Non-metastatic Disease Research Articles

Initial Chemotherapy for Locally Advanced and Metastatic NUT Carcinoma

IntroductionNUT carcinoma (NC) is an underdiagnosed and aggressive poorly differentiated or squamous cell cancer. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown. Experts have recommended platinum- and ifosfamide-based therapy based on case reports. MethodsPatients with pathologically confirmed NC with known survival outcomes after chemotherapy and consented to participate in a worldwide registry were studied. Results were summarized using descriptive methods. ResultsThe study included 118 patients with NC. Median age was 34 (range: 1–82) years, 39% were women, and 61% harbored a BRD4::NUTM1 fusion. Patients received platinum (74%) or ifosfamide (26%, including regimens with both, 13%).Of 62 patients with nonmetastatic disease, 40% had a thoracic primary. Compared with platinum-based chemotherapy, patients who received ifosfamide-based chemotherapy had nominally higher progression-free survival (12 mo: 59% [95% CI: 32–87] versus 37% [95% CI: 22–52], hazard ratio = 0.68 [0.32, 1.42], p = 0.3) but not overall survival (OS). Among the 56 patients with metastatic disease, 80% had a thoracic primary. Ifosfamide had an objective response rate (ORR) of 75% (six of eight) and platinum had an ORR of 31% (11 of 36). Nevertheless, there was no difference in progression-free survival or OS.The 3-year OS of the entire cohort was 19% (95% CI: 10%–28%). Of the 11 patients alive greater than 3 years, all presented with nonmetastatic and operable or resectable disease. ConclusionThere is a numerically higher ORR for ifosfamide-based therapy compared with platinum-based therapy, with limited durability. OS at 3 years is only 19%, and development of effective therapies is an urgent unmet need for this patient population.

Characterization of an oligometastatic state in patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy.

Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC. Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine-based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18 months, and survival curves were estimated using the Kaplan-Meier method and compared between groups via the log-rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients. 121 patients were included with a median age of 62 years (37-86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n = 41) were alive at 12 months and 25% (n = 31) were alive at 18 months. Landmark analysis demonstrated a significant difference between patients surviving <18 months and ≥18 months regarding the presence of lung only metastases (36% vs. 16%, p = 0.04), number of organs with metastases (≥2 vs. 1, p = 0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p = 0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p = 0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p = 0.004), metastasis only in the liver (p = 0.04), and normalization of CA 19-9 (p < 0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19-9 (p = 0.03). In those patients that normalized their CA 19-9, median overall survival was 16 months. In this exploratory analysis normalization of CA-19-9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non-metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor-directed interventions.

DNA base oxidation in relation to TNM stages and chemotherapy treatment in colorectal cancer patients 2–9 months post-surgery

Accumulation of DNA damage is a critical feature of genomic instability, which is a hallmark of various cancers. The enzyme-modified comet assay is a recognized method to detect specific DNA lesions at the level of individual cells. In this cross-sectional investigation, we explore possible links between clinicopathological and treatment related factors, nutritional status, physical activity and function, and DNA damage in a cohort of colorectal cancer (CRC) patients with non-metastatic disease. Levels of DNA damage in peripheral mononuclear blood cells (PBMCs) assessed 2–9 months post-surgery, were compared across tumour stage (localized (stage I-II) vs. regional (stage III) disease), localization (colon vs. rectosigmoid/rectum cancer), and adjuvant chemotherapy usage, with the last dosage administrated 2–191 days prior to sampling. Associations between DNA damage and indicators of nutritional status, physical activity and function were also explored. In PBMCs, DNA base oxidation was higher in patients diagnosed with regional compared with localized tumours (P = 0.03), but no difference was seen for DNA strand breaks (P > 0.05). Number of days since last chemotherapy dosage was negatively associated with DNA base oxidation (P < 0.01), and patients recently receiving chemotherapy (<15 days before blood collection) had higher levels of DNA base oxidation than those not receiving chemotherapy (P = 0.03). In the chemotherapy group, higher fat mass (in kg and %) as well as lower physical activity were associated with greater DNA base oxidation (P < 0.05). In conclusion, DNA base oxidation measured with the enzyme-modified comet assay varies according to tumour and lifestyle related factors in CRC patients treated for non-metastatic disease.

Health-related quality of life among prostate cancer survivors with metastatic disease and non-metastatic disease and men without a cancer history in the USA.

