Longer Disease-free Survival Research Articles

Type of recurrence is associated with disease-free survival after salvage surgery for locally recurrent rectal cancer.

To compare the characteristics and outcomes of rectal cancer patients with local recurrence at a perianastomotic site (PA), a surgical field (SF) site, or in lateral lymph nodes (LLN). A total of 114 consecutive patients who underwent surgery for recurrent, non-metastatic rectal cancer at a single comprehensive cancer center between 1997 and 2012 were grouped on the basis of radiographic assessment of type of recurrence: PA, 76 (67%) patients; SF, 25 (22%) patients; LLN, 13 (11%) patients. Demographic, clinical, and pathological features were compared between the three groups, as were disease-free survival (DFS) and overall survival (OS). Recurrence type was associated with positive circumferential margin in the primary resection (PA, 4 [6%]; SF, 4 [19%]; LLN, 3 [25%]; P = 0.027), prior neoadjuvant therapy for the primary tumor (PA, 57 [75%]; SF, 18 [72%]; LLN, 4 [31%]; P = 0.007), and location of the primary tumor in the upper rectum (PA, 33 [45%]; SF, 5 [23%]; LLN, 1 [8%]; P < 0.001). Patients with PA had longer median DFS (PA, 5.1years; SF, 1.5years; LLN, 1.2years; P = 0.036). There was a non-significant trend toward longer OS and higher rates of R0 resection for PA. Type of recurrence after salvage surgery for locally recurrent rectal cancer is associated with longer DFS in patients with PA recurrence.

Reoperation with Total Hysterectomy after Incomplete Surgery Is Helpful in Patients with Incidentally Diagnosed Uterine Leiomyosarcoma

Objective: The aim of this study was to evaluate the impact of initial surgical treatments and surgical re-exploration on the oncological outcomes of patients with incidentally diagnosed uterine leiomyosarcoma (uLMS). Design: A retrospective analysis of 87 patients who underwent re-exploration for incidentally diagnosed uLMS at the Fudan University Shanghai Cancer Center was performed. Methods: Kaplan-Meier and Cox proportional hazards regression models were used for analyses. Results: The median age (range) at diagnosis was 49 (23–76) years. The median disease-free survival (DFS) and overall survival (OS) were 15.1 and 56.7 months, respectively. The Kaplan-Meier curves and log-rank tests showed the median DFS was longer in patients with restaging operation (N = 30) than without (N = 55) (p = 0.017) but no significant difference in median OS (p = 0.142). In patients who underwent myomectomy/subtotal hysterectomy, 5 patients (28.5%) had remnant sarcoma during re-exploration with complete uterine removal, and re-exploration was associated with longer DFS (p = 0.038) and OS (p = 0.042). Limitations: The limitation of this study is its retrospective observational design with a limited number of patients. Conclusion: Reoperation with total hysterectomy after incomplete surgery may be helpful in patients with incidentally diagnosed uLMS at the first treatment.

CD1a- and CD83-positive dendritic cells as prognostic markers of metastasis development in early breast cancer patients.

Dendritic cells (DCs) are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response in different types of cancer. However, the prognostic significance of the accumulation of these cells in human early breast tumors is not totally clear. The aim of this study is to evaluate the prognostic relevance of CD1a( +) and CD83( +) dendritic cells in early breast cancer patients. We conducted immunohistochemical assays to determine the number of stromal CD1a( +) and CD83( +) DCs in primary tumors from early invasive ductal breast cancer patients, and analyzed their association with clinico-pathological characteristics. Patients with high CD1a( +) DC number had lower risk of bone metastatic occurrence, as well as, longer disease-free survival (DFS), bone metastasis-free survival (BMFS) and overall survival (OS). Moreover, CD1a( +) DC number was an independent prognostic factor for BMFS and OS. In contrast, we found that patients with high number of CD83( +) DCs had lower risk of mix (bone and visceral)-metastatic occurrence. Likewise, these patients presented better prognosis with longer DFS, mix-MFS and OS. Furthermore, CD83( +) DC number was an independent prognostic factor for DFS and OS. The quantification of the stromal infiltration of DCs expressing CD1a or CD83 in early invasive breast cancer patients serves to indicate the prognostic risk of developing metastasis in a specific site.

