Non-metastatic Patients Research Articles

Abstract P4-06-12: Decision of Neoadjuvant Therapy in Younger vs. Older Breast Cancer Patients: A Real-World Data Analysis

Abstract Background: The incidence of breast cancer among younger patients (age ≤ 40) is higher in Latin America than in other regions. The multidisciplinary approach of breast cancer cases has been related with better survival, and the knowledge about specific clinicopathological features of this population is needed to optimize the therapeutic approach. The aim of our study was to describe the clinicopathological characteristics of breast cancer in younger (Y) compared with older patients (O), and to determine which characteristics were associated with the use of primary systemic therapy. Methods: A retrospective cohort study was designed. Clinicopathological data of consecutive invasive non-metastatic breast cancer patients diagnosed between Jan 2015 to Dec 2019 in two private oncological centers in Lima, Perú were collected. Logistic regression analysis was performed to obtain models to predict primary systemic therapy as first treatment. Results: We included 503 cases (mean age 49.8 years [SD 11.8]), 30.6% younger (n = 109) and 69.4% O (n = 394). No significant differences were found for ductal histology (89% Y vs. 87.7% O, p = 0.49) and HER2-overexpression (28.4% Y vs. 23.9% O, p = 0.39). Significant differences were found for stage III (37.6% Y vs. 20% O, p < 0.01), grade 3 (44.4% Y vs 33% O, p = 0.04) and HR-positive (64.2% Y vs. 75.1% O, p = 0.03). Univariate analysis showed significant OR = 2.1 to receive primary systemic therapy for Y (95%CI 1.37 – 3.24; p < 0.01), however, multivariate analysis adjusted for age, hormone receptors (HR), HER2, grade and stage showed non-significant OR = 1.5 to receive primary systemic therapy for Y (95%CI 0.90 – 2.50; p = 0.12) as detailed in the table below: Conclusions: In our series we found a greater proportion of young breast cancer patients than previously reported. Clinical-pathological characteristics of breast cancer were different between younger and older patients, showing more aggressive phenotypes for younger patients with greater proportion of stage III, grade 3 and non-expression of hormone receptors. Decision of using primary systemic therapy in our series was based on anatomic and biologic characteristics and not on age. Citation Format: Enrique Alanya, Silvia Falcon-Lizaraso, Sebastian Aldecoa-Falcon, Franklin Aldecoa-Bedoya. Decision of Neoadjuvant Therapy in Younger vs. Older Breast Cancer Patients: A Real-World Data Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-12.

Technical options in surgery for artery-involving pancreatic cancer: Invasion depth matters

BackgroundThe artery involvement explains the majority of primary unresectability of non-metastatic pancreatic cancer patients and both arterial resection and artery-sparing dissection techniques are utilized in curative-intent pancreatectomies for artery-involving pancreatic cancer (ai-PC) patients. MethodsThis narrative review summarized the history of resectability evaluation for ai-PC and attempted to interpret its current pitfalls that led to the divergence of resectability prediction and surgical exploration, with a focus on the rationale and the surgical outcomes of the sub-adventitial divestment technique. ResultsThe circumferential involvement of artery by tumor currently defined the resectability of ai-PC but insufficient to preclude laparotomy with curative intent. The reasons behind could be: 1. The radiographic involvement of tumor to arterial circumference was not necessarily resulted in histopathological artery wall invasion; 2. the developed surgical techniques facilitated radical resection, better perioperative safety as well as oncological benefit. The feasibility of periadventitial dissection, sub-adventitial divestment and other artery-sparing techniques for ai-PC depended on the tumor invasion depth to the artery, i.e., whether the external elastic lamina (EEL) was invaded demonstrating a hallmark plane for sub-adventitial dissections. These techniques were reported to be complicated with preferable surgical outcomes comparing to arterial resection combined pancreatectomies, while the arterial resection combined pancreatectomies were considered performed in patients with more advanced disease. ConclusionsAdequate preoperative imaging modalities with which to evaluate the tumor invasion depth to the artery are to be developed. Survival benefits after these techniques remain to be proven, with more and higher-level clinical evidence needed. Key messageThe current resectability evaluation criteria, which were based on radiographic circumferential involvement of the artery by tumor, was insufficient to preclude curative-intent pancreatectomies for artery-involving pancreatic cancer patients. With oncological benefit to be further proven, periarterial dissection and arterial resection have different but overlapping indications, and predicting the tumor invasion depth in major arteries was critical for surgical planning.