Few studies have comprehensively compared health-related quality of life (HRQoL) between metastatic prostate cancer survivors, survivors with non-metastatic disease, and men without a cancer history. We used the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) data linkage to identify men aged ≥ 65 years enrolled in Medicare Advantage (MA) plans. Prostate cancer survivors were diagnosed between 1988 and 2017 and completed MHOS surveys between 1998 and 2019. We analyzed data from752 metastatic prostate cancer survivors (1040 survey records), 19,583 localized or regional prostate cancer survivors (non-metastatic; 30,121 survey records), and 784,305 men aged ≥ 65 years without a cancer history in the same SEER regions (1.15 million survey records). We used clustered linear regressions to compare HRQoL measures at the person-level using the Veterans RAND 12 Item Health Survey (VR-12) T-scores for general health and physical and mental component summaries. Compared to men without a cancer history, prostate cancer survivors were older, more likely to be married, and had higher socioeconomic status. Compared to men without a cancer history, metastatic prostate cancer survivors reported lower general health (T-score differences [95% confidence interval]: - 6.26, [- 7.14, - 5.38], p < .001), physical health (- 4.33, [- 5.18, - 3.48], p < .001), and mental health (- 2.64, [- 3.40, - 1.88], p < .001) component summaries. Results were similar for other VR-12 T-scores. In contrast, non-metastatic prostate cancer survivors reported similar VR-12 T-scores as men without a cancer history. Further analyses comparing metastatic and non-metastatic prostate cancer survivors support these findings. Interventions to improve health-related quality of life for men diagnosed with metastatic prostate cancer merit additional investigation. Interventions to improve health-related quality of life for metastatic prostate cancer survivors merit additionalinvestigation.

Patient management after primary rectal cancer diagnosis. Special focus on surgical treatment for non-metastatic disease

Background: Rectal cancer is a public health priority. Primary objectives of this study were to evaluate the quality of care for non-metastatic rectal cancer using process and outcome indicators. Delay of management, length of stay and readmission rate, sphincter preservation, morbidity, number of examined lymph nodes, mortality, overall and disease-free survivals were evaluated. Secondary objectives were to estimate the relationship between possible predictive parameters for (1) anastomotic leakage (logistic regression), (2) overall or disease-free survivals (cox regression). Methods: We performed a retrospective study on 312 consecutive patients diagnosed with primary rectal cancer between 2016 and 2019. We focused on the 163 patients treated by surgery for non-metastatic cancer. Results: The treatment began within 33 days (range 0–264) after incidence, resection rate was 67%. Digestive continuity rate in lower, middle and upper rectum was 30%, 87% and 96%. Median of 14 lymph nodes (range 1–46) was analyzed. Length of stay and readmission rate were 11 days (range 3-56) and 4%, respectively. Within 90 postoperative days, clinical anastomotic leakage occurred in 9.2% of cases, major morbidity rate was 17%, mortality 1.2%. Multivariate analysis revealed that stoma decreased the risk of anastomotic leakage [hazard ratio: 0.16; 95% confidence intervals: 0.04–0.63; p = 0.008]. The 5-year overall survival after surgery was 85 ± 4%, disease-free survival 83 ± 4%. Patients with major complications, male gender and R1/R2 resection margin had a poorer prognosis. Conclusion: This work showed encouraging results in rectal cancer treatment in our institution, our results were in line with recommendations at the time.

Experiences of patients with metastatic breast cancer: A qualitative study.