Abstract 624: Clinical evaluation of the MasSpec Pen technology for rapid diagnosis and margin assessment in pancreatic cancer surgery

Abstract Precise removal of pancreatic ductal adenocarcinoma (PDAC) with microscopically negative margins, commonly assessed by frozen section analysis, is associated with longer disease-free survival. However, histologic complexities and tissue-processing artifacts can render frozen section analysis of PDAC margins a challenging and time-consuming task, with reported accuracies dependent on the skillset and subspecialty of the pathologist on call. We developed the MasSpec Pen, a handheld device coupled to a mass spectrometer, for rapid (~15 s) and nondestructive molecular analysis and diagnosis of tissues. The MasSpec Pen supplies a discrete water droplet onto a tissue's surface, allowing diagnostic metabolites and lipids to be extracted into the droplet and then transmitted into a mass spectrometer for analysis. Here, we evaluate the performance of the MasSpec Pen for intraoperative diagnosis of PDAC in human pancreatic and bile duct margins. Pancreatic and bile duct tissue samples (N=157) were obtained from the Cooperative Human Tissue Network and Baylor College of Medicine and stored at -80°C prior to analysis. A Q Exactive mass spectrometer (Thermo Scientific) coupled to the MasSpec Pen was used for analysis of thawed samples in the negative ion mode. Tissues were then cryo-sectioned, H&amp;E stained, and blindly evaluated by a pathologist. Based on the distinct molecular profiles acquired, we generated two statistical classifiers using lasso penalized logistic regression for distinguishing PDAC from healthy pancreas and bile duct tissue based on a sparse set of molecular features indicative of disease state. For distinguishing normal pancreas from PDAC, an overall accuracy of 91.5%, sensitivity of 95.5%, and specificity of 89.7% was achieved for training, validation, and test sets. Classification results for discriminating normal bile duct from PDAC had an overall accuracy of 95%, sensitivity of 92%, and specificity of 100% in training and validation. We have begun clinical testing of the MasSpec Pen in human surgeries following its successful translation to an operating room at Texas Medical Center. To date, the MasSpec Pen has been used to analyze in vivo and fresh ex vivo tissue in 19 pancreatic surgeries. When predicting on 64 intraoperative analyses using classification models built on banked data, 93.8% agreement with final postoperative pathology reports was achieved. While further validation studies are needed, our results show that the MasSpec Pen can distinguish PDAC from normal pancreas and bile duct tissues with high accuracy and is compatible for in vivo use, suggesting this technology may be valuable for near real-time margin evaluation during pancreatic oncologic surgeries. Citation Format: Mary E. King, Jialing Zhang, John Q. Lin, Kyana Y. Garza, Rachel J. DeHoog, Clara L. Feider, Alena V. Bensussan, Marta Sans, Anna Krieger, Sunil Badal, Michael F. Keating, Sadhna Dhingra, Wendong Yu, George Van Buren, Christopher Pirko, Kirtan Brahmbhatt, William E. Fisher, James W. Suliburk, Livia S. Eberlin. Clinical evaluation of the MasSpec Pen technology for rapid diagnosis and margin assessment in pancreatic cancer surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 624.

