Node Involvement Research Articles

Postoperative radiotherapy improves survival in completely resected non-small cell lung cancer with pathologic N2 stage IIIA and positive lymph node count greater than one: a SEER-based retrospective cohort study

ObjectiveNon-small cell lung cancer (NSCLC) constitutes approximately 85% of lung cancer cases, with 20%–30% of patients diagnosed at stage III. While multimodal therapy is the standard for treating locally advanced NSCLC, the role of PORT remains controversial. This study seeks to evaluate the effect of postoperative radiotherapy (PORT) on overall survival (OS) and cancer-specific survival (CSS) in patients with resected pathologic N2 (pN2) stage IIIA NSCLC.MethodsData from the Surveillance, Epidemiology, and End Results Program (SEER) 17 registry (2010–2019) were analyzed. The cohort included 1,471 patients aged 65 years or older, diagnosed with stage IIIA pN2 NSCLC, who had undergone lobectomy or total pneumonectomy. Patients who had received neoadjuvant chemotherapy or radiotherapy were excluded. Univariate and multivariate analyses were conducted to assess the association of PORT with OS and CSS. Kaplan-Meier survival curves were employed to estimate survival outcomes, while the COX proportional hazards model was utilized for comparative analysis. PLN counts were stratified into two categories: ≤1 and >1.ResultsAmong the 1,471 patients included in the study, 613 (41.67%) received PORT, while 858 (58.33%) did not. PORT was associated with a significantly higher 1- and 3-year OS (89.96% and 68.49%, respectively) compared to the non-PORT group (87.44% and 61.88%, respectively, P = 0.03). However, no significant difference in CSS was observed between the groups (P = 0.15). Among patients with PLN counts >1, PORT significantly improved OS (HR = 1.32, 95% CI = 1.04–1.68, P = 0.0016) and CSS (HR = 1.32, 95% CI = 0.99–1.70, P = 0.026), whereas no significant differences were seen in patients with PLN counts ≤1.ConclusionsThis study underscores the potential of PORT in enhancing OS in patients with resectable pN2 stage IIIA NSCLC, particularly in those with PLN counts exceeding one. These findings suggest that PORT may offer improved outcomes in patients with extensive lymph node involvement, emphasizing the need for further prospective studies to validate and expand upon these observations.

Systematic literature review (SLR) of prognostic factors (PFs) in locally advanced rectal cancer (LARC) and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer (RC).

303 Background: Innovative immunotherapies arebeing developed to improve clinical outcomes in patients (pts) withdMMR/MSI-H LARC who respond poorly to the current standard of care. A comprehensive overview of PFs in dMMR/MSI-H LARC may provide insight into the natural history of this disease to inform clinical study design and pt risk stratification. Methods: Systematic searches of bibliographic databases (EMBASE, MEDLINE, Cochrane; 2013–2023) and congress websites (2021–2023) were conducted to identify PFs for tumor response and survival outcomes in adult pts with LARC (SLR1) and dMMR/MSI-H RC (SLR2). Given the expected high volume of evidence, SLR1 was limited to large observational studies (≥1000 pts) and clinical trials (≥100 pts); SLR2 had no such limits. Results: 95 of 2307 publications met the inclusion criteria for SLR1. Of the PFs reported in ≥20 studies, older age, more lymph node involvement or fewer nodes assessed, higher T-stage or larger tumor size, higher histologic grade, and more comorbidities were most frequently significantly associated with poorer patient prognosis (Table). 3 of 289 publications met the inclusion criteria for SLR2. Neoadjuvant chemoradiation therapy (CRT) compared to chemotherapy (CT) was associated with statistically significant worse disease-free survival (DFS) and distant metastasis-free survival (DMFS), while T- or N-stage, age, and sex did not significantly impact these outcomes. Low vs middle tumor localization was also associated with worse DMFS. Stage III and IV disease were associated with worse RC-specific survival, while surgical procedure (segmental vs extended) showed no difference in overall survival (OS). The addition of neoadjuvant CRT or adjuvant CRT/CT to surgery alone had no impact on OS but was associated with worse DFS. Conclusions: Evidence regarding PFs in dMMR/MSI-H RC is scarce and may limit its interpretability, highlighting the need for further research that may be informed by the PFs identified from SLR1. The results from these SLRs may be helpful for optimizing patient management and treatment decision making, and to further contextualize RC clinical trials. PFs reported in ≥20 studies with ≥75% of studies reporting significant results in pts with LARC. PF Studies reporting PF (n) Studies reporting significant* impact of PF on prognosis (%) Poorer prognosis group Top 2 most frequently reported outcomes Age 59 81.4 Older OS, DFS Lymph node involvement/assessment 55 78.2 Yes or higher N stage OS, DFS T-stage or tumor size 53 79.2 Higher or larger OS, DFS Histologic grade 37 75.7 Higher OS, pathological complete response (pCR) Comorbidities 23 87.0 More OS, pCR *p-value <0.05 was considered significant as reported in the identified studies.

