A Case of Secretory Carcinoma in a Patient With a History of Contralateral Medullary Carcinoma

Background: Secretory and medullary carcinomas of the breast are rare subtypes of infiltrating ductal carcinoma. The different histological behavior of medullary and secretory carcinomas is correlated with different imaging features on mammography, ultrasound, and magnetic resonance imaging. Case Report: We report the case of a Caucasian woman in which both subtypes of tumors were diagnosed in an 8-year time interval and evaluate, in antithesis, histopathological and imaging aspects of medullary and secretory carcinoma. Conclusion: To our knowledge, this is the first case reported in literature of secretory carcinoma with a complete imaging tumor evaluation in a patient with a previous contralateral medullary cancer.

Immune-related Thyroid Dysfunction (irTD) in Non-small Cell Lung Cancer (NSCLC) Correlates With Response and Survival

Background: There is no clear information on the proportion of patients who need therapy for immune-related thyroid dysfunction (irTD) or who need to delay, omit, or discontinue immunotherapy. Furthermore, it is not well known whether irTD correlates with better outcomes or not. Patients and Methods: We conducted a retrospective study in patients with metastatic non-small cell lung cancer (NSCLC) treated with anti-PD1 or anti-PD-L1. Results: Our study enrolled 75 patients, 25.3% of them developed immune-related thyroid dysfunction. Three patients delayed a course of immunotherapy due to irTD, 2 patients omitted a course and 1 patient permanently discontinued. In patients with irTD compared with those without irTD the ORR was 42.1% vs. 7.1% (p<0.001), DCR was 78.9% vs. 32.1% (p<0.001); mPFS was 15.7 vs. 3.6 months (p<0.001) and mOS was 18.6 months vs. 5.1 months (p<0.001). Conclusion: Immune-related thyroid dysfunction has a mild impact on the immunotherapy treatment program. The occurrence of irTD correlates with more favorable response and survival.

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma

Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. Patients and Methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (rPearson=0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.

Age-related Survival Outcomes for Pancreatic Cancer by Age

Background/Aim: Pancreatic cancer has a very poor prognosis, though outcomes based on age are not well characterized. The aim of current study was to analyze the survival of patients with pancreatic cancer based on age. Patients and Methods: Using National Cancer Data Base (NCDB), we determined survival outcome based on age among patients with pancreatic cancer. Results: A total of 423,482 patients between 2004 and 2017 were included in the study. Patients aged between 18 and 40-years-old had the worst 3-year survival rate among stage 1 disease. Conversely, patients over 65-years-old had the worst 3-year survival rate and presented with more advanced disease (clinical stages 3 and 4). Conclusion: Older patients with more advanced disease had worse survival.

Inflammation-based Indexes Upon Adjuvant Chemotherapy Initiation as a Predictor of Relapse After Curative Resection of Colorectal Cancer With an Oxaliplatin-based Regimen

Background/Aim: We investigated the clinical efficacy of inflammation-based indexes in predicting unfavourable relapse-free survival (RFS) in patients with stage II/III colorectal cancer (CRC) receiving oxaliplatin-based adjuvant chemotherapy. Patients and Methods: A retrospective analysis was performed on 45 patients who underwent curative resection for stage II/III CRC followed by oxaliplatin-based adjuvant chemotherapy after 8 weeks. Upon adjuvant chemotherapy initiation, all patients were evaluated for lymphocyte count (LC), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS) and prognostic nutritional index (PNI), after which their correlation with relapse was analysed. Results: Univariate analysis identified LC <1,350/mm3, NLR ≥2.03, LMR <5.15, PLR ≥209, mGPS 2, and early discontinuation of chemotherapy within two months as significant risk factors for RFS. Multivariate analysis identified LMR <5.15, PLR > 209 and mGPS 2 as significant independent risk factors for unfavourable RFS. Conclusion: Measurement of LMR, PLR, and mGPS upon adjuvant therapy initiation can be a useful tool for predicting recurrence after curative surgery for stage II/III CRC.

Improvement of Medical Treatment in Japanese Patients With Metastatic Renal Cell Carcinoma

Background/Aim: To evaluate the relationship between treatment period and overall survival (OS) and to identify clinical factors associated with OS in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Two hundred thirteen consecutive patients with mRCC receiving systemic therapy between 2008 and 2020 were divided into two groups: those starting first-line therapy in 2008-2015 (n=133) and those in 2016-2020 (n=80). Clinical factors associated with OS were retrospectively and statistically analyzed. Results: Median OS and one-, three- and five-year OS rates were not reached and 88.7%, 64.9%, and 64.9% in patients treated in 2016-2020; 31.4 months and 78.5%, 42.8% and 34.2% in 2008-2015 (p=0.0013). Multivariate analysis identified the period in which first-line therapy was started as the strongest predictor for OS (p=0.0002). Conclusion: OS was significantly better in mRCC patients treated in 2016-2020 than in 2008-2015. Treatment period was the strongest predictor for OS.