Oncologic outcome and the optimal time of sequential extended cholecystectomy in incidentally found T2 gallbladder cancer

Sequential extended cholecystectomy (SEC) is currently recommended for gallbladder cancer (GBC) stage T2 and higher incidentally found after simple cholecystectomy (SC), but the value, timing and extent of re-resection has not been fully studied. This study evaluated long-term oncologic outcomes according to the type of surgery and time interval from initial cholecystectomy to SEC. Patients diagnosed with T2 GBC who underwent extended cholecystectomy (EC), SEC or SC between 2002 and 2017 were retrospectively reviewed. In 226 patients diagnosed with T2 GBC, 173, 44, and 53 patients underwent EC, SEC, and SC, respectively. Age, ASA performance score was higher in the SC group than EC and SEC groups combined. Five-year overall survival (OS) was 73.2%, 78.7%, and 50.1%, and disease-free survival (DFS) was 66.3%, 65.2%, and 46.8% for EC, SEC, and SC patients, respectively. OS and DFS were higher in EC than SC (p = 0.007 and p = 0.001), higher in SEC than SC (p = 0.001 and p = 0.065), but similar between EC and SEC (p = 0.909 and p = 0.722). SEC patients who underwent SEC ≤ 30 days after initial cholecystectomy had longer DFS than the > 30 days group (114 months vs. 71 months; p = 0.023). Recurrence pattern (local or distant) of SC vs. EC and SEC combined showed significant difference, but not between EC and SEC. Seventeen of 18 SC recur patients had distant metastasis at the time of recurrence. SEC is recommended for incidental T2 GBC because SEC provides better survival outcomes than SC alone. A time interval of ≤ 30 days between initial cholecystectomy and SEC is recommended.

Clinical Benefit of Depth of Response for Relapsed/Refractory Multiple Myeloma Patients Treated on Clinical Trials: Retrospective Analysis from Two Tertiary Centres

BackgroundData from clinical trials advance clinical practice, and inform treatment decisions, however trial populations may differ from real life patients. In multiple myeloma (MM), prognostic factors such as depth of response, genetic lesions, and ISS have been established largely from prospective clinical trial cohorts, and confirmation from real world data is important. Patients treated at later lines have reduced disease free and overall survival, but the importance of depth of response in relation to this remains unclear in the real world. A recent study in 7 European countries reported that depth of response correlated with longer disease free survival, however, this used physician judged disease responses1.AimsThe aim of our study was to assess the real world outcomes of relapsed/refractory (RR) MM patients treated on clinical trials where IMWG disease responses were used, in order to confirm the clinical benefit of response depth, and other prognostic indicators. We assessed time to next treatment (TTNT) and overall survival (OS) as parameters of benefit.MethodsPatients with RRMM treated on clinical trials at University College London (UCLH) and the National University Hospital (NUH) Singapore were identified from trial databases. Where patients were treated on more than 1 trial, the most recent was used. Patient and disease parameters were collated from clinical records and adverse risk FISH was defined as del17p, t(4;14), t1(4;16), t(14;20) or 1q gain. Survival was assessed by Kaplan-Meier methods and influence of individual factors by Cox-regression modelling on SPSS software. Survival was estimated from the day 1 of trial entry until event (date commenced next line or date of death, or date last seen if neither for TTNT and OS).ResultsBetween 2009-2016, 139 patients (UCLH, 99, NUH, 40) were treated on 14 clinical trials (9 phase 3, 3 phase 2). Median age was 64years (43-78), 29 patients were >70, 87 (62.6%) were male. Median prior lines of therapy was 2 (range 1 - 6, 44.6% had 1 prior line). Of 124 patients with ISS data, 51.6% were ISS 1. Of 100 patients with FISH results, 53 had adverse risk [del17p, 23 and t(4;14), 15], 18 patients had >1 high risk lesion. A range of investigational agents was used including monoclonal antibodies, 2nd and 3rd generation proteasome inhibitors and immunomodulatory drugs, and HDAC inhibitors.Overall response rate (ORR = CR/VGPR/PR) was 73.7%; 15 patients (10.9%) achieved sCR/CR, 32 (23.4%) VGPR and 54 (39.4%) PR. ORR did not differ between sites (UCLH 74.4%, NUH 71.1%), but was higher in patients with 1 prior line (90.3%, p=0.002), as was ³VGPR (50.0%, p=0.03). With a median follow up of 17.0 months, TTNT is 13.3months (11.2-15.5months), and OS 29.9months (15.7-43.1months); 72 patients have died.TTNT was longer in patients with ISS 1 (p£0.01 cf ISS 2/3), and with deeper responses (sCR/CR cf PR or MR/SD, p£0.02 for both). While adverse genetics did not correlate with TTNT, t(4;14) or ≥2 adverse risk markers was associated with shorter TTNT (p£0.01 both). Increasing lines of prior therapy correlated with shorter TTNT (p<0.001).OS was also longer in patients with ISS 1 (p<0.001 cf ISS 2/3, Figure 1), but reduced with increasing prior lines and in patients with t(4;14) (p<0.001 both). Deeper response was associated with stepwise increase in OS (sCR/CR cf SD/MR, p<0.001, Figure 2).Multivariate models for TTNT and OS included ISS, depth of response and number of prior lines of therapy. ISS retained independent significance for both (p<0.001). There was a trend of stepwise improvement for both TTNT and OS with deeper responses (p<0.02 for both). The number of prior lines of therapy was no longer associated with TTNT or OS.ConclusionOur results confirm that in RRMM patients on clinical trials, depth of response is an important end-point with meaningful impact on disease free and overall survival. ISS stage at relapse continues to be a clinically useful prognostic marker, and should be included in patient assessment. The influence of genetic risk in patients treated on clinical trials may be less clear in this era of rapidly developing treatments where some adverse features may be overcome by new drug classes.Reference:1. Yong, K et al. (2016). Multiple myeloma: patient outcomes in real-world practice. British Journal of Haematology, 175(2), 252-264. http://doi.org/10.1111/bjh.14213 [Display omitted] DisclosuresPopat:Celgene: Honoraria, Other: Travel support for meetings; Takeda: Honoraria, Other: Travel support for meetings; Amgen: Honoraria; Janssen: Honoraria, Other: Travel support for meetings. Rabin:Janssen: Consultancy, Other: Travel support for meetings, Speakers Bureau; Takeda: Consultancy, Other: Travel support for meetings, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Chng:Janssen China R&D: Research Funding. Yong:Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.

