Non-metastatic Cancer Research Articles

Expression of Heat Shock Protein 90 in Testicular Cancer: A Retrospective Cohort Study.

The HSP90 marker is believed to play a constructive role in facilitating neoplastic transformation mainly via interaction with multiple pro-survival proteins. Welldesigned studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors. The current study aimed to investigate the expression of HSP90 in various types of testicular cancer and highlight its expression in embryonal testicular cancer. Immunohistochemical staining for HSP90 in 84 male patients, with nonmetastatic testicular cancer, who underwent orchiectomy from 2000 to 2023, was retrospectively performed at the Laboratory Department of General Hospital of Nikaia in Greece. A total of 84 males, with a mean age of 36.2 years, who have undergone high-cord radical orchiectomy, were included in this study. Out of the included males, 28.57% had embryonal carcinoma, 23.81% had seminoma, 19.05% had yolk sac tumor, 11.9% had mature teratoma, 9.52% had immature teratoma, and 7.14% had choriocarcinoma. HSP90b was positive in all embryonal carcinoma, seminoma, and choriocarcinoma cases, while it was positive in 75% of the yolk sac tumor, 75% of mature teratoma, and 75% of immature teratoma specimens. HSP90 was found negative in all choriocarcinoma, mature teratoma, and immature teratoma specimens, while it was positive in 25% of yolk sac tumor, 8.33% of embryonal carcinoma, and 10% of seminoma cases. Concerning the expression of HSP90b, a statistically significant relationship was found between excised tumor specimens and normal parenchyma specimens, especially in sac cases (p <0.001). Regarding HSP90a expression, a statistically significant relationship (OR=21.5, p =0.021) was found between excised tumor specimens and normal parenchyma specimens, especially in embryonal carcinoma cases (p <0.001). HSP90b is highly expressed in the majority of the types of testicular tumors, both in tumor and normal parenchyma specimens, while HSP90a staining is negative in resected specimens. Further well-designed studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.

Local excision vs. proctectomy in patients with ypT0–1 rectal cancer following neoadjuvant therapy: a propensity score matched analysis of the National Cancer Database

BackgroundWe aimed to evaluate outcomes of organ preservation by local excision (LE) compared to proctectomy following neoadjuvant therapy for rectal cancer.MethodsThis retrospective observational study using the National Cancer Database (NCDB) included patients with locally advanced non-metastatic rectal cancer (ypT0–1 tumors) treated with neoadjuvant therapy between 2004 and 2019. Outcomes of patients who underwent LE or proctectomy were compared. 1:1 propensity score matching including patient demographics, clinical and therapeutic factors was used to minimize selection bias. Main outcome was overall survival (OS).Results11,256 of 318,548 patients were included, 526 (4.6%) of whom underwent LE. After matching, mean 5-year OS was similar between the groups (54.1 vs. 54.2 months; p = 0.881). Positive resection margins (1.2% vs. 0.6%; p = 0.45), pathologic T stage (p = 0.07), 30-day mortality (0.6% vs. 0.6%; p = 1), and 90-day mortality (1.5% vs. 1.2%; p = 0.75) were comparable between the groups. Length of stay (1 vs. 6 days; p < 0.001) and 30-day readmission rate (5.3% vs. 10.3%; p = 0.02) were lower in LE patients. Multivariate analysis of predictors of OS demonstrated male sex (HR 1.38, 95% CI 1.08–1.77; p = 0.009), higher Charlson score (HR 1.52, 95% CI 1.29–1.79; p < 0.001), poorly differentiated carcinoma (HR 1.61, 95% CI 1.08–2.39; p = 0.02), mucinous carcinoma (HR 3.53, 95% CI 1.72–7.24; p < 0.001), and pathological T1 (HR 1.45, 95% CI 1.14–1.84; p = 0.002) were independent predictors of increased mortality. LE did not correlate with worse OS (HR 0.91, 95% CI 0.42–1.97; p = 0.82).ConclusionOur findings show no overall significant survival difference between LE and total mesorectal excision, including ypT1 tumors. Moreover, patients with poorly differentiated or mucinous adenocarcinomas generally had poorer outcomes, regardless of surgical method.