346 Background: More than 150,000 women live with incurable metastatic breast cancer (MBC) in the U.S. today. Survival for patients with MBC has greatly improved over recent decades, but studies exploring aspects of breast cancer survivorship (quality of life, health outcomes, coping, etc.) disproportionately focus on patients with non-metastatic disease. In an effort to better serve patients with MBC at our large tertiary cancer center, we launched a project to understand the preferences, perceived barriers, and unmet needs of this unique population. Methods: We employed focus groups to qualitatively examine patients living with metastatic breast cancer at all points in their journey with advanced cancer. Two experienced patient advocates provided feedback on the protocol. We invited 37 patients with metastatic breast cancer to participate in focus groups of 2-4 subjects. A researcher moderated these recorded conversations, asking subjects to discuss their memories of being diagnosed with MBC, their everyday experience of living with MBC, and their hopes and fears as they look forward. Written transcripts of the studies are coded using the Atlas.ti qualitative research software with intercoder reliability calculated among three coders. Recurrent themes are identified and described. Results: 32 patients participated in 13 focus groups. The majority of patients were white (88%), with an average age of 59 (median 61). Median time since diagnosis with metastatic disease was 57 months (4.75 years). 84% of patients had estrogen-receptor positive MBC, 28% had HER2-positive MBC, and none had triple negative disease. Initial themes identified include a desire for more information about treatments (new drugs, clinical trials, symptom management), and about planning in the face of uncertainty (especially financial, but also regarding end-of-life challenges, relationship changes). Patients also commonly expressed a need for more connection to fellow patients who can provide guidance and support. Analysis of data and formulation of findings are still ongoing, and will be completed by the end of 2023. Publication is planned for early 2024. Conclusions: Metastatic breast cancer cancer survivors continue to have unmet physical, practical, emotional, and spiritual needs. These needs change throughout a patient’s journey. The knowledge gained from exploring these needs will inform projects and management changes designed to better serve our patients by adapting existing services and creating new ones.

Conditional Overall Survival After Diagnosis of Non-Metastatic Colon Cancer: Impact of Laterality, MSI, and KRAS Status.

The prognostic relevance of laterality, microsatellite instability (MSI), and KRAS status in colon cancer has been established. However, their effect on conditional overall survival (COS) remains unknown. COS is the probability of surviving additional years after a time from diagnosis. The National Cancer Database (2010-2017) was queried for adults with non-metastatic colon cancer and known mutation status undergoing curative resection. COS was investigated at 2 years. Of 4838 patients, 3716 survived at least 2 years: 15% had stage I, 38% stage II, and 46% stage III disease. Fifty-nine percent had a right-sided tumor, 16% were MSI-high, and 37% were mutated KRAS (mKRAS). The proportion of patients alive at 2 years was higher for stage I compared with stage II and III (65 vs. 61 vs. 54%). The 5-year overall survival for stage I-III was 80, 76, and 67% for the initial cohort, and 90, 88, and 86% for those alive at 2 years. After adjustment, higher pathologic T and N stage, tumor deposits, and no chemotherapy were associated with worse COS (p < 0.01). While laterality and MSI status were not associated with COS, mKRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12-1.62). Patients with mKRAS had worse COS, suggesting that these mutations confer an aggressive biologic behavior, with patients remaining at higher risk of death 2 years after diagnosis. Routine evaluation of KRAS status should be considered in patients with non-metastatic disease for prognostication and to identify those who might benefit from modified surveillance protocols.

Relationship Between Metabolic Activity, Cellularity, Histopathological Features of Primary Tumors and Distant Metastatic Potential in Breast Cancer.

The aim of this study was to evaluate the relationship between the types of distant metastatic spread, histopathological features, and imaging features of primary tumor on positron emission tomography/magnetic resonance imaging (PET/MRI) for primary staging in newly diagnosed breast invasive ductal carcinoma (IDC) patients. Data from 289 female patients were retrospectively evaluated. Maximum standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and minimum apparent diffusion coefficient (ADCmin) values of primary tumors were obtained from PET/MRI. The patients were grouped as non-metastatic, oligometastatic (1-5 metastatic lesions) and multimetastatic (>5 metastatic lesions) disease according to the number of distant metastases, and divided into two groups as isolated bone metastasis (IBM) and mixed/soft tissue metastasis (M-SM) groups according to the sites of metastatic spread. Metabolic parameters had higher values and ADCmin had lower values in the multimetastatic and oligometastatic groups than in the non-metastatic group. MTV was the only parameter that showed significant difference between the multimetastatic and oligometastatic groups. MTV and TLG were significantly higher in the M-SM group than in the IBM group. 18F-fluorodeoxyglucose PET parameters had significantly higher values in grade 3, hormone receptor negative, human epidermal growth factor receptor 2 positive, triple negative, and highly proliferative (Ki-67 ≥14%) tumors. The prediction models that included imaging parameters to predict the presence of distant metastasis had higher discriminatory powers than the prediction models that included only histopathological parameters. Primary tumors with higher metabolic-glycolytic activity and higher cellularity were more aggressive and had higher metastatic potential in breast IDC. Compared with histopathological parameters alone, the combination of imaging parameters and histopathological features of primary tumors may help to better understand tumor biology and behavior.