Mammographic density and prognosis in primary breast cancer patients

PurposeMammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. MethodsA total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. ResultsAfter median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. ConclusionsAlthough MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.

Artificial intelligence (AI)–powered pathologic response (PathR) assessment of resection specimens after neoadjuvant atezolizumab in patients with non-small cell lung cancer: Results from the LCMC3 study.

106 Background: PathR is an efficacy endpoint in Phase II and III neoadjuvant trials and is proposed as a surrogate for disease-free survival (DFS) and overall survival. Machine learning (ML)–based, automated approaches standardize quantification of areas of tumor bed and residual viable tumor. Here we show that automation may provide a scalable alternative to or complementary tool for manual assessment. Methods: We determined inter-reader variability for PathR among pathologists in the LCMC3 (NCT02927301) study and developed an AI-powered digital PathR assessment tool in line with manual consensus recommendations. Study cases were reviewed for PathR by a local site pathologist and 3 central expert pathologists (n = 127). When determined manually, major PathR (MPR) was defined as ≤10% viable tumor averaged per case. ML models were trained and validated by the PathAI research platform using digitized H&amp;E-stained tumor sections. The digital PathR model predicted percent viable tumor for each case as the sum of the cancer epithelium area from each slide divided by the sum of tumor bed area for each slide. DFS (clinical cutoff: Oct 23, 2020) was reported for patients with manual and digital PathR assessment (n = 135). For digital MPR, we used a prevalence-matched cutoff that maintained the same proportion of patients as manual MPR. Results: Inter-reader agreement among 1 local and 3 central pathologists for manual PathR was good (n = 127; ICC = 0.87; 95% CI: 0.84-0.90). Agreement was 91% (κ = 0.82) on manual MPR and 98% (κ = 0.88) on pathologic complete response (pCR). 6 patients had unanimous pCR. Digital and manual PathR were strongly correlated (n = 135, Pearson r = 0.78) and digital PathR demonstrated an outstanding predictability for manual MPR (AUROC = 0.975). The range was 0%-60% for digital PathR and 0%-100% for manual PathR with a regression line slope &lt; 1.0 (m = 0.303) indicating systematic differences between the methods, consistent with digital PathR using a high-resolution segmentation of cancer epithelium from stroma across each slide. Longer DFS was observed for MPR yes vs no with both digital and manual assessment (Table). Conclusions: This analysis showed good inter-reader agreement for manual and strong correlation of AI-powered digital and manual PathR. Comparable DFS rates for manual MPR and digital MPR are encouraging in the preliminary data. These data support further studies of digital PathR as a standardized and scalable tool to determine PathR. Clinical trial information: NCT02927301. [Table: see text]