Excess Body Weight and the Risk of Second Primary Cancers Among Cancer Survivors

Little is known about the causes of second primary cancers among individuals with a history of cancer. Descriptive studies have suggested that lifestyle factors, including excess body weight, may be important. To investigate whether excess body weight is associated with the risk of a second primary malignant neoplasm among cancer survivors. This cohort study of adults in 21 states in the US used data from the Cancer Prevention Study II Nutrition cohort, a large prospective study that invited participants to respond to a survey in 1992 and biennial surveys starting in 1997, and who were followed-up through 2017. Eligible participants included those who received a diagnosis of a first primary nonmetastatic invasive cancer between 1992 and 2015. Data analysis occurred from September 2023 to March 2024. Body mass index (BMI), computed from self-reported height and weight at the time of the first primary cancer diagnosis (mean [SD] years to diagnosis, 1.7 [1.5] years). Main outcomes included a second primary cancer or an obesity-related second cancer. Cancer diagnoses were reported on biennial surveys and verified through medical record abstraction or linkage with state cancer registries. This cohort included 26 894 participants who received a diagnosis of a first nonmetastatic primary cancer (mean [SD] age at first cancer diagnosis, 72.2 [6.5] years; 15 920 male [59.2%]). At the time of first diagnosis, 11 497 participants (42.8%) had overweight and 4684 (17.2%) had obesity. During a median (IQR) follow-up time of 7.9 (3.4-13.6) years, 3749 (13.9%) participants received a diagnosis of a second primary cancer, of which 1243 (33.2%) were obesity-related second primary cancers. Compared with cancer survivors whose BMI was in the normal range (18.5 to <25), there was 15% increased risk of any second primary cancer for those who had overweight (25 to <30; adjusted hazard ratio [aHR], 1.15; 95% CI, 1.07-1.25) and a 34% increased risk for those who had obesity (BMI ≥30; aHR, 1.34; 95% CI, 1.21-1.48), with greater risk for obesity-related second primary cancers, including a 40% increased risk for those with overweight (aHR, 1.40; 95% CI, 1.22,-1.61) and a 78% increased risk for those with obesity (aHR, 1.78; 95% CI, 1.51-2.11). In this cohort study of older survivors of nonmetastatic cancer, those who had overweight or obesity at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially an obesity-related second cancer. Given the high prevalence of overweight and obesity among cancer survivors, it is important to promote survivorship care guidelines recommending weight management and increase awareness of second cancers among physicians and cancer survivors.

Abstract A054: Collagen fiber architecture modulates PDAC cell and organoid phenotype