Perineural Invasion Unveiled: Deciphering the Prognostic Impact of Diameter and Quantity Subcategories in Oral Cancer.

Perineural invasion (PNI) is an established prognostic factor in oral squamous cell carcinoma (OSCC), but the impact of its subcategories on survival is not fully understood. This study quantifies the number and diameter of PNI foci to assess their prognostic relevance in OSCC. To evaluate the prognostic significance of PNI subcategories, specifically the number and diameter of PNI foci, as predictors of overall survival (OS) and disease-free survival (DFS) in OSCC patients. Retrospective cohort study, adhering to STROBE guidelines. Single-center study at MacKay Memorial Hospital, Taiwan, including patients diagnosed with OSCC from 2005 to 2018. Nine hundred twenty-six patients with biopsy-proven OSCC, excluding those with perioperative mortality or incomplete follow-up. Histological evaluation of PNI, including quantifying the number and diameter of invaded nerves, along with clinicopathological features such as tumor stage and lymphovascular invasion (LVI). OS and DFS, assessed via Cox proportional hazards models, Kaplan-Meier survival analysis, and receiver operating characteristic curve analysis for PNI foci subcategories. PNI was present in 138 (14.9%) patients and was significantly associated with adverse histologic features, advanced tumor stage, nodal involvement, metastasis, and LVI. Multivariate analysis revealed that both the number of PNI foci greater than 4 and nerve diameters exceeding 0.21 mm were significantly associated with poorer OS and DFS (P < .05). After adjusting for clinical variables, PNI remained an independent predictor of worse OS [hazard ratio (HR): 1.37] and DFS (HR: 1.46). PNI is a significant independent prognostic factor in OSCC. Patients with more than 4 PNI foci or nerve involvement greater than 0.21 mm in diameter experienced significantly worse survival outcomes. These findings suggest that detailed assessment of PNI subcategories should be incorporated into OSCC management, guiding treatment decisions and potentially informing the need for adjuvant therapies.

Total neoadjuvant therapy with FOLFOX plus bevacizumab and short-course radiotherapy for Ras mutant, high-risk, locally advanced rectal cancer: The TRAINER trial.

133 Background: Total neoadjuvant therapy (TNT) intensified by the combination of targeted therapy or immunotherapy is warranted to achieve satisfying local and systemic control for high-risk locally advanced rectal cancer (LARC). Our study aimed to explore the efficacy and safety of a FOLFOX-based TNT regimen plus bevacizumab and short-course radiotherapy (SCRT) in Ras-mutant high-risk LARC patients. Methods: In this single-arm, single-center, phase II trial, LARC patients with at least one risk factor (cT3c-4, mesorectal fascia positive, cN2, lateral lymph node involvement, and extramural venous invasion positive) were recruited and only Ras-mutant patients were included. Four cycles of FOLFOX plus bevacizumab were arranged as induction chemotherapy followed by SCRT (25Gy/5Fx) and two cycles of FOLFOX as consolidation chemotherapy. Surgery was performed 8 weeks after completion of radiotherapy. After surgery, high-risk stage III patients (T4 or N2) were recommended to receive an extra 6 cycles of FOLFOX as adjuvant chemotherapy, while low-risk stage III patients were scheduled for regular follow-up. Patients with clinical complete response(cCR) were allowed to choose the “Watch &amp; Wait” (W&amp;W) strategy instead of surgery. The primary endpoint was the complete response (CR) rate, defined as the total rate of cCR plus pathological complete response (pCR). Secondary endpoints included adverse events of TNT, postoperative complications, 2-year disease-free survival, and overall survival. Results: Between April 2, 2021, and March 12, 2024, 47 of 51 enrolled patients were eligible for treatment. All patients completed the prescribed TNT cycles, and six (12.8%) of them had dose reduction. The CR was achieved in 18 (38.3%) patients, including 14 (29.8%) pCR. No grade IV-V toxicity was observed and the incidence of grade III toxicities was 34.0%. Four patients (8.5%) achieved cCR and chose the W&amp;W strategy. The other 43 patients underwent curative surgery and anal preservation was achieved in 39 (90.7%) patients. Seven patients (16.3%) experienced postoperative complications, including four (9.3%) cases of anastomotic leakage. Conclusions: The intensified TNT regimen combined with bevacizumab achieved a satisfying CR rate with acceptable toxicities and complications for Ras-mutant high-risk LARC patients. Long-term survival data of this cohort are needed to validate the efficacy of this regimen further. Clinical trial information: NCT04923620 .