Improving differential diagnosis of pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer via a transcriptomic, biological pathway-based ridge regression model.

3065 Background: In clinics, it can be challenging to make correct diagnosis of LCNEC, Small cell lung cancer (SCLC), if tissues, like needle biopsies, are insufficient or morphology was poorly preserved. In this study, a reliable classifier was constructed based on transcriptome data and machine learning (Ridge regression) to improve the diagnostic accuracy for LCNEC and SCLC. Methods: RNA-Seq data obtained from 3 public cohorts were collected as training set, including 60 NSCLC cases from The Cancer Genome Atlas (TCGA), 66 LCNEC cases from Julie George et al., Nature Communications 2018, and 33 SCLC cases from Julie George et al., Nature 2015. Another 80 NSCLC, 30 LCNEC and 15 SCLC cases published by Martin Peifer et al., Nature Genetics 2012 were used as validation set. Additionally, RNA-Seq data of 27 borderline samples which were hard to make diagnosis based on histology and Immunohistochemistry were used to test the accuracy of the prediction model. Results: 13,959 genes mapped to 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were included. Gene Set Variation Analysis (GSVA) algorithm was used to enrich and score each KEGG pathway. A prediction model based on GSVA score of each pathway was constructed via Ridge regression. This GSVA Score Model achieved ROC-AUC 0.949 and concordant rate of 0.75 for the entire prediction efficiency. Of the 27 borderline samples which were hard to make confirmed diagnosis, 17/27 (63.0%) were predicted as LCNEC, 7/27 were predicted as SCLC, and the remainder were predicted as NSCLC. While only 8 (29.6%) cases with LCNEC were diagnosed by pathologists, which was significantly lower than the results predicted by the model. Furthermore, cases with model predicted LCNEC had a significant longer disease-free survival than that with model predicted SCLC (median DFS,59 months for LCNEC vs 5 months for SCLC, p = 0.0043), which was in parallel with currently known prognostic difference of these two types of neuroendocrine tumors. Conclusions: This GSVA algorithm-based prediction model was able to make accurate diagnosis of LCNEC and SCLC. And it may provide valuable information for clinics to choose optimal therapeutic approach for patients with pulmonary neuroendocrine tumors.[Table: see text]

Feasibility and Long-Term Efficacy of PEComa Treatment-20 Years of Experience.

Perivascular epithelioid cell tumors (PEComas) represent a family of rare mesenchymal neoplasms, some of which are malignant. There are no specific management guidelines for PEComas, and factors correlating with the disease course are not well defined. This analysis aimed to describe the outcomes of PEComa patients treated radically, including those treated exclusively in the national reference sarcoma center. The secondary aim of the study was to analyze factors associated with PEComa treatment efficacy. We performed an analysis of 27 patients subsequently treated radically for PEComa between 1999 and 2019 who were in follow-up in the national sarcoma reference center. The proportional-hazards model was used to compare the risk of death. The median age at diagnosis was 45 (21–67) years, and 67% of patients were female. The median follow-up period was 68 months (95% CI: 39–101). At the time of analysis, eleven patients (40.7%) experienced progression of the disease and four (14.8%) died. Surgery in the reference sarcoma center was associated with a longer disease control (log-rank p < 0.001). The 5-year-OS rate was 88% (95% CI: 74–100) for the whole analyzed group. We concluded that PEComa treatment should be managed in reference sarcoma centers by a multidisciplinary tumor board with an experienced surgical team. Microscopically radical resection is associated with a longer disease-free survival. Patients requiring long-term follow-ups as late recurrence may be expected.