FOLFIRINOX as First-line Chemotherapy in Japanese Patients Suffering from Metastatic Pancreatic Cancer (KOBE FOLFIRINOX Study)

Background/Aim: FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) combination chemotherapy is the gold-standard therapy for advanced pancreatic cancer. In this study, FOLFIRINOX dosages for Japanese patients were established enabling FOLFIRINOX therapy optimization for efficient use. Patients and Methods: Patients with advanced pancreatic cancer were treated with varying doses of FOLFIRINOX to determine the optimum dosage for highest remission outcomes with the least post-chemotherapy toxicities. Results: Patients given 180 mg of irinotecan and a 400 mg bolus of 5-fluorouracil (5-FU) showed a marked difference in outcome when compared to irinotecan 180 mg given without the 5-FU bolus, with the overall response rate being 28%, a survival time of 6.4 months and progression-free survival time of 4.5 months. Conclusion: The optimum dose of FOLFIRINOX was a dosage combination of oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, l-leucovorin 400 mg/m2 and 5-FU 2,400 mg/m2, administered as a continuous 46-h infusion.

Preoperative Predictors of Lymph Node Invasion and Biochemical Recurrence in High-risk Prostate Cancer

Aim: To evaluate the preoperative predictors of pathological lymph node (LN) metastasis and prognostic factors for postoperative biochemical recurrence (BCR) in robot-assisted radical prostatectomy with extended pelvic LN dissection in patients with D'Amico high-risk prostate cancer (PCa). Patients and Methods: Overall, 107 patients with D'Amico high-risk PCa underwent robot-assisted radical prostatectomy with extended pelvic LN dissection without neoadjuvant or adjuvant therapy. BCR was defined as a prostate-specific antigen (PSA) level ≥0.2 ng/ml. Moreover, BCR-free survival rates were determined using Kaplan-Meier analysis. Logistic regression analysis was used to evaluate preoperative predictors of pathological LN metastasis. Cox regression analysis was used to evaluate the effects of preoperative and pathologic variables on BCR. Results: The median follow-up was 21 months, and the 5-year BCR-free survival rate was 59.8%. The positive LN rate was 21.5%. In multivariate analysis, the percentage of positive cores was a significant preoperative predictor of positive LNs. Patients with >50% positive cores (p=0.004) and PSA density (PSAD) >0.5 ng/ml/cc (p=0.005) had a high risk of having ≥3 positive LNs. In multivariate analysis, PSAD >0.5% was a significant preoperative predictor of BCR. Among the postoperative predictors, the number of positive LNs was significantly associated with BCR. Patients with ≥3 positive LNs (n=7) had significantly lower BCR-free survival rates than patients with one or two positive LNs (n=16) (p<0.001). Patients with >50% positive cores and PSAD >0.5 ng/ml/cc had a risk for a high number of positive LNs (≥3) that was strongly associated with shorter BCR-free survival (p<0.001). Conclusion: The percentage of positive cores may be useful as a preoperative predictor of pathological LN metastasis in patients with high-risk PCa. Patients with >50% positive cores and PSAD >0.5 ng/ml/cc were found to have a high risk for ≥3 positive LNs and shorter BCR-free survival.

Complete Response of a Mutated BRCA2 Metastatic Clear Cell Endometrial Adenocarcinoma to the Poly (ADP ribose) Polymerase (PARP) Inhibitor Olaparib

Background: Cancer of the endometrium is the most common gynecologic malignancy in developed countries and the second most common in developing countries. Endometrioid tumors tend to have a favorable prognosis and typically present at an early stage with abnormal uterine bleeding. Clear cell carcinoma as well as serous endometrial carcinoma are associated with a poorer prognosis. Patients with metastatic endometrial cancer are treated with systemic therapy either following surgery or as primary therapy. As far as second-line chemotherapy is concerned, there are no general agreements on the chemotherapy to be used. Furthermore, to the best of knowledge, there are no studies on the use of poly (ADP ribose) polymerase (PARP) inhibitors in endometrial cancer even in BRCA mutated tumors. Case Report: We here present the case report of an 81-year-old woman with a mutated BRCA2 metastatic clear cell endometrial adenocarcinoma that showed an excellent clinical and radiological response to the PARP inhibitor olaparib. Conclusion: Olaparib could be successfully used in this patient setting.

Impact of Ubiquitination Signaling Pathway Modifications on Oral Carcinoma

Among intra-cellular homeostasis mechanisms, ubiquitination plays a critical role in protein metabolism regulation by degrading proteins via activating a broad spectrum of ubiquitin chains. In fact, ubiquitination and sumoylation signaling pathways are characterized by increased complexity regarding the molecules and their interactions. The Ubiquitin-Proteasome System (Ub-PS) recognizes and targets a broad spectrum of protein substrates. Ubiquitin conjugation modifies each substrate protein determining its biochemical fate (degradation). A major functional activity of Ub-PS is autophagy mechanism regulation. Interestingly, Ub-PS promotesall stages of bulk autophagy (initiation, execution, and termination). Autophagy is a crucial catabolic process that provides protein degradation and for this reason the interaction with Ub-PS is crucial. Furthermore, ubiquitination controls and regulates specific types of protein targets. Ub-PS is also involved in oxidative cellular stress and DNA damage response. Additionally, the functional role of Ub-PS in ribosome machinery regulation seems to be crucial. Concerning carcinogenesis, Ub-PS is involved in malignant disease development and progression by negatively affecting the corresponding TGF-B-, MEEK/MAPK/ERK-JNK- dependent signaling pathways. In the current review article, we describe the role of Ub-PSbiochemicalmodifications and alterations in oral squamous cell carcinoma (OSCC).