Biliary tract cancers have distinct epidemiological patterns and clinical characteristics according to tumour site

BackgroundLittle is known about the epidemiology of biliary tract cancers over the last decade. We investigated trends in incidence, treatment and prognosis of biliary tract cancers according to anatomic site. Methods714 biliary tract cancers recorded between 2012 and 2019 in the French population-based cancer registry of Burgundy were included. Trends in world age-standardized incidence were depicted using Poisson regression. ResultsIntrahepatic cholangiocarcinoma accounted for 40% of biliary tract cancer. Half of the patients were older than 75 years at diagnosis. Incidence of biliary tract cancer did not vary over time, except a slight increase in intrahepatic cholangiocarcinoma in men and a decrease in the ampulla in both sexes. Among non-metastatic patients, the proportion who underwent R0 resection ranged from 15% for intrahepatic cholangiocarcinoma to 58% for ampulla cancer (p < 0.001). Age, performance status and hospital type were associated with resection. Among unresected patients, 45% received chemotherapy. Older age, jaundice, increasing performance status and comorbidities index negatively affected chemotherapy administration. Net survival was higher for ampulla than for other sites, regardless of patient and treatment characteristics. ConclusionBiliary tract cancers present different patterns in incidence. The ampulla site should be considered separately in clinical trials due to its better outcomes.

Achieving a Textbook Outcome in Colon Cancer Surgery Is Associated with Improved Long-Term Survival

Colon cancer surgery is a complex clinical pathway and traditional quality metrics may exhibit significant variability between hospitals and healthcare providers. The Textbook Outcome (TO) is a composite quality marker capturing the fraction of patients, in whom all desired short-term outcomes of care are realised. The aim of the present study was to assess the TO in a series of non-metastatic colon cancer patients treated with curative intent, with emphasis on long-term survival. Stage I-III colon cancer patients, who underwent curative colectomy following the Complete Mesocolic Excision principles, were retrospectively identified from the institutional database. TO was defined as (i) hospital survival, (ii) radical resection, (iii) no major complications, (iv) no reintervention, (v) no unplanned stoma and (vi) no prolonged hospital stay or readmission. In total, 128 patients (male 61%, female 39%, mean age 70.7 ± 11.4 years) were included in the final analysis. Overall, 60.2% achieved a TO. The highest rates were observed for "hospital survival" and "no unplanned stoma" (96.9% and 97.7%), while the lowest rates were for "no major complications" and "no prolonged hospital stay" (69.5% and 75%). Older age, left-sided resections and pT4 tumours were factors limiting the chances of a TO. The 5-year overall and 5-year cancer-specific survival were significantly better in the TO versus non-TO subgroup (81% vs. 59%, p = 0.009, and 86% vs. 65%, p = 0.02, respectively). Outcomes in colon cancer surgery may be affected by patient-, doctor- and hospital-related factors. TO represents those patients who achieve the optimal perioperative results, and is furthermore associated with improved long-term cancer survival.

The relationship between nutritional status before chemotherapy with nutritional status after chemotherapy in locoregionally advanced nasopharyngeal carcinoma patients

Background: Malnutrition in nasopharyngeal carcinoma (NPC) patients is caused by various factors such as tumor localization, metabolic derangement, and side effects of therapy. Poor nutritional status in cancer patients is associated with serious clinical consequences such as poor quality of life, higher treatment toxicity, and poor prognosis. The purpose of this study was to determine the effect of nutritional status before chemotherapy on the nutritional status after chemotherapy in non-metastatic advance-stage NPC patients. Methods: This study was an observational study with a cross sectional design using secondary data involving non-metastatic advanced-stage NPC patients undergoing chemotherapy at dr. Kariadi Hospital Semarang in January 2020 – June 2022. The sampling technique used was consecutive sampling. Nutritional status was measured by malnutrition criteria according to the American Society for Parenteral and Enteral Nutrition (ASPEN). Statistical analysis was performed with Chi-Square and McNemar analysis test. Results: Total sample of this study was 55 subjects. The results of this study were there was a relationship between nutritional status before chemotherapy and nutritional status after chemotherapy in non-metastatic advanced-stage NPC patients (P&lt;0.05). All subjects were malnourished before chemotherapy, with 12.7% moderately malnourished and 87.3% severely malnourished. All subjects were malnourished after chemotherapy, with 41.8% moderately malnourished and 58.2% severely malnourished, decreased nutritional status of post-chemotherapy non-metastatic advanced NPC patients was related to the length of chemotherapy (p&lt;0.05), but not related to comorbidities, age, and stage of chemotherapy (p&gt;0.05). Conclusion: There is a relationship between nutritional status before chemotherapy and nutritional status after chemotherapy in non-metastatic advanced-stage NPC patients.