Association Between Smoking Status and Opioid Dose in Prescriptions Written for Breast Cancer-related Pain

BACKGROUND: Cancer-related pain has historically been undertreated. Prescription opioids have been shown to be an integral part of the treatment of cancer pain. Despite the significant amount of scientific evidence that smoking is associated with variation in pain expression and opioid misuse in both cancer and non-cancer populations, little is known about the association between smoking status and opioid utilization in cancer populations. OBJECTIVES: To assess the association between smoking status and high-risk opioid-prescribing behaviors of oncologists prescribing opioids in the outpatient setting to patients with breast cancer-related pain. STUDY DESIGN: A retrospective cross-sectional study of opioid prescriptions written by oncologists for breast cancer-related pain was conducted using the Patient Cohort Explorer (PCE) database at the University of Mississippi Medical Center (UMMC) from March 15, 2015 to March 15, 2017. SETTING: Tertiary academic medical center. METHODS: De-identified data from UMMC PCE were utilized for this study. Patient-level information, such as age, gender, race, insurance status, and smoking status, were also selected for each prescription. Prescription-level data, such as name of opioid, dose, frequency, route, and primary diagnosis, were also obtained. Prescriptions were included if they are written in the outpatient setting, for breast cancer-related pain, and for women 18 years or older. Prescriptions were excluded if they were written by a specialist other than a medical oncologist or if the information necessary to calculate morphine milligram equivalence (MME) was missing. RESULTS: The sample consisted of 577 opioid prescriptions that were written in the outpatient setting to women ages 18 years and older for breast cancer-related pain. The majority of the sample were ages 46 to 64 years (60.5%), Nonwhite (75.2%), publicly insured (66.2%), and with nonmetastatic disease (86.1%). Almost one-fifth (19.6%) of the prescriptions were written to current smokers, 21.3% to former smokers, and 58.1% to nonsmokers. Nonsmoking status predicted an increased odds of receiving a prescription &gt;= 50 MME (odds ratio [OR] = 1.98, 95% confidence interval [CI]: 1.08-3.60, P = 0.030) and &gt;= 90 MME (OR = 6.29, 95% CI: 1.38-28.58, P = 0.017) compared to current smokers. Nonsmoking status also predicted an increased odds of receiving a prescription &gt;= 90 MME (OR = 4.29, 95% CI: 1.43-12.92, P = 0.009) compared to former smokers. LIMITATIONS: This cross-sectional sample was drawn from a single institution and only included the breast cancer population and may not be generalizable to other populations or institutions. Second, our sample was drawn from secondary data not collected for the purposes of our study. This limits the inclusion of other variables that may impact the opioid-prescribing behaviors of oncologists, potentially resulting in bias. CONCLUSIONS: During a time of heightened awareness of opioid-related harm, as well as implementation of national opioid-prescribing guidelines, current smoking may potentially be impacting how oncologists evaluate the need for opioids to treat breast cancer-related pain. Further studies that examine the relationship between smoking status, perceived need for opioids, and evaluative need for opioids in cancer populations are warranted. KEY WORDS: Cancer pain, opioids, smoking, breast cancer, opioid-prescribing guidelines, health policy, oncology, end of life

Defining the Oligometastatic State and Predicting Overall Survival in Uterine Cancers using a Recursive Partitioning Analysis: A National Cancer Database Analysis