Prediction of prognosis of patients with lung cancer in combination with the immune score.

Purpose: The host’s immune response to malignant tumor is fundamental to tumorigenesis and tumor development. The immune score is currently used to assess prognosis and to guide immunotherapy; however, its association with lung cancer prognosis is not clear.Methods: Clinical features and immune score data of lung cancer patients from The Cancer Genome Atlas were obtained to build a clinical prognosis nomogram. The model’s accuracy was verified by calibration curves.Results: In total, 1005 patients with lung cancer were included. Patients were divided into three groups according to low, medium, and high immune scores. Compared with patients in the low immune score group, the disease-free survival (DFS) of patients in medium and high immune score groups was significantly longer; the hazard ratio (HR) and 95% confidence interval (95% CI) were 0.77 [0.60–0.99] and 0.74 [0.60–0.91], respectively. The overall survival (OS) of patients in the medium and high immune score groups was significantly longer than in the low immune score group; the HR and 95% CI were 0.74 [0.57–0.96] and 0.69 [0.55–0.88], respectively. A clinical prediction model was established to predict the survival prognosis. As verified by calibration curves, the model showed good predictive ability, especially for predicting 3-/5-year DFS and OS.Conclusion: Patients with lung cancer with medium and high immune scores had longer DFS and OS than those in low immune score group. Patient prognosis can be effectively predicted by the clinical prediction model combining clinical features and immune score and was consistent with actual clinical outcomes.

Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma: a multicentre randomised phase II trial (NCCTG N0849 [Alliance

Aimreport primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. MethodsIn this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). ResultsOf 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). ConclusionsAdding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

Cancer Cell B7-H3 Expression Is More Prevalent in the Pancreato-Biliary Subtype of Ampullary Cancer Than in Pancreatic Cancer

B7-H3 is an immunomodulatory member of the B7-superfamily with limited expression in normal tissues, but overexpression in several types of cancer. Therefore it is currently being explored as a potential target for cancer immunotherapy. The biological relevance of B7-H3 expression in pancreatic cancer is unclear, while there are no data on B7-H3 expression in ampullary cancer. We aimed to compare intra-tumoral B7-H3 expression between these two closely related cancer types and analyze its association with post-surgical disease course. B7-H3 expression levels were determined by immunohistochemistry in tissue microarrays of resected tumors of 137 pancreatic cancer patients and 83 patients with ampullary cancer of the pancreato-biliary subtype. B7-H3 was more frequently expressed in cancer cells of ampullary cancer patients compared to pancreatic cancer patients (51% versus 21%; p< 0.001). In ampullary cancer patients, but not in pancreatic cancer patients, B7-H3 cancer cell expression was associated with longer disease-free survival and patient survival. However, the prognostic value of B7-H3 was lost upon adjustment for CA19-9 levels. The frequencies of B7-H3 expression in tumor stroma did not differ between the two types of cancer (66% versus 63%). In both cancer types, stromal B7-H3 expression was not associated with post-surgical disease course. Compared to pancreatic cancer, B7-H3 is more frequently expressed in cancer cells of patients with the pancreato-biliary subtype of ampullary cancer. These data suggest that B7-H3 may represent an interesting potential target for immunotherapy in ampullary cancer rather than in pancreatic cancer.

Prognostic Nutritional Index (PNI) in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy as a Useful Prognostic Indicator.

ObjectivePrognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).MethodsA total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (<51) and a high PNI group (≥51). The associations between breast cancer and clinicopathological variables by PNI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC).ResultsThe results indicated that PNI had prognostic significance by an optimal cutoff value of 51 on DFS and OS in univariate and multivariate Cox regression survival analyses. Breast cancer patients with a high PNI value had longer DFS and OS than those with a low PNI value [47.64 vs. 36.60 months, P < 0.0001, hazard ratio (HR) = 0.264, 95%CI = 0.160–0.435; 73.61 vs. 64.97 months, P < 0.0001, HR = 0.319, 95%CI = 0.207–0.491, respectively]. Furthermore, the results indicated that patients with high PNI had longer DFS and OS than those with low PNI in early stage and advanced breast cancer, especially in advanced breast cancer. The mean DFS and OS times for breast cancer patients with high PNI by the log-rank test were longer than in those with low PNI in different molecular subtypes. Moreover, the mean DFS and OS times in patients with high PNI by the log-rank test were longer than in those patients with low PNI without or with lymph vessel invasion. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the PNI had no significance on the toxicities of all enrolled patients, except in anemia, leukopenia, and myelosuppression.ConclusionPretreatment PNI with the advantages of being convenient, noninvasive, and reproducible was a useful prognostic indicator for breast cancer patients receiving neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

A highly expressed mRNA signature for predicting survival in patients with stage I/II non-small-cell lung cancer after operation

There is an urgent need to identify novel biomarkers that predict the prognosis of patients with NSCLC. In this study,we aim to find out mRNA signature closely related to the prognosis of NSCLC by new algorithm of bioinformatics. Identification of highly expressed mRNA in stage I/II patients with NSCLC was performed with the “Limma” package of R software. Survival analysis of patients with different mRNA expression levels was subsequently calculated by Cox regression analysis, and a multi-RNA signature was obtained by using the training set. Kaplan–Meier estimator, log-rank test and receiver operating characteristic (ROC) curves were used to analyse the predictive ability of the multi-RNA signature. RT-PCR used to verify the expression of the multi-RNA signature, and Westernblot used to verify the expression of proteins related to the multi-RNA signature. We identified fifteen survival-related mRNAs in the training set and classified the patients as high risk or low risk. NSCLC patients with low risk scores had longer disease-free survival than patients with high risk scores. The fifteen-mRNA signature was an independent prognostic factor, as shown by the ROC curve. ROC curve also showed that the combined model of the fifteen-mRNA signature and tumour stage had higher precision than stage alone. The expression of fifteen mRNAs and related proteins were higher in stage II NSCLC than in stage I NSCLC. Multi-gene expression profiles provide a moderate prognostic tool for NSCLC patients with stage I/II disease.

Influences on pathologic complete response in breast cancer patients after neoadjuvant chemotherapy

PurposePathologic complete response is associated with longer disease-free survival and better overall survival after neoadjuvant chemotherapy in breast cancer patients. We, therefore, evaluated factors influencing pathologic complete response.MethodsPatients receiving neoadjuvant chemotherapy from 2015 to 2018 at the Saarland University Hospital were included. Patients’ age, tumor stage, tumor biology, genetic mutation, recurrent cancer, discontinuation of chemotherapy, and participation in clinical trials were extracted from electronic medical records. Binary logistic regression was performed to evaluate the influence of these factors on pathologic complete response.ResultsData of 183 patients were included. The median patient’s age was 54 years (22–78). The median interval between diagnosis and onset of chemotherapy was 28 days (14–91); between end of chemotherapy and surgery 28 days (9–57). Sixty-two patients (34%) participated in clinical trials for chemotherapy. A total of 86 patients (47%) achieved pathologic complete response. Patient’s age, genetic mutation, recurrent cancers, or discontinuation of chemotherapy (due to side effects) and time intervals (between diagnosis and onset of chemotherapy, as well as between end of chemotherapy and surgery) did not influence pathologic complete response. Patients with high Ki67, high grading, Her2 positive tumors, as well as patients participating in clinical trials for chemotherapy had a higher chance of having pathologic complete response. Patients with Luminal B tumors had a lower chance for pathologic complete response.ConclusionParticularly patients with high risk cancer and patients, participating in clinical trials benefit most from chemotherapy. Therefore, breast cancer patients can be encouraged to participate in clinical trials for chemotherapy.