Clinical outcomes of hypofractionated radiotherapy (5x5 Gy) with a simultaneous integrated boost (5x6 Gy) in locally advanced rectal cancer.

60 Background: Hypofractionated RT (5x5 Gy) with or without subsequent chemotherapy is a standard of care used at the National Institute of Oncology, Warsaw, Poland, as a preoperative treatment for locally advanced rectal cancer. To maximize the chance of achieving a complete response (CR), when surgery is not planned or when there are clinically involved lymph nodes located outside the standard TME field, RT can be augmented with a simultaneous integrated boost (SIB) delivering 5x6 Gy. This report aims to evaluate the clinical outcomes of hypofractionated RT with a SIB in rectal cancer. Methods: From Dec 2018 to Sep 2022, 78 consecutive pts with a median age of 67 years (range 36–89 years), received hypofractionated RT utilizing the SIB-VMAT technique. The radiation dose fractionation was 5x5 Gy to the rectum, mesorectum and elective lymph nodes and a SIB to the GTV for a total dose of 30 Gy. Results: 30 pts (38.5%) received a SIB for the rectal tumor, of which 15 pts (19.2%) were deemed unfit for surgery, 10 pts (12.8%) refused surgical treatment, 3 pts (3.8%) had an oligometastatic disease, and 2 pts (2.6%) had an advanced primary tumor. 48 pts (61.5%) received a SIB to the clinically involved lymph nodes located outside the standard TME field. All 78 pts completed RT as planned without interruptions or dose modifications and with an acceptable toxicity profile. There was a 26.9% (n = 21) incidence of G2 toxicities (diarrhea, proctitis, skin toxicity, cystitis or lumbosacral plexus neuropathy) and a 3.8% (n = 3) incidence of G3 toxicities (diarrhea or proctitis). After a median follow-up of 917 days (range 33–1927 days), an assessment of response was conducted in 68 cases. In 94.1% (n = 64) there was no progression at the site irradiated to a dose of 30 Gy. After completion of RT, mr-TRG was evaluated in 28 pts. In 46.4% (n = 13) mr-TRG 1-2 (cCR) was achieved. Of the 24 pts qualified for the watch and wait strategy, 17 had follow-up. Of this group, 64.7% (n = 11) remained progression-free, and 11 pts had an adequate evaluation for cCR (imaging and endoscopy), resulting in a 63.6% (n = 7) rate of cCR. 43 pts underwent surgery, of which 97.7% (n = 42) had R0 resection. In 41 cases pathological TRG was assessed according to AJCC or Ryan, of which 41.4% (n = 17) achieved TRG 0-1 (pCR). In 40 cases the operated pts had no initial metastatic spread, among them 67.5% (n = 27) remain disease-free. 67 pts reported disease-related symptoms before RT. After treatment, 89.6% (n = 60) of those pts achieved symptomatic improvement in either rectal bleeding, bowel frequency, or pain control. Conclusions: Hypofractionated RT with SIB-VMAT delivering a dose of 30 Gy/25 Gy/5 fractions provides good local control and is a safe and viable option for both young and elderly patients who will not undergo surgery and for patients with involved lymph nodes located outside the standard TME field to maximize the chance of achieving CR.