Oligometastatic disease is an intermediate state between locoregional disease and widely metastatic disease. Studies have shown an overall survival advantage in oligometastatic patients treated aggressively in multiple cancers. However, few studies have explored this relationship in oligometastatic gynecological cancers. In this study, we sought to identify if an oligometastatic state with improved overall survival exists in uterine cancer and whether treatment patterns, or patient factors play a role in survival. The National Cancer Database was retrospectively analyzed in patients diagnosed with uterine cancer between 2004-2019. We excluded patients with non-metastatic disease at diagnosis, lack of metastatic sites listed, multiple primaries and missing survival data. Survival analyses were performed using Cox proportional hazards analyses and the Kaplan-Meier method and differences between groups were evaluated with log-rank tests. Recursive partitioning analysis (RPA) was performed using the rpart package in R. Amongst 641,276 women with uterine cancer, 17,343 were ultimately in our study population after exclusion who had a median age of 64 (range 18-90), median overall survival of 11.1 months, and a total of 24,337 metastases that represented the following metastatic sites: lung (35%), other (24%) (sites "other" than bone, brain liver or lung), liver (15%), bone (12%), distant lymph nodes (10%), brain (3%) and carcinomatosis (1%). Multivariate cox proportional hazards analysis identified the following variables as significantly associated with survival, which were then used for RPA: one metastatic site, treatment, grade, age, race, Charlson-Deyo score. The data was split 70/30% for training and validation, respectively. A survival model was built using RPA on the training data with 10-fold cross-validation and had accuracy of 76.25% (p = 3.393e-0.5). Survival prediction was performed on the internal validation data set with 76.69% accuracy (p = 0.004). RPA stratified 4 groups with the following median survivals: 5.9, 8.6, 29.5, and 43.8 months (log-rank test p<0.0001). The group with the best overall survival was defined by 1 metastatic site (carcinomatosis, distant lymph nodes and "other"), combination treatment with systemic therapy and radiation or surgery and low-grade histology. An oligometastatic state with involvement of one metastatic site does exist with improved survival in uterine cancer. The RPA defined groups may aid in identifying patients that are best suited for aggressive definitive combination therapy versus those that would be better suited for comfort care. Analysis is ongoing and will further delineate the relationship between specific treatment modalities and overall survival in patients with one metastatic site. This study may set the foundation for a prospective clinical trial.

An engineered niche delineates metastatic potential of breast cancer.

Metastatic breast cancer is often not diagnosed until secondary tumors have become macroscopically visible and millions of tumor cells have invaded distant tissues. Yet, metastasis is initiated by a cascade of events leading to formation of the pre-metastatic niche, which can precede tumor formation by a matter of years. We aimed to distinguish the potential for metastatic disease from nonmetastatic disease at early times in triple-negative breast cancer using sister cell lines 4T1 (metastatic), 4T07 (invasive, nonmetastatic), and 67NR (nonmetastatic). We used a porous, polycaprolactone scaffold, that serves as an engineered metastatic niche, to identify metastatic disease through the characteristics of the microenvironment. Analysis of the immune cell composition at the scaffold was able to distinguish noninvasive 67NR tumor-bearing mice from 4T07 and 4T1 tumor-bearing mice but could not delineate metastatic potential between the two invasive cell lines. Gene expression in the scaffolds correlated with the up-regulation of cancer hallmarks (e.g., angiogenesis, hypoxia) in the 4T1 mice relative to 4T07 mice. We developed a 9-gene signature (Dhx9, Dusp12, Fth1, Ifitm1, Ndufs1, Pja2, Slc1a3, Soga1, Spon2) that successfully distinguished 4T1 disease from 67NR or 4T07 disease throughout metastatic progression. Furthermore, this signature proved highly effective at distinguishing diseased lungs in publicly available datasets of mouse models of metastatic breast cancer and in human models of lung cancer. The early and accurate detection of metastatic disease that could lead to early treatment has the potential to improve patient outcomes and quality of life.

Initial Results of a Phase II Trial of Hypofractionated Radiation Therapy for Inoperable Soft Tissue Sarcoma

For patients with soft tissue sarcoma (STS) who cannot or choose not to have surgery, radiation can provide local tumor control in both palliative and definitive settings. Conventionally fractionated radiation provides modest (< 50%) rates of local control (LC) for STS at 2 years. To our knowledge, no prospective studies to date have evaluated the safety and efficacy of dose-escalated hypofractionated radiation therapy as treatment of inoperable STS. We hypothesized that dose-escalated, hypofractionated radiation therapy (RT) for inoperable STS could achieve higher rates of LC than reported in trials of conventionally fractionated RT. An IRB-approved single institution prospective phase II clinical trial of dose-escalated, hypofractionated RT as local control for STS was designed and completed planned accrual. Exclusion criteria included anti-cancer systemic therapy within the preceding two weeks. Patients underwent hypofractionated RT utilizing either CT-guided radiation (24, 50%) or MRI-guided radiation treatments (24, 50%). Data on patient characteristics, RT dose and fractionation, LC, toxicity, and overall survival (OS) was collected. The primary endpoint was local tumor control (stable, partial, or complete response according to RECIST) at 2-years after completion of radiation. Secondary endpoints were acute and late toxicity, rates of complete response, 5-year local tumor control, and progression-free and overall survival. Acute toxicity was graded on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale during treatment and at 3 months following RT. Forty-eight patients were enrolled, 17 with non-metastatic localized disease and 31 with metastatic disease. Median patient age was 64. Twenty-five men and 23 women were treated. Ninety-six total lesions were treated (36 lung, 7 extremity, 37 abdominopelvic, 16 other). Radiation dose per fraction ranged from 6-12 Gy for a total of 1-12 fractions (median dose was 52.5 Gy in 6 fractions. Median patient follow-up is 8.6 months (range 1 - 36 months). Six patients (13%) did not complete initial 3-month follow-up imaging. Of the 40 patients who have undergone 3-month follow up imaging, 32 (80%) had stable disease, 5 (12.5%) had partial response, 0 had complete response, and 3 (7.5%) had disease progression. Median PFS was 17.2 months at time of last follow up. Median OS was 12.9 months at time of last follow up. Twenty-five patients (52%) experienced an acute toxicity likely or possibly related to radiation. Three (6%) patients experienced CTACE grade 3 or greater treatment-related toxicity (pain, weakness, decreased range of motion, dermatitis). In this initial report of a prospective, single-institution clinical trial of hypofractionated RT for STS not undergoing resection, we report low rates of acute grade 3 or greater toxicity and high rates of tumor response. We will continue to follow these patients to assess late toxicity and durability of tumor control.