Abstract Introduction Collagen plays a significant role in the development of pancreatic ductal adenocarcinoma (PDAC). Disease progression is mediated by a dense collagenous stroma, which acts as a barrier to drug delivery and immune cell access. Current in vitro models do not well represent the collagenous stroma seen in PDAC. The aim of this study is to develop a fibrillar collagen-based hydrogel system which mimics the tumour microenvironment seen in PDAC and assess cell-mediated collagen remodeling. Methods Metastatic SUIT2-007 pancreatic cancer cells, non-metastatic BxPC3 pancreatic cancer cells, and human pancreatic stellate cells (hPSCs) were encapsulated in bovine type I collagen gels of various concentrations. KPC mouse derived tumour organoids were also encapsulated in bovine type I collagen gels of 2 mg/ml and 6 mg/ml concentrations, basement membrane extract (BME), and a combination of BME and collagen gel. Cell viability and proliferation was assessed using Live/Dead imaging and CellTitre-Glo 3D respectively. Cell mediated collagen remodeling was assessed via monitoring of gel contraction on the mm scale, and confocal reflectance microscopy on the cellular scale. Collagen contraction around cells was assessed by measuring the pixel intensity of collagen fibrils within the vicinity of the cell. Cell phenotype was assessed via immunofluorescent staining and qPCR. Results Collagen concentration alters the hydrogel structure and stiffness, with 3 mg/ml collagen resulting in straighter, shorter and thicker fibrils. Metastatic SUIT-007 cells contracted collagen gels more rapidly than non-metastatic BxPC3 cells, with both achieving similar contraction by day 7. SUIT2-007 cells remodel and align soft 1 mg/ml gels while 3 mg/ml gels proved to be sufficiently stiff to resist remodeling. Cellular collagen association was increased in more elongated SUIT-007 cells than in BxPC3 cells. Organoid proliferation varies with hydrogel collagen concentration. Conclusion Metastatic SUIT2-007 cells were able to remodel collagen more rapidly and to a greater extent than non-metastatic BxPC3 cells. Collagen supports an invasive organoid phenotype. Collagen gels combined with confocal reflectance microscopy provide a platform for the quantitative assessment of cell-matrix interactions in PDAC. Acknowledgements This project was funded by a Medical Traineeship from UCD School of Medicine, and summer student scholarships from Irish Cancer Society and Breakthrough Cancer Research. We acknowledge the Conway Imaging Core Facility for assistance with microscopy. Citation Format: Ciara L Doyle, Shanu Xavier, Jarren Y.S Lu, Leah Fallon, Anwesha Sarkar, Jan J Baguyo, Maela Gars, Stephen D Thorpe. Collagen fiber architecture modulates PDAC cell and organoid phenotype [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A054.

Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial.

Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by a defective DNA mismatch repair system, resulting in hypermutated and highly immunogenic tumors. Although patients with dMMR CC have limited benefit from chemotherapy, these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses. Here, based on data from melanoma studies, we postulated a high efficacy and favorable toxicity profile of anti-PD-1 plus anti-LAG-3. In the NICHE-3 study, a total of 59 patients with locally advanced dMMR CC were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 57 of 59 (97%; 95% confidence interval (CI): 88-100%) patients, meeting the primary endpoint. Responses included 54 (92%; 95% CI: 81-97%) major pathologic responses (≤10% residual viable tumor) and 40 (68%; 95% CI: 54-79%) pathologic complete responses. With a median follow-up of 8 months (range, 2-19), one patient had recurrence of disease. The treatment displayed an acceptable safety profile, with all-grade and grade 3-4 immune-related adverse events (irAEs) occurring in 80% and 10% of patients, respectively. The most common irAEs were infusion-related reactions (29%), thyroid dysfunction (22%) and fatigue (20%). In conclusion, our results show that neoadjuvant nivolumab/relatlimab induces high rates of pathologic responses and that further investigation of this treatment in larger studies is warranted. These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140 .

Association of housing status and cancer diagnosis, care coordination and outcomes in a public hospital: a retrospective cohort study

ObjectivesCancer is a leading cause of death in unhoused adults. We sought to examine the association between housing status, stage at diagnosis and all-cause survival following cancer diagnosis at a...

Needs, preferences, and patient participation for a randomized controlled trial on postneoadjuvant complete tumor response: A qualitative study of patients with esophageal cancer

PurposeFor patients with clinical complete response of non-metastatic esophageal cancer (EC) after neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT), the two treatment options obligate postneoadjuvant surgery as the current standard treatment (surgery on principle) versus active surveillance with surgery as needed only in recurring loco-regional tumor as a possible future alternative or standard exist. Since these treatments are presumably equivalent in terms of overall survival, patient-centered information can encourage the discussion with the treating physician and can make it easier for patients to make trade-offs between the advantages and disadvantages of the treatment alternatives in a highly distressed situation.MethodsA qualitative prospective cross-sectional study was conducted to create patient-centered information material that is based on patients’ preferences, needs, and concerns regarding the two treatment options, and to investigate the potential participation in a consecutive randomized controlled trial (RCT). Therefore, EC patients (N = 11) were asked about their attitudes.ResultsConcerns about the surgery and possible postoperative impairments in quality of life were identified as most mentioned negative aspects of surgery on principle, and recurrence and progression fear and the concern that surgery cannot be avoided anyways as most named negative aspects of surgery as needed. In regard to the participation in an RCT, making a contribution to science and the hope that the novel therapy would be superior to the established one were relevant arguments to participate. On the other hand, the lack of a proactive selection of treatment was named an important barrier to participation in an RCT.ConclusionThe importance of adapting medical conversations to the patients’ lack of expertise and their exceptional cognitive and emotional situation is stressed. Results of this study can be used to improve patient-centered information and the recruitment of patients in RCTs in cancer.

Reasons for Surgical Attrition Among Nonmetastatic Upper Gastrointestinal Cancer Patients: A Single Institutional Experience.

Upper gastrointestinal (UGI) cancers require multidisciplinary treatment, but surgery provides the only potentially curative option. We sought to understand reasons for attrition before surgery within our regional hospital network. We performed chart reviews of patients (age 18-80) with stage I-III UGI cancers (gastroesophageal junction, gastric, and hepatopancreatobiliary adenocarcinomas) in our multihospital cancer registry from 2015 to 2021. Our primary outcome was reasons for surgical attrition. Univariable analysis identified factors related to surgical attrition and the Kaplan-Meier method estimated overall survival based on surgery receipt. Seven hundred and ninety-two patients were included in our analysis, of whom 107 (13.5%) did not undergo curative surgery. Reasons for not undergoing surgery included medical comorbidities (30.8%), patient preference/nonmedical barriers (24.3%, which included: not interested without further explanation, worried about complications, nonadherence to appointments, insurance issues, did not wish for blood transfusion, lack of social support, preferring home care, and worried about recurrence), psychosocial (5.6%), progression while on neoadjuvant therapy or waiting for transplant (15.0% and 7.5%), poor performance status (3.7%), side effects of neoadjuvant therapy (3.7%), and death unrelated to treatment or unknown cause (9.4%). Nonsurgical management was not associated with race, socioeconomic status, or distance traveled for care. Survival was greatly improved for patients who underwent surgery (158 vs. 63 weeks, p < 0.05). Nearly one in seven patients (18-80 years old) with UGI cancers evaluated at our academic cancer center did not undergo surgical resection. Reasons for surgical attrition included potentially modifiable issues, and addressing these barriers could help overcome inequities in cancer treatment and survival.

FP4.1 - Impact of adjuvant chemotherapy on the 5 Year Overall Survival for non-metastatic colon cancer patients in Bulgaria - a population wide based observational study

Abstract Aim Colon cancer patients who receive adjuvant chemotherapy later in life have lower survival rates. NCCN guidelines recommend the use of adjuvant chemotherapy for patients with non-metastatic colon cancer. Our study's objective was to examine how adjuvant chemotherapy affected the 5-year overall survival (OS) of patients diagnosed with non-metastatic colon cancer in Bulgaria. Methodology This is a retrospective population-wide observational analysis of 8968 cases that was reported as colorectal cancer (CRC) in the Bulgarian National Cancer Registry (BNCR) from 2015 to 2016. The mean and median ages of patients with right colon (RCC) and left colon (LCC) were examined. An analysis was conducted to determine the effect of adjuvant chemotherapy on the 5-year overall survival for non-metastatic colon cancer. To estimate the statistical significance, chi-squared tests, ANOVA, and the Kaplan-Meier curve with log rank were employed. Results In comparison to LCC, RCC had a higher mean age at diagnosis of 68.9 versus 67.41 (p-Value=&amp;lt;0.001). For RCC and LCC, the corresponding median ages at diagnosis were 69 and 68. The 5-year OS for patients with non-metastatic colon cancer who received adjuvant chemotherapy was higher than for patients who did not (67.8% vs. 59%, respectively, p-Value=0.007), according to our study. Adjuvant chemotherapy was given to slightly more than 30% of patients. Conclusion The 5-Year OS for patients with non-metastatic colon cancer is improved by adjuvant chemotherapy, and Bulgaria should follow NCCN guidelines. The implementation of a systematic screening program can be advantageous for Bulgaria as well.