Rethinking the definition of stage III disease in adrenocortical carcinoma: Assessing the impact of clinical lymph node positive disease.

Stage III adrenocortical carcinoma encompasses both lymph node positive (TanyN1M0) and negative (T3-4N0M0) disease. Given the disease's rarity, the current staging paradigm's estimates of survival are supported by limited evidence. Consequently, we examined the impact of clinical lymph node positivity on survival outcomes in the context of the current staging of advanced adrenocortical carcinoma. We identified patients with clinical stage III and IV disease from the National Cancer Database. Kaplan-Meier methods and Cox proportional hazards models estimated overall survival for stage III lymph node negative, stage III lymph node positive, and stage IV disease. We identified 917 patients with adrenocortical carcinoma - 322 (35.1%) stage III lymph node negative, 67 (7.3%) stage III lymph node positive, and 528 (57.6%) stage IV. 3-year overall survival for patients with stage III lymph node negative, stage III lymph node positive, and stage IV disease was 48.6%, 29.4%, and 15.6%, respectively. On univariable analysis, patients with stage III lymph node positive disease were associated with worse survival than those with stage III lymph node negative disease (HR 1.72, 95% CI 1.26-2.37, P < 0.001); however, this relationship did not maintain significance in multivariable analysis (HR 1.27, 95% CI 0.88-1.83, P = 0.21). Our study finds that patients with clinical stage III lymph node positive adrenocortical carcinoma may have worse survival outcomes than stage III patients without lymph node involvement. The results of this study suggest the need for an updated, more nuanced staging paradigm, which differentiates stage III disease by lymph node positivity.

The Impact of Prognostic Factors on Survival in Patients with Non-Metastatic Invasive Breast Cancer: A Single-Center Experience

Background: Breast cancer (BC) is the most prevalent and lethal cancer in women. Prognostic factors are used to guide treatment and predict the prognosis. This study aims to assess the influence of prognostic factors on the survival of patients with non-metastatic invasive BC. Methods: Data from invasive BC patients admitted to Medical Oncology Department of Süleyman Demirel University between October 2002 and October 2013 were retrospectively reviewed. Clinicopathologic features, treatment information, and follow-up data were noted. The Kaplan-Meier method was used to estimate survival functions. Multivariate Cox regression analysis was performed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS), with p values &lt;0.05 for univariate results Results: A total of 717 patients entered the study. The median follow-up time was 41 months. Recurrence was detected in 17.4% of the patients, and 111 (15.5%) patients died. The 5- and 10-year DFS rates were 78% and 61%; OS rates were 86% and 70%, respectively. In multivariate analyses, DFS and OS were associated with axillary lymph node involvement (P&lt;0.001 and P&lt;0.05, respectively), tumor size (P&lt;0.05), and histologic grade (P&lt;0.05); whereas human epidermal growth factor receptor 2 positivity had only a statistically significant effect on poor OS (P=0.004). Conclusion: Comparable to previous studies, traditional prognostic factors had an important impact on prognosis in invasive BC patients. In the current era, where more conservative surgical approaches and new, effective systemic neoadjuvant and adjuvant therapies are widely used, the importance of the traditional prognostic factors highlighted in our study needs to be established by further studies.

Head and neck cancer registry of Japan.

The Head and Neck Cancer Registry, supported by the Japan Society for Head and Neck Cancer, was re-established in 2012 after renewal of the contents and methods of registration. The registry registers patients with previously untreated, histologically confirmed malignant tumors of the head and neck, including the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, nasal cavity and paranasal sinus, major salivary gland, and cervical nodal involvement with an unknown primary. The total number of registered patients reached more than 150,000 as of June 2024. We have published reports of important real-world evidence from the registry data. We believe that this nation-wide, organ-based registry aids understanding of the epidemiology and treatment strategies of head and neck cancer, in addition to hospital-based and national cancer registries in Japan.

Whole-body magnetic resonance imaging provides accurate staging of diffuse large B-cell lymphoma, but is less preferred by patients.