Impact of BCL-2 Expression on Course of Disease in Neuroblastoma.

The antiapoptotic BCL-2 protein has implications for maturation and differentiation of neural tissue and acts as a strong modulator of carcinogenesis in different tumors. Recent research focuses not only on its benefit as a prognostic factor, but also as a potential therapeutic target. The role of BCL-2 in neuroblastoma, the most common extracranial solid tumor in childhood, remains controversial. The aim of our study was to determine the gene expression level of BCL-2 in a large cohort of neuroblastoma patients and its correlation with clinical parameters. Tumor samples and clinical data were collected from 100 neuroblastoma patients treated according to the NB2004 protocol of the German Society of Pediatric Oncology and Hematology. BCL-2 gene expression levels were measured by quantitative reverse transcription polymerase chain reaction and correlated with clinical parameters. BCL-2 expression was detected in all tumor samples. Relative BCL-2 expression levels were higher in females versus males (1.839 vs. 1.342; p = 0.0143), in patients with low versus high International Neuroblastoma Staging System stage (2.051 vs. 1.463; p = 0.0206), in nonmetastatic versus metastatic disease (1.801 vs. 1.342; p = 0.0242), as well as in patients without presurgical chemotherapy (2.145 vs. 1.402; p = 0.0016), but was not associated with overall survival and MYCN amplification. Our study demonstrates the ubiquitous expression of BCL-2 in neuroblastoma and suggests the possibility for targeted therapy with BCL-2 inhibitors, even in lower-stage neuroblastoma. It also underlines the need for further research on concomitant genetic alterations for a better understanding of the impact of BCL-2 on this pediatric tumor type.

Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study.

The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.

176. NON-REGIONAL LYMPHADENOPATHY IN PATIENTS WITH ESOPHAGEAL CANCER TREATED WITH CURATIVE INTENT: A PROPENSITY MATCHED ANALYSIS OF PATHOLOGICAL AND SURVIVAL OUTCOMES

Abstract Background The management of patients with esophageal cancer and concurrent retroperitoneal or supraclavicular lymphadenopathy is controversial. Whilst these patients could be considered non-resectable, the survival benefit of neoadjuvant treatment followed by en bloc resection is not well described. The aim of this study was to explore the perioperative, pathological and survival outcomes of patients with esophageal cancer who presented with oligometastatic non-regional lymphadenopathy treated with neoadjuvant therapy and subsequent en bloc transthoracic esophagogastrectomy. Methods Between 01/2010 and 12/2022, a single center retrospective review of a prospectively maintained comprehensive esophageal cancer surgical database was performed. All patients with esophageal and junctional cancer with clinical non-regional (supraclavicular and retroperitoneal) lymphadenopathy were identified (Tany, Nany, M+). Only patients treated with neoadjuvant chemotherapy/chemoradiotherapy (nCT/nCRT) and extended en bloc transthoracic esophagogastrectomy including resection of the non-regional lymph node basin were included. Patients with gastric cancer and solid organ metastases were excluded. Propensity score matching was used to create a control group of clinically M- patients from same database to compare survival outcomes. Results Of the 46/1235 patients with non-regional lymphadenopathy, 39 met the inclusion criteria. Most had adenocarcinoma (35/39,89.7%) with retroperitoneal and supraclavicular lymphadenopathy in 26/39 (66.7%) and 16/39 (41.0%). nCRT and nCT was used in 5 and 34 patients respectively. Twenty-four received taxane based regimens and 24/39 (61.5%) adjuvant therapy. A trend towards improved overall survival was noted when comparing the study and control groups (27.0 vs 17.0 months, p = 0.065). However, cM+(retroperitoneal) had similar survival to the control group with both being higher than cM+(supraclavicular) (27.0 vs 21.0 vs 13.0 months, p = 0.039). Non-regional nodal basin sterilization occurred in 20/36 (55.6%) and was not associated with improved survival. Conclusion Whilst non-regional lymph node disease in the setting of esophageal cancer can be treated with neoadjuvant therapy and curative en bloc extended transthoracic resection, it seems that in terms of survival patients with retroperitoneal disease benefit the most. In this group of patients, equivalent survival to those with non-metastatic disease is achievable. Further understanding into those who would benefit from such a regimen is urgently needed.