Survival after surgery beyond total mesorectal excision for primary locally advanced rectal cancer, a population-based study

BackgroundThe aim of this study was to compare relative survival in non-metastatic rectal cancer clinically staged as T3-T4 requiring beyond total mesorectal excision (TME) to that after standard TME. MethodsThis population-based study included all patients operated with anterior resection, abdominoperineal excision or Hartmann's procedure for non-metastatic rectal cancer clinically staged as T3-T4 in Sweden between 2009 and 2018. Relative survival was analysed in relation to surgery beyond TME (bTME), which was subcategorized as bTME- and bTME + to account for extent of resection. In all survival analyses, follow-up started at 90 days after surgery. Based on a causal model defined a priori excess mortality rate ratios (EMRR) were estimated using Poisson regression. ResultsOf 8272 included patients 1220 (14.7 %) were operated bTME. In a model adjusted for age and sex bTME was associated with higher excess mortality compared to standard TME (EMRR: 1.76, 95%CI:1.52–2.04). This association persisted after additional adjustment for tumour characteristics, neoadjuvant therapy and hospital volume (EMRR: 1.32, 95%CI:1.11–1.56) and was mainly attributable to restricted relative survival after bTME- (EMRR: 1.42, 95%CI:1.18–1.72) as EMRR after bTME+ was 1.07 (95%CI:0.80–1.44). ConclusionThis national population-based study showed inferior relative survival after bTME compared to standard TME in non-metastasized rectal cancer cT3-cT4. Unexpectedly this difference was mainly seen after bTME of limited extent.

Trends in Racial and Ethnic Differences in Declined Surgery for Resectable Malignancies in the United States.

To assess trends in patients' decisions to decline cancer surgery in the United States by race and ethnicity. Racial and ethnic differences in declining potentially curative cancer surgery are suggested to be due to systemic inequities in healthcare access and mistrust of healthcare systems, among other factors. Despite ongoing national efforts to address these inequities, it is unknown whether differences in rates of declined cancer surgery have improved. Using population-based data from the US Surveillance, Epidemiology, and End Results Program from 2000 to 2019, we studied individuals with non-metastatic cancer who were recommended surgery. Racial and ethnic differences in risk-adjusted rates of declined surgery were evaluated by year and cancer site using mixed-effects logistic regression. Of 2,740,129 patients with resectable, non-metastatic cancer, Black patients had the highest rates of declined surgery (2.10% [95% CI, 1.91-2.31%]) while White patients had the lowest (1.04% [95% CI, 0.95-1.14%]). From 2000 to 2019, racial and ethnic differences in declined surgery did not change significantly, except for a decrease in the difference between Hispanic and White patients (difference-in-difference, -0.4% [95% CI, -0.71% to -0.09%]). When stratified by cancer site, Black-White differences in rates of declined surgery decreased significantly (but were not eliminated) for four of fifteen sites (esophageal, pancreatic, lung, and kidney) ( P <0.001). Patients from racial and ethnic minority groups were more likely to decline surgical intervention for potentially curable malignancies and these differences have persisted over time. Further work is needed to understand the causes of these differences and identify opportunities for improvement.

Tumor-informed circulating tumor DNA in urothelial carcinoma: a promising novel biomarker.