Whole-body magnetic resonance imaging (wbMRI) allows general assessment of systemic cancers including lymphomas without radiation burden. To evaluate the diagnostic performance of wbMRI in the staging of diffuse large B-cell lymphoma (DLBCL), determine the value of individual MRI sequences, and assess patients' concerns with wbMRI. In this single-center prospective study, adult patients newly diagnosed with systemic DLBCL underwent wbMRI on a 3T scanner [diffusion weighted images with background suppression (DWIBS), T2, short tau inversion recovery (STIR), contrast-enhanced T1] and fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) (reference standard). The involvement of 12 nodal regions and extranodal sites was evaluated on wbMRI and PET/CT. The utility of wbMRI sequences was rated on a five-point scale (0 = not useful, 4 = very useful). Patients received a questionnaire regarding wbMRI. Of 60 eligible patients, 14 (23%) were enrolled and completed the study. The sensitivity of wbMRI in the nodal involvement (182 nodal sites) was 0.84, with 0.99 specificity, positive predictive value of 0.96, negative predictive value of 0.97, and 0.97 accuracy. PET/CT and wbMRI were concordant both in extranodal involvement (13 instances) and staging (κ = 1.0). The mean scores of the utility of MRI sequences were 3.71 ± 0.73 for DWIBS, 2.64 ± 0.84 for T1, 2.14 ± 0.77 for STIR, and 1.29 ± 0.73 for T2 (P < 0.0001). Patients were mostly concerned about the enclosed environment and duration of the MRI examination (27% of patients). The wbMRI exhibited excellent sensitivity and specificity in staging DLBCL. DWIBS and contrast-enhanced T1 were rated as the most useful sequences. Patients were less willing to undergo wbMRI as a second examination parallel to PET/CT, especially owing to the long duration and the enclosed environment.

Propensity score matched comparison of lymph node upstaging in early-stage lung cancer: open versus minimally invasive surgery with standardized lymphadenectomy

BackgroundLymph node upstaging represents a quality criterion for standardized lymphadenectomy in lung cancer surgery. The aim of the study was to compare whether the quality of standardized lymphadenectomy in lung cancer surgery is comparable in minimally invasive (video-assisted thoracoscopic surgery) and the open approach (thoracotomy). Furthermore, factors associated with lymph node upstaging were assessed, as was its impact on overall survival and progression-free survival.MethodsThis retrospective study reviewed data of all patients undergoing lobectomy at the Lung Tumor Center Munich between 2011 and 2020. Inclusion factors were non-small cell lung cancer without nodal involvement (N0) or metastasis (M0) and standardized lymphadenectomy. A propensity score matched analyses was performed. Frequency of categorical outcomes was compared with Chi [2]-test, mean values with t-test. We used logistic and Cox regression models to assess factors associated with upstaging, overall survival and progression-free survival, restrictively.ResultsOf 1691 patients undergoing lobectomy, 637 met our inclusion criteria. After propensity score matching 198 patients remained in each group. Univariate analysis showed no significant difference in lymph node upstaging between the two groups. (p = 0.12). Overall affected lymph nodes (p = 0.45) and overall affected lymph node stations (p = 0.26) were not significantly different. Multivariate Cox regression analysis showed that overall survival and progression free survival were also independent of the surgical approach. L1 status was the only factor associated with progression-free survival.ConclusionMinimally invasive approaches achieves comparable lymph node upstaging in patients undergone standardized lymphadenectomy.

Abstract A004: Nodal Management in cancer treatment: Synergistic potential of immune checkpoint inhibitors

Abstract Lymph nodes (LNs) are critical components of the immune system, playing an essential role in the regulation of tumor immune surveillance and the progression of metastatic cancer. Recent advancements in immune checkpoint inhibitors (ICIs), including monoclonal antibodies targeting PD-1, PD-L1, and CTLA-4, have revolutionized cancer therapy by enhancing the immune system's ability to recognize and eliminate tumor cells. However, the interaction between immune checkpoint blockade (ICB) and lymphatic tissue, particularly the role of regional lymph nodes in treatment efficacy, remains insufficiently understood. This research explores the potential of combining immune checkpoint therapy with targeted strategies for managing nodal involvement in cancers. We aim to investigate the mechanisms by which tumor-infiltrating lymph nodes may either aid or hinder the response to ICBs, with a focus on the activation of anti-tumor immune responses within the nodal microenvironment. By examining how immune checkpoints impact tumor-associated lymphoid structures, we aim to identify strategies for improving regional lymph node management, including the use of neoadjuvant ICB, lymph node dissection, and lymph node-targeted drug delivery. The findings of this study may provide insights into optimizing immune checkpoint blockade therapies for cancers with extensive nodal metastasis and lead to novel therapeutic approaches that enhance regional immune responses while minimizing adverse effects. Ultimately, this research has the potential to contribute to a more personalized approach to cancer treatment, particularly for patients with advanced or metastatic disease, where nodal involvement is often a critical determinant of prognosis. Citation Format: Su-Jin Koh. Nodal Management in cancer treatment: Synergistic potential of immune checkpoint inhibitors. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A004.