The Role of Chemotherapy in Patients With HER2-Negative Isolated Locoregional Recurrence of Breast Cancer: A Multicenter Retrospective Cohort Study.

Background: The role of chemotherapy for isolated locoregional recurrence (iLRR) of breast cancer has not been firmly established after local therapies.Methods: We performed a multicenter, retrospective analysis to evaluate the clinical implications of chemotherapy in breast cancer patients with HER2-negative iLRR.Results: Of a total of 277 patients, 146 (52.7%) received chemotherapy for iLRR. Median follow-up duration was 56.1 months. Eighty-six (31.0%) patients had luminal B-like and 100 (36.1%) had TNBC iLRR. There was a trend of longer disease free survival (DFS) in the chemotherapy group (4-year DFS: 70.4 vs. 59.5%, HR = 0.68, 95% CI 0.45–1.02, log-rank p = 0.059). When adjusted with clinically relevant factors, DFS was significantly prolonged with chemotherapy (adjusted HR = 0.61, 95% CI 0.40–0.94, p = 0.023). Subgroup analyses for DFS showed patients with disease free interval (DFI) <5 years or prior chemotherapy had a benefit from chemotherapy (adjusted HR = 0.57, p = 0.018; adjusted HR = 0.51, p = 0.005, respectively). Regarding the molecular subtypes, a longer DFS with chemotherapy was observed both in luminal B-like (4-year DFS: 77.8 vs. 55.0%, HR = 0.51, 95% CI 0.27–0.99, log-rank p = 0.048) and in TNBC patients (4-year DFS: 61.9 vs. 42.8%, HR = 0.49, 95% CI 0.24–1.02, log-rank p = 0.056), but not in luminal A-like.Conclusions: The chemotherapy for iLRR of breast cancer should be individualized for each patient, considering DFI, prior chemotherapy, and molecular subtypes.

Prognostic value of the preoperative lymphocyte-to-monocyte ratio for survival after lung cancer surgery

BackgroundThe aim of this study was to assess the effect of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on overall survival and disease-free survival in patients with lung cancer treated with radical surgery.MethodsWe performed a retrospective review of patients with lung cancer who prospectively underwent radical resection between 2004 and 2012. Blood samples were taken as part of the preoperative workup. The inflammatory markers studied were absolute values of lymphocytes, monocytes, neutrophils and platelets, with subsequent calculation of ratios. Median follow-up was 52 months.ResultsTwo hundred and sixty-eight patients underwent surgery, of whom 218 (81.3%) were men. Mean age was 62.9 ± 8.7 years. A lymphocyte-to-monocyte ratio ≥ 2.5 was independently associated with longer disease-free survival (hazard ratio [HR] 0.476 (0.307–0.738), p = 0.001) and longer overall survival (HR, 0.546; 95% CI: 0.352–0.846; p = 0.007), in models adjusted for age, sex, stage, and type of resection. No other systemic inflammatory marker showed a significant association.ConclusionPreoperative LMR is an independent prognostic factor of overall survival and recurrence-free survival in patients with surgically-resected early stage lung cancer.

Effects of Metformin and Vitamin D on Clinical Outcome in Cholangiocarcinoma Patients

Background and Aims: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. Methods: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. Results: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32–0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52–0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26–0.73, p = 0.0016). Conclusions: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinoma patients. We are planning to undertake a prospective study to validate these data.

Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients.

Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ≥ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort. Results: in the training cohort, 100 Stage II–III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4+ intratumoral T-cells (aHR [100 cell/mm2 increase] 0.98, 95%CI 0.95–1.00, p = 0.041) and CD163+ inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8+ T-cells and CD68+ macrophages as compared to those with low density of both intratumoral CD8+ T-cells and CD68+ macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8+ and CD3+ T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, p < 0.001) and those with high density of both intratumoral CD8+ and CD68+ were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, p = 0.025). Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages distribution in melanomas may predict the risk of recurrence and death with potential implications for the stratification of stage II–III melanoma patients.