Impact of Age, Race, and Gender on the Association Between Marital Status and Treatment Outcomes in Oral Tongue Squamous Cell Carcinomas.

Background: The objective of this study is to assess whether the impact of marital status on oral tongue squamous cell carcinomas (OTSCC) prognosis varied by gender, age, and race. Methods: We examined the clinicopathological variables using chi-squared tests, and we evaluated the association between survival and different variables using the methods of Kaplan-Meier. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. Results: A total of 5282 patients were analyzed. The rate of being married was higher among Asian or Caucasian, and this rate decreased with higher tumor stage. While both married male and female survivors benefit from their marital status, we found a differential in OS based on gender, with females benefiting more than males (male P = .038; female P = .009, respectively). Patients who were divorced/separated/widowed (male HR = 1.275, 95% CI: 1.085-1.499; female HR = 1.313, 95% CI: 1.083-1.593) and never married (male HR = 1.164, 95% CI: 0.983-1.378; female HR = 1.224, 95% CI: 0.958-1.565) had increased hazard of OS compared with married/partnered patients (male P = .038; female P = .009). Subgroups analysis shows that the effect of marital status was significantly associated with treatment outcome only in Caucasian patients aged 50 years or older who harbored non-metastatic disease and received surgery (P < .001). Conclusion: While there are survival benefits for married patients with OTSCC, married/partnered females may benefit more than males. Age, race, and gender could affect the correlation between marital status and survival.

Incidence, Stage, Treatment, and Survival of Noncardia Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide, and investigating its incidence, characteristics, treatment, and outcomes over the past decades can help in selecting clinical strategies and future research directions. To analyze the trends in incidence, staging, and treatment of gastric cancer. This nationwide, population-based cohort study included patients diagnosed with noncardia gastric cancer (NCGC) between 1989 and 2021 in the Netherlands. Differences in tumor characteristics, treatment, and survival were analyzed per fixed time periods (1989-1993, 1994-1998, 1999-2003, 2004-2008, 2009-2013, 2014-2018, and 2019-2021). In total, 47 014 patients (median [IQR] age, 73 [64-80] years; 28 032 [60%] male patients) were identified with mostly adenocarcinomas of the antrum region (when location was known). Age-standardized incidence decreased from 20.3 to 6.1 per 100 000 person-years between 1989 and 2021. During the study period, unknown T and N stages were recorded less frequently, and metastatic disease was diagnosed more frequently (1989-1993: 2633 of 9493 patients [28%]; 2019-2021: 1503 of 3200 patients [47%] in 2019-2021). Over time, fewer patients with metastatic disease underwent surgery with or without other treatment modalities (68% in 1989-1993 vs 64% in 2019-2021), and palliative chemotherapy in metastatic NCGC increased from 9% to 40%. For patients with nonmetastatic disease, 5-year relative survival improved from 28% (95% CI, 26.5%-29.2%) to 36% (95% CI, 33.5%-37.6%) between 1989 and 2021. For patients with nonmetastatic disease undergoing a resection, 5-year survival increased from 40% (95% CI, 38.3%-41.8%) to 51% (95% CI, 47.9%-53.3%). For patients with metastatic disease, 1-year relative survival increased from 10% (95% CI, 8.7%-11.1%) to 19% (95% CI, 17.2%-21.6%), but 3-year relative survival remained poor at 5% (95% CI, 3.6%-7.5%). In this nationwide cohort study involving 47 014 patients diagnosed with NCGC (1989-2021), the results showed a decrease in incidence, more accurate staging, a shift in treatment modalities, and improved patient survival.