Abstract IA03: Tumor draining lymph nodes: Friends or foes

Abstract Nodal metastasis is the most common pattern of spread in head and neck squamous cell carcinoma (HNSCC). Nodal involvement has been linked to tumor aggressiveness and poor prognosis as reflected in the staging system. It also leads to the current surgical and radiation managements of HNSCC that include elective nodal treatment in addition to addressing gross disease. Yet, elective nodal treatment (either with surgery or radiation) has been linked to immune suppression since the tumor-draining lymph nodes (TDLN) are crucial for the development of a tumor-directed adaptive immune response, particularly in T-cell priming. Here I will touch on some recent work showing: (1) how nodal metastasis can influence tumor distant spread; (2) potential role of B cells in the TDLNs in driving anti-tumor T cell immunity through the recognition of extracellular vesicle-linked antigens, (3) potential treatment approaches of HNSCC that can mitigate the negative consequences of targeting TDLN. Citation Format: Quynh-Thu Le. Tumor draining lymph nodes: Friends or foes. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA03

Grading systems and perineural invasion in oral squamous cell carcinoma - a disease-specific survival analysis.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer, with prognosis influenced by clinical variables as well grading systems and perineural invasion (PNI), which are associated to poorer outcomes, including higher rates of recurrence and metastasis. This study aims to evaluate OSCC using three grading systems and assess the impact of PNI and clinicopathologic parameters on patient survival. Eighty-one primary OSCC samples were analyzed. Histopathological evaluations were performed utilizing Malignancy Grading of the Deep Invasive Margins, WHO grading system, and the Histologic Risk Assessment. S-100 immunohistochemistry was used to detect PNI. Five-year disease-specific survival (DSS) curves were generated using the Kaplan-Meier method, and the Cox proportional hazards model analyzed prognostic significance. Advanced clinical stage was significantly associated with reduced survival (p-value <0.001, HR = 4.07). Patients without regional lymph node involvement had better survival (p-value 0.002, HR = 0.37). Higher histologic risk assessment scores were linked to worse outcomes. Multifocal neural invasion significantly correlated with poorer survival compared to unifocal invasion (p-value 0.017, HR = 4.20). Patients undergoing surgery followed by adjuvant therapies had better survival rates. Besides clinical stage and histological grade, PNI also showed to be a crucial prognostic factor in OSCC, necessitating aggressive treatment strategies.

Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p &lt; 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p &lt; 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p &lt; 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p &lt; 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p &lt; 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p &lt; 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p &lt; 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p &lt; 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p &lt; 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p &lt; 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p &lt; 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p &lt; 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p &lt; 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p &lt; 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p &lt; 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p &lt; 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p &lt; 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p &lt; 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p &lt; 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.

A Multicenter Study on the Relationship of Tumor Lesion Location with Bilateral Parametrial Involvement and Pelvic Lymph Node Metastasis in Cervical Squamous Cell Carcinoma.

This study aimed to explore the relationship of cervical tumor lesion location (CTLL) with bilateral parametrial involvement (PI) and pelvic lymph node metastasis (LNM). The study retrospectively analyzed the clinicopathologic and imaging data of patients with cervical squamous cell carcinoma (SCC) retrieved from multiple centers. According to the CTLL, patients were allocated to three groups: a middle one third group, a unilaterally dominant group, and the entire-region group. Uni- and multivariate logistic regression analyses were performed to explore the preoperative risk factors related to PI and pelvic LNM. The rates of PI and pelvic LNM at the tumor-ipsilateral side and the tumor-contralateral side were compