognostic factors related with outcome in OS patients. RESULTS: The mean Hb level significantly decreased after NAC (134.5 ± 15.3 g/L vs. 117.4 ± 16.3 g/L). The percentage of mild (21%), moderate (4.2%) and severe (0%) anemia patients markedly increased after NAC: 41%, 24% and 4.1% respectively. There was higher percentage of ≥ 5% Hb decline in patients with tumor necrosis rate < 90% (141 out of 161), compared with those with tumor necrosis rate ≥ 90% (59 out of 81). Further univariate and survival analysis demonstrated that Hb decline had a significant role in prediction survival in OS patients. Patients with ≥ 5% Hb decline after NAC had an inferior DFS compared with those with < 5% Hb decline. CONCLUSION: In osteosarcoma, patients with greater Hb decrease during neoadjuvant treatment were shown to have worse DFS and a poorer response to NAC than those without. Attempts to correct anemia and their effects on outcomes for osteosarcoma patients should be explored in future studies.

Clinical association between plan complexity and the local-recurrence-free-survival of non-small-cell lung cancer patients receiving stereotactic body radiation therapy.

PURPOSE: To investigate the clinical impact of plan complexity on the local recurrence-free survival (LRFS) of non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). METHODS: Data from 123 treatment plans for 113 NSCLC patients were analyzed. Plan-averaged beam modulation (PM), plan beam irregularity (PI), monitor unit/Gy (MU/Gy) and spherical disproportion (SD) were calculated. The γ passing rates (GPR) were measured using ArcCHECK 3D phantom with 2 %/2mm criteria. High complexity (HC) and low complexity (LC) groups were statistically stratified based on the aforementioned metrics, using cutoffs determined by their significance in correlation with survival time, as calculated using the R-3.6.1 packages. Kaplan-Meier analysis, Cox regression, and Random Survival Forest (RSF) models were employed for the analysis of local recurrence-free survival (LRFS). Propensity-score-matched pairs were generated to minimize bias in the analysis. RESULTS: The median follow-up time for all patients was 25.5 months (interquartile range 13.4-41.2). The prognostic capacity of PM was suggested using RSF, based on Variable Importance and Minimal Depth methods. The 1-, 2-, and 3-year LRFS rates in the HC group were significantly lower than those in the LC group (p = 0.023), when plan complexity was defined by PM. However, no significant difference was observed between the HC and LC groups when defined by other metrics (p > 0.05). All γ passing rates exceeded 90.5 %. CONCLUSIONS: This study revealed a significant association between higher PM and worse LRFS in NSCLC patients treated with SBRT. This finding offers additional clinical evidence supporting the potential optimization of pre-treatment quality assurance protocols.

Prognostic and clinicopathological value of Ki-67 in patients with oesophageal squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC. DESIGN: The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES: Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023. STATISTICAL METHODS: Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I2 statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I2>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs. RESULTS: 11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location. CONCLUSIONS: In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.

[Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma: analysis of 653 cases].

OBJECTIVE: To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma. METHODS: We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, n=111), chemotherapy (CT group, n=108) and clinical observation (CO group, n=434). RESULTS: In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group (P < 0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group (P < 0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age (P < 0.05; HR=0.631, 95% CI: 0.401-0.993), solid nodules (P < 0.01; HR=7.620, 95% CI: 3.037-19.121), micropapillary or solid component (P < 0.05; HR= 1.776, 95% CI: 1.010-3.122), lymphovascular invasion (P < 0.05; HR=2.981, 95% CI: 1.198-7.419), and adjuvant therapy (P < 0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% vs 9.0%). CONCLUSION: Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Clinicopathological characteristics and prognostic significance of casting-type calcifications in patients with invasive breast cancer presenting with microcalcification.

To explore the clinicopathological characteristics and prognostic significance of casting-type calcification (CC) in patients with breast cancer presenting with microcalcification on mammography. Data on patients with invasive breast cancer who had mammographic calcification was retrospectively analyzed. The chi-square test was utilized to assess the clinicopathological characteristics of two forms of CC-related breast cancer. The examination of prognostic variables was conducted using Kaplan-Meier and Cox regression analyses. A total of 427 eligible patients were included in this study. Chi-square analysis indicated that the presence of CC was associated with estrogen receptor (ER) negativity (P = 0.005), progesterone receptor (PR) negativity (P < 0.001), and epidermal growth factor receptor 2 (HER-2) positivity (P < 0.001); among these, the association was stronger with the CC-predominant type. After a median follow-up of 82 months, those with CC had a worse 5-year recurrence-free survival (RFS) (77.1% vs. 86.9%, p = 0.036; hazard ratio [HR], 1.86; 95% confidence interval [CI] 1.04-3.31) and overall survival (OS) (84.0% vs. 94.4%, p = 0.007; HR, 2.99; 95% CI 1.34-6.65) rates. In COX regression analysis, such differences were still observed in HER-2 positive subgroups (RFS: HR: 2.45, 95% CI 1-5.97, P = 0.049; OS: HR: 4.53, 95% CI 1.17-17.52, P = 0.029). In patients with invasive breast cancer exhibiting calcifications on mammography, the presence of CC, especially the CC-predominant type, is linked to a higher frequency of hormone receptor negativity and HER-2 positivity. The presence of CC is associated with an unfavorable 5-year RFS and OS rates.

Association Between Preoperative Osteopenia and Prognosis in Breast Cancer Patients.

BACKGROUND/AIM: Osteopenia, the loss of bone mineral density (BMD), was recently reported as a prognostic factor in various cancers. However, the prognostic significance of preoperative osteopenia in breast cancer remains unclear. This study aimed to clarify the clinical significance of preoperative osteopenia in breast cancer. PATIENTS AND METHODS: We retrospectively analyzed the relationship between osteopenia and clinical factors and prognosis in 532 patients with pathological Stage I-III primary breast cancer between 2009 and 2017. Osteopenia was assessed by measuring the average pixel density (Hounsfield unit) in the midvertebral core of the 11th thoracic vertebra on enhanced preoperative computed tomography. RESULTS: Osteopenia was diagnosed in 186 (35.0%) patients. The recurrence-free survival (RFS) rate was significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0275), but there was no significant difference in overall survival (OS) between the two groups. When evaluated by menopausal status, RFS and OS were significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0094 and p=0.0264, respectively) in premenopausal patients. However, there were no significant differences in RFS and OS between the two groups among postmenopausal patients. In premenopausal patients, osteopenia was an independent prognostic factor for RFS in a multivariate analysis (p=0.0266). CONCLUSION: Preoperative osteopenia was independently associated with recurrence of breast cancer.

The 8th AJCC classification is inferior to a new neck stage based on intraparotid lymph node in parotid gland cancer.

BACKGROUND: Lymph node (LN) status is an important prognostic factor for parotid gland cancer (PGC). This study aimed to analyze the impact of extranodal extension (ENE) of intraparotid LN and LN metastasis burden on survival in PGC. METHODS: Patients with surgically treated PGC and at least one metastatic cervical LN were retrospectively enrolled. Primary outcome variables were distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). The impact of ENE and LN metastasis burden was assessed using the Cox model. RESULTS: A total of 292 patients were included. ENE in cervical or intraparotid LN was not associated with DMFS, DSS, or OS. Intraparotid LN metastasis had a significant impact on prognosis, and the presence of only one metastatic intraparotid LN offered an approximately 1.5-fold risk of distant metastasis. Prognostic models based on the number of positive LNs (1 vs. 2-3 vs. 4+) were superior to the AJCC N stage in terms of DMFS, DSS, and OS. CONCLUSIONS: ENE of cervical or intraparotid LN has a limited effect on the prognosis of PGC, and the number of positive LNs is better than the AJCC N stage in LN status evaluation.

Robotic versus laparoscopic distal gastrectomy for resectable gastric cancer: a randomized phase 2 trial.

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate.

Hyperthermic intraperitoneal chemotherapy in colorectal cancer.

BACKGROUND: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. PATIENTS AND METHODS: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. RESULTS: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. CONCLUSIONS: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

Impact of Neoadjuvant Chemotherapy (NAC) on Biomarker Expression in Breast Cancer.

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02-0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86-182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.

Clinicopathologic Analysis and Prognostic Factors for Survival in Patients with Operable Ampullary Carcinoma: A Multi-Institutional Retrospective Experience.

Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.