A novel conditional survival nomogram for monitoring real-time prognosis of non-metastatic triple-negative breast cancer.

Conditional survival (CS) is defined as the possibility of further survival after patients have survived for several years since diagnosis. This may be highly valuable for real-time prognostic monitoring, especially when considering individualized factors. Such prediction tools were lacking for non-metastatic triple-negative breast cancer (TNBC). Therefore, this study estimated CS and developed a novel CS-nomogram for real-time prediction of 10-year survival. We recruited 32,836 non-metastatic TNBC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019), who were divided into training and validation groups according to a 7:3 ratio. The Kaplan-Meier method estimated overall survival (OS), and the CS was calculated using the formula CS(y|x) =OS(y+x)/OS(x), where OS(x) and OS(y+x) were the survival of x- and (x+y)-years, respectively. The least absolute shrinkage and selection operator (LASSO) regression identified predictors to develop the CS-nomogram. CS analysis reported gradual improvement in real-time survival over time since diagnosis, with 10-year OS updated annually from an initial 69.9% to 72.8%, 78.1%, 83.0%, 87.0%, 90.3%, 93.0%, 95.0%, 97.0%, and 98.9% (after 1-9 years of survival, respectively). The LASSO regression identified age, marriage, race, T status, N status, chemotherapy, surgery, and radiotherapy as predictors of CS-nomogram development. This model had a satisfactory predictive performance with a stable 10-year time-dependent area under the curves (AUCs) between 0.75 and 0.86. Survival of non-metastatic TNBC survivors improved dynamically and non-linearly with survival time. The study developed a CS-nomogram that provided more accurate prognostic data than traditional nomograms, aiding clinical decision-making and reducing patient anxiety.

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC). This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage. 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p< 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p<0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34). Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis

To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE

IntroductionInternational guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. MethodsThis prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. ResultsAmong 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. ConclusionTreatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.

HIDRATE-PRO: A prospective pilot study evaluating a digital behavioral health intervention to improve bladder-filling compliance in patients with prostate cancer receiving radiation.

70 Background: Prostate cancer (PCa) patients undergoing radiation therapy (RT) need comfortably full bladders during RT to reduce toxicities. Awareness of this state is lacking, and poor compliance is common with standard of care written/verbal instructions, leading to wasted patient value (PV) and inefficient throughput (TE). Herein, we assessed the feasibility and acceptability of a digital behavioral intervention (DBI) to improve bladder filling compliance, methods for quantifying PV, IT, and behavioral biomarkers. Methods: We enrolled 18 non-metastatic PCa patients in a prospective, single-arm pilot study using a DBI. The DBI consists of a smart water bottle and companion app that tracks water consumption. Additionally, visual alerts (water bottle glow and phone notifications) remind the patient to empty his bladder and drink a personalized volume goal (VG) at a set time. The VG is based on simulation bladder volume and reminders are initially set 1.25 hours prior to scheduled RT. Patients were trained to adjust their VG and notification times to achieve comfortably full bladders. Primary endpoint was met if qualitative (QLC) and quantitative compliance (QNC) were both &gt;80%. Other endpoints include acceptability assessed via Service User Technology Acceptability Questionnaire (SUTAQ), engagement (&gt;80% of patients used the device &gt; 50% of the time) and impact of DBI on PV and TE. For QLC, patients were asked if they prepared their bladders before daily RT. QNC was met if bladder volumes on daily CBCT were &gt; 75% of the simulation’s volume. The SUTAQ was given pre- and post-DBI. PV and TE were measured by time spent in clinic and on the linear accelerator (linac), respectively. Biometric data was probed for insights on optimal drinking behaviors. Results: All endpoints were met. QLC was 100% on 375/398 (94.2%) of total treatments, while QNC was 88.9% on 341/398 (85.7%) total treatments. Patients were accepting of DBI with few privacy concerns (4.33/5.00), believe in benefits (4.00/5.00), high satisfaction (4.56/5.00) and high usability (4.24/5.00). Most patients, 15/18 (83.3%), used the DBI on &gt;50% of treatments and met the engagement requirements. Patients with empty bladders (n=43) spent significantly more time (75.14 vs 50.59 minutes, p=0.007) in clinic than patients who came with full bladders (n=355). Similarly, these patients spent nearly twice as long on the linac (21.63 v 12.50 minutes, p&lt;0.001). Shorter time spent drinking correlated with empty bladders (17.07 vs 27.85 min, p=0.027). Conclusions: This digital intervention trial showed high rates of bladder filling compliance and engagement. High patient-value and throughput efficiency was feasibly quantified by shortened clinic times and linac usage, respectively. Future studies are needed to evaluate clinical outcomes, patient experience and cost benefit. Clinical trial information: NCT04946214 .