Tumor-informed circulating tumor DNA (ctDNA) is an emerging biomarker in urothelial carcinoma. Recent clinical trials have investigated the integration of ctDNA into clinical decision-making in patients with muscle-invasive bladder cancer, their findings suggest that ctDNA may potentially revolutionize the way we stratify patients to different treatment modalities. ctDNA informed from TURBT specimens was found to be prognostic of disease outcomes among patients with localized nonmetastatic bladder cancer. Detectable precystectomy ctDNA status was associated with worse survival outcomes. Additionally, ctDNA status was predictive of adverse disease on radical cystectomy, including the likelihood of disease upstaging, lymph node involvement, and having a locally advanced disease (≥pT3a). In the postcystectomy minimal residual disease (MRD) period, ctDNA status may refine patient selection to adjuvant therapy, and if validated by ongoing clinical trials, patients with undetectable postcystectomy ctDNA status may forgo adjuvant treatment, regardless of pathological stage. On the contrary, patients with pre or postcystectomy detectable ctDNA status may benefit from treatment intensification. The integration of ctDNA in clinical decision-making has the potential to revolutionize the way we manage urothelial carcinoma by refining patient selection to different treatment modalities. This approach could ultimately lead to personalization of oncological care, with the potential to reduce both treatment-related and financial toxicity.

Geographic and racial disparities in the quality of surgical care among patients with nonmetastatic uterine cancer

BackgroundWhile utilization of minimally invasive surgery and sentinel lymph node biopsy have increased considerably over time for surgical management of early-stage uterine cancer, practice varies significantly in the United States, with disparities among low-volume centers and patients of Black race. A significant number of counties in the US are without a gynecologic oncologist, and almost half of counties with the highest gynecologic cancer rates lack a local gynecologic oncologist. ObjectiveTo evaluate relationships of distance traveled and proximity to gynecologic oncologists with receipt of and racial disparities in the quality of surgical care in patients undergoing hysterectomy for nonmetastatic uterine cancer. Study designPatients who underwent hysterectomy for nonmetastatic uterine cancer in Kentucky, Maryland, Florida, and North Carolina were identified in 2012-2018 State Inpatient Database and State Ambulatory Surgery Services Database files. County-to-county distances were used for distances traveled and to nearest gynecologic oncologist. Factors associated with receipt of minimally invasive surgery and lymph node dissection were analyzed using multivariable logistic regression models including assessment for interactions of travel for surgery with patient race. ResultsAmong 21,837 cases, 45.5% lived in a county without a gynecologic oncologist; 55.5% overall traveled to another county for surgery, including 88% of those lacking a local gynecologic oncologist. Patients lacking local access to a gynecologic oncologist in their county who did not travel for surgery were more likely to receive open surgery and no lymph node dissection, and those in counties without access in any surrounding county were even more likely. Among patients in counties without a gynecologic oncologist, those who traveled for surgery had similar likelihood of minimally invasive surgery (71%) but greater likelihood of lymph node dissection (64.7% vs 57.2%) compared to non-travelers. Among counties without a gynecologic oncologist, longer distance traveled was associated with receipt of lymph node assessment. Compared to non-Black patients, Black patients were less likely to undergo minimally invasive surgery (57.0% vs 74.1%). In adjusted regression models controlling for a diagnosis of fibroids, Black race was an independent risk factor for receipt of open surgery. There was a significant interaction of Black race and travel for surgery, with Black patients who lived in counties without a gynecologic oncologist who did not travel facing incrementally lower likelihood of receiving minimally invasive surgery (OR=0.57 vs non-Black patients who traveled for surgery; OR=0.60 as interaction term; p<0.001 for both). Similar disparities in surgical quality by race were noted for Black patients who lived in counties with a gynecologic oncologist who traveled out of county for surgery. ConclusionsPatients, particularly those of Black race, who lack local access to gynecologic oncologist specialty care benefit from traveling to specialty centers to ensure access to high-quality surgery for nonmetastatic uterine cancer. Further work is needed to ensure equitable and universal access to high-quality care through patient travel or specialist outreach.

162 a Retrospective Review of Radiation Therapy in Non-Metastatic Muscle-Invasive Bladder Cancer at a Tertiary Care University Hospital in Pakistan

162 a Retrospective Review of Radiation Therapy in Non-Metastatic Muscle-Invasive Bladder Cancer at a Tertiary Care University Hospital in Pakistan

1961O Nivolumab plus chemoradiotherapy in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), not undergoing cystectomy: A phase II, randomized study by the Hellenic GU Cancer Group

1961O Nivolumab plus chemoradiotherapy in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), not undergoing cystectomy: A phase II, randomized study by the Hellenic GU Cancer Group

Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions.

Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TMEs). While the shortcomings of two-dimensional (2D) models in replicating in situ cell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiology in situ.

Mechanistic insights into behavioral clusters associated with cancer-related systemic inflammatory response.

This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions. GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster. GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications.

Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario.

The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB-IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)-IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.

Enhanced recovery and reduced conversion rates in robotic rectal cancer surgery: a single-center retrospective cohort study.

This study aimed to compare the outcomes of robotic-assisted rectal resection with conventional laparoscopic and open approaches, focusing on complication rates, conversion rates, length of hospital stay, and oncologic outcomes. A retrospective single-center cohort study included 106 patients with non-metastatic rectal cancer (UICC stages I-III) who underwent rectal resection from January 2013 to December 2023. Patients were assigned to open surgery (n = 23), conventional laparoscopic surgery (n = 55), or robotic-assisted surgery (n = 28). Robotic surgery demonstrated significantly lower conversion rates compared to minimal-invasive surgeries (p = 0.047) and shorter hospital stays (11.5 ± 8days) compared to open (17.91 ± 12days) and laparoscopic (17.2 ± 14days) surgeries (p = 0.001). The quality of the specimen was significantly better (Score 1) in robotic (85.71%) and open (89.09%) cases compared to laparoscopic approaches (47.83%) (p < 0.001). Laparoscopic surgery was identified as a risk factor for worse specimen quality (p < 0.001). Older patients (> 63years) had a higher risk for conversion in univariate analysis (p = 0.049). Morbidity was comparable between the groups (p = 0.131), and the anastomotic leakage rate did not differ significantly (laparoscopic: 18.18%, open: 13.04%, robotic: 17.86%). Kaplan-Meier survival curves showed no significant differences in overall survival probabilities among the groups. Robotic-assisted rectal resection provides significant advantages in terms of lower conversion rates, better specimen quality, and shorter hospital stays while maintaining comparable complication rates and oncologic outcomes to conventional laparoscopic and open approaches. These findings support robotic surgery as a standard treatment option for rectal cancer.

Effect of complete transurethral resection on oncologic outcomes after radiation therapy for muscle-invasive bladder cancer.: Transurethral resection in radiation therapy.

To compare the oncologic outcomes of patients with non-metastatic muscle-invasive bladder cancer (MIBC) undergoing complete versus incomplete transurethral tumor resection (TURBT) prior to radiation therapy. Patients with non-metastatic MIBC who underwent curative-intent radiation therapy between 2002 and 2018 at ten Canadian institutions were retrospectively evaluated. Inverse probability of treatment weighting was performed using baseline characteristics. Differences in survival outcomes by complete and incomplete TURBT were analyzed. Of the 757 patients included, 66% (498) had documentation of a complete and 34% (259) an incomplete TURBT. Before adjustment, 121 (47%) and 45 (9%) patients who underwent incomplete and complete TURBT, respectively, were diagnosed with cT3-4 tumor (p < 0.001). After weight-adjustment, all baseline cohort characteristics were balanced (absolute standardized differences < 0.1). The adjusted median follow-up was 27 months. Adjusted survival analyses showed no significant difference in 5-year overall survival (48% vs 52%, 1.03 [0.82-1.29]; p = 0.8), cancer-specific survival (64% vs 61%, 0.93 [0.70-1.25]; p = 0.7), metastasis-free survival (43% vs 46%, 0.97 [0.79-1.19]; p = 0.8), and disease-free survival (32% vs 35%, 0.95 [0.79-1.15]; p = 0.7) between the two groups. Complete TURBT may be associated with clinical organ-confined disease. Extent of TURBT was not independently associated with oncologic outcomes in patients with MIBC treated with radiation therapy.