Peripheral Blood CD8+ T-Lymphocyte Subsets Are Associated with Prognosis in Prostate Cancer Patients

Background: Various studies have reported associations between frequencies of total peripheral blood lymphocytes and prostate cancer prognosis, but none so far has addressed the prognostic role of CD8+ T-lymphocyte subsets. Methods: A total of 43 prostate cancer patients with metastatic disease and 81 patients with non-metastatic disease were included in this study. Flow cytometry analyses were employed for determining the frequencies of peripheral CD8+ T-lymphocyte subsets. Results: Statistically significant lower levels of terminally differentiated effector (TEMRA) cells in patients with non-metastatic disease vs. patients with metastatic disease were observed. Central memory (CM) and effector memory (EM) CD8+ subsets, were found to be significantly higher in patients with non-metastatic disease vs. patients with metastatic disease. A similar profile was revealed when these CD8+ subsets were analyzed based on the patients’ Gleason scores, as well as by combined disease stage (i.e., non-metastatic vs. metastatic disease) and Gleason score. Conclusions: Peripheral blood-derived CD8+ T-lymphocyte memory subsets could function as biomarkers for the prognosis of PCa.

Apport de l’IRM corps entier au bilan initial du liposarcome myxoïde

IntroductionMyxoid liposarcoma is a soft tissue sarcoma associated with multifocal metastases at diagnosis. These metastases are asymptomatic and occult on CT and FDG-PET and can alter the therapeutic management and prognosis. In this context, we evaluated the contribution of whole-body MRI to the initial workup of patients with myxoid liposarcoma. MethodThis retrospective study was conducted between January 2015 and December 2020 at the Oscar Lambret Center. We enrolled 22 patients who were diagnosed with myxoid liposarcoma and underwent whole-body MRI at diagnosis. The number of metastases at diagnosis, their location, and the visibility of these lesions on CT were evaluated. Associations between clinical features, presence of metastasis, and their impact on management were assessed. ResultsSixteen patients (72.7%) had non-metastatic disease at the initial diagnosis, and 15 of these patients were managed using local treatment. Six patients (27.3%) had metastases at multiple locations and received chemotherapy. The main locations were the bones (n=5) and lungs (n=3). In five patients with metastases, whole-body MRI demonstrated additional lesions that were not visible on CT (bone and soft tissue lesions). Only the presence of a round cell contingent (P=0.009) was found as a criterion associated with the presence of metastases. ConclusionThe patients’ young age, absence of reliable prognostic factors at diagnosis, asymptomatic nature of the lesions, and the benefits of early and targeted therapeutic management encourage the use of whole-body MRI as part of the initial work-up as it seems to provide a better initial staging compared with conventional imaging.

Elevated Tumor Cell-Intrinsic STING Expression in Advanced Laryngeal Cancer

Laryngeal cancer is the second most common malignancy of the head and neck, worldwide. Immunotherapy targeting checkpoint inhibitors has been approved for the treatment of patients with recurrent or metastatic laryngeal cancer but has a relatively low response rate and outcomes that leave many patients underserved. Targeting the cGAS–STING signaling pathway can potentially improve the activation of immune effector cells, although its role in the development and progression of laryngeal cancer has not yet been investigated in depth. Fifty-nine tumor samples from patients with pathologically confirmed squamous cell carcinoma of the larynx, stage I–IV non-metastatic disease, who were treated at the University Hospital of Split, were immunohistochemically stained for the expression of STING, cGAS, CD8, CD68, and CD163. Elevated tumor cell-intrinsic STING expression was positively associated with stage IV (p = 0.0031), pT3, and pT4 laryngeal cancers (p = 0.0336) as well as with higher histological grades (G2 and G3) (p = 0.0204) and lymph node-positive tumors (p = 0.0371). After adjusting for age, sex, location, and cGAS expression, elevated STING expression was significantly associated with stage IV cancer in a multiple logistic regression model (β = 1.849, SE = ±0.8643, p = 0.0324). Elevated STING expression represents a potentially favorable predictive biomarker for new therapeutic approaches involving STING agonists combined with immunotherapy and DNA-damaging agents (radiotherapy, cisplatin, and PARP inhibitors) in laryngeal cancer.