Ileal Conduit Versus Orthotopic Neobladder Urinary Diversion in Robot-assisted Radical Cystectomy: Results from a Multi-institutional Series

BackgroundHead-to-head comparisons between ileal conduit (IC) and orthotopic neobladder (ONB) in terms of peri- and postoperative outcomes and complications, in the specific setting of robot-assisted radical cystectomy (RARC), are not available. ObjectiveTo address the impact of the type of urinary diversion (UD, IC vs ONB) on RARC morbidity, as well as operative time (OT), length of stay (LOS), and readmissions. Design, setting, and participantsUrothelial bladder cancer patients treated with RARC at nine high-volume European institutions between 2008 and 2020 were identified. InterventionRARC with either IC or ONB. Outcome measurements and statistical analysisIntra- and postoperative complications were collected and reported according to the Intraoperative Complications Assessment and Reporting with Universal Standards recommendations and European Association of Urology guidelines, respectively. Multivariable logistic regression models tested the impact of UD on outcomes, after adjustment for clustering at single hospital level. Results and limitationsOverall, 555 nonmetastatic RARC patients were identified. In 280 (51%) and 275 (49%) patients, an IC and an ONB were performed, respectively. Eighteen intraoperative complications were recorded. The rates of intraoperative complications were 4% in IC patients and 3% in ONB patients (p = 0.4). The median LOS and readmission rates were 10 versus 12 d (p < 0.001) and 20% versus 21% (p = 0.8) in IC versus ONB patients, respectively. At a multivariable logistic regression analyses, the type of UD (IC vs ONB) reached the independent predictor status for prolonged OT (odds ratio [OR]: 0.61, p = 0.03) and prolonged LOS (OR: 0.34, p < 0.001), but not for readmission (OR: 0.92, p = 0.7). Overall, 513 postoperative complications were experienced by 324 patients (58%). At least one postoperative complication was experienced by 160 (57%) IC patients versus 164 (60%) ONB patients (p = 0.6). The type of UD reached the status of an independent predictor of UD-related complications (OR: 0.64, p = 0.03). ConclusionsCompared with RARC with ONB, RARC with IC is less prone to UD-related postoperative complications, prolonged OT, and prolonged LOS. Patient summaryTo date, the impact of the type of urinary diversion, namely, ileal conduit versus orthotopic neobladder, on peri- and postoperative outcomes of robot-assisted radical cystectomy is unknown. Based on a rigorous data accrual, which relied on established complication reporting systems (Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology recommended systems), we reported intra- and postoperative complications according to urinary diversion type. Moreover, we found that ileal conduit was associated with lower operative time and length of stay, and yielded a protective effect in terms of urinary diversion–related complications.

Upper-neck irradiation versus standard whole-neck irradiation in nasopharyngeal carcinoma: A systematic review and meta-analysis.

To evaluate the role of upper-neck irradiation versus standard whole-neck irradiation in patients with N0-1 nasopharyngeal carcinoma. We conducted a PRISMA guideline based systematic review and meta-analysis. Randomized clinical trials assessing upper-neck irradiation versus whole-neck irradiation with or without chemotherapy in non-metastatic N0-1 nasopharyngeal carcinoma patients were identified. The studies were searched on the PubMed, Embase and Cochrane library up to March 2022. Survival outcomes, including overall survival, distant metastasis-free survival and relapse-free survival, and toxicities rate were evaluated. There were two randomized clinical trials with 747 samples finally included. Upper-neck irradiation had similar overall survival (hazard ratio = 0.69, 95% confidence interval = 0.37-1.30), distant metastasis-free survival (hazard ratio = 0.92, 95% confidence interval = 0.53-1.60) and relapse-free survival (risk ratio = 1.03, 95% confidence interval = 0.69-1.55) compared to whole-neck irradiation. No differences in both acute and late toxicities were recorded between upper-neck irradiation and whole-neck irradiation. This meta-analysis supports the potential role of upper-neck irradiation in this population of patients. Further research is needed to confirm results.

Tumor deposits are associated with a higher risk of peritoneal disease in non-metastatic colorectal cancer patients.

Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients. A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage. A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31). In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HRcounterparts. Alternative strategies for surveillance and treatment should be considered.

CD8/PD-L1 immunohistochemical reactivity and gene alterations in cutaneous squamous cell carcinoma.

In recent years, several immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) or PD-1 have been developed for cancer therapy. The genetic background of tumors and factors that influence PD-L1 expression in tumor tissues are not yet elucidated in cutaneous squamous cell carcinoma (cSCC). CD8-positive tumor-infiltrating lymphocytes (TILs) are known to be related to tumor immunity. Here, we aimed to study the relationship between CD8/PD-L1 immunohistochemical reactivity and gene alterations in cSCC. Tumorigenic genes were examined to identify gene alterations using next-generation sequencing (NGS). We collected 27 cSCC tissue samples (from 13 metastatic and 14 non-metastatic patients at primary diagnosis). We performed immunohistochemical staining for CD8 and PD-L1, and NGS using a commercially available sequencing panel (Illumina Cancer Hotspot Panel V2) that targets 50 cancer-associated genes. Immunohistochemically, CD8-positive TILs showed a high positive score in cSCC without metastasis; in these cases, cSCC occurred predominantly in sun-exposed areas, the tumor size was smaller, and the total gene variation numbers were notably low. The tumor depth, PD-L1 positivity, and gene variation number with or without tumor metastasis were not related, but the gene variation number tended to be higher in cSCCs arising in non-sun-exposed areas. Tumor metastasis was more common in cSCC arising in non-sun-exposed areas, which decreased the number of TILs or CD8-positive cells. From a genetic perspective, the total gene alterations were higher in cSCC with metastasis. Among them, ERBB4 and NPM1 are presumably involved in cSCC tumorigenesis; in addition, GNAQ, GNAS, JAK2, NRAS, IDH2, and CTNNB1 may be related to tumor metastasis. These results provide information on potential genes that can be targeted for cSCC therapy and on immune checkpoint inhibitors that may be used for cSCC therapy.

The Characteristics of Breast Cancer Patients and Survival Analysis in the Southeast of Iran: A Retrospective Cohort Study

Background: Breast cancer is the most common cancer in women, with different survival rates depending on the patients’ characteristics. Objectives: This study aimed to evaluate breast cancer patients’ characteristics and survival rates in the southeast of Iran. Methods: The recorded data of breast cancer patients treated were collected from 2004 to 2020 in the Radiation Oncology Department of Kerman University of Medical Sciences, Iran. Overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare OS based on various factors. Three modeling strategies were considered to examine the patients’ survival using multiple Cox regression models. Results: The study included 309 patients who met the inclusion criteria; 153 (49.5%) were under 51 years of age. Luminal A intrinsic subtype accounted for 18.8% of cancer patients. Five- and 10-year OS rates were 86% and 63%, respectively. Five- and 10-year disease-free survival (DFS) rates for nonmetastatic patients were 82% and 60%, respectively. Multiple Cox regression showed that the percentage of the involved dissected lymph nodes, group stage, T-stage, M-stage, locoregional recurrence, and luminal subtype were independent prognostic factors for survival. Conclusions: Based on the results, the percentage of breast cancer patients under 50 years old is higher in the southeast of Iran compared to Western countries. In addition, the prevalence of the luminal A subtype is lower than in other regions. The survival results were consistent with other studies.

Multiparameter diagnostic model based on 18F-FDG PET metabolic parameters and clinical variables can differentiate nonmetastatic gallbladder cancer and cholecystitis

ObjectiveTo evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis.Patients and methodsIn total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy.ResultsThe ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA.ConclusionsThe multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.

MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series

BackgroundCancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ.MethodsThis multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients’ data were retrospectively collected from the clinical charts of seven recruiting Italian centres.ResultsMRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed.ConclusionsThis is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ.

Tumor-associated macrophages mediate gastrointestinal stromal tumor cell metastasis through CXCL2/CXCR2.

Tumor-associated macrophages (TAMs) are linked with the progression and poor prognosis of multifarious solid tumors, but the regulatory mechanisms involved in gastrointestinal stromal tumors (GIST) remain indistinct. This study intended to delve into the job of TAM-derived chemokines in promoting metastasis in GIST microenvironment. Expression levels of M2-TAM markers and CXCL2 in primary and metastatic tissues of GIST were analyzed by bioinformatics methods, and we analyzed the correlation between CXCL2 and M2-TAM markers. Immunofluorescence was applied to assay CXCL2 and M2-TAM marker protein (CD68 and CD206) expression in tumor tissues. Serum CXCL2 concentration in metastatic and non-metastatic patients was assayed by ELISA. The differentiation of THP-1 cells was tested by flow cytometry. Cell function test was utilized to analyze the viability, invasion and migration of GIST cells. Western blot was used to examine the expression of epithelial-mesenchymal transition (EMT)-related proteins. The mouse liver metastasis model was established, and the effects of CXCL2 and EMT-related genes on metastasis were confirmed by hematoxylin-eosin staining and immunohistochemistry experiments. Bioinformatics analysis ascertained that M2-TAM marker proteins and chemokine CXCL2 were highly expressed in GIST metastatic tissues, and CXCL2 and TAM were co-located in tumor tissues. Results of in vitro cell function experiments displayed that CXCL2 secreted by M2-TAM promoted the invasion, migration and EMT of GIST tumor cells, and the anti-CXCL2 antibody could block the metastasis promoting effect of CXCL2. Additionally, the silencing of CXCR2 in GIST cells inhibited the metastasis promoting effect of CXCL2. Animal studies further confirmed that CXCL2 promoted liver metastasis of GIST in vivo. This study preliminarily revealed the mechanism of M2-TAM promoting tumor metastasis by secreting CXCL2 in GIST tumor microenvironment, and proffered theoretical reference for the development of immunotherapy strategies targeting M2-TAM.

Advanced lung cancer inflammation index predicts the outcomes of patients with non-metastatic gastric cancer after radical surgical resection.

The prognostic value of the advanced lung cancer inflammation index (ALI) has been demonstrated in various tumors. However, the prognostic significance of ALI in non-metastatic gastric cancer (GC) remains unclear. This study aimed to identify the prognostic values of ALI in patients with non-metastatic GC who underwent radical surgical resection. Patients who underwent radical surgery for non-metastatic GC from January 2008 to September 2020 were enrolled in this study. The preoperative ALI was calculated as follows: body mass index × serum albumin/neutrophil to lymphocyte ratio. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression analyses were performed to assess the association between ALI and survival. The potential of ALI was supported by sensitivity testing based on the propensity score matching (PSM) analysis. Low preoperative ALI was significantly correlated with male gender (P=0.037), older age (P=0.004), T3/4 stage (P=0.001), lymph node metastasis (P=0.030), Tumor Node Metastasis (TNM) stage classification progression (P=0.004), and vessel invasion (P=0.001). Patients with low ALI showed worse OS (P<0.001) and CSS (P=0.001) compared to those with high ALI. Multivariable analysis showed that ALI was an independent prognostic factor for both OS [hazard ratio (HR) =1.55; 95% confidence interval (CI), 1.11-2.16]; P=0.010] and CSS (HR =1.46; 95% CI, 1.01-2.10; P=0.043) in non-metastatic GC patients who underwent radical surgical resection. Further PSM analysis confirmed the prognostic value of ALI in the PSM cohort. The preoperative ALI is associated with survival outcomes in patients who have undergone radical surgical resection for non-metastatic GC. Low ALI appears to predict a worse prognosis.

Cancer-specific mortality free survival rates in non-metastatic non-clear cell renal carcinoma patients at intermediate/high risk of recurrence

Cancer-specific mortality free survival rates in non-metastatic non-clear cell renal carcinoma patients at intermediate/high risk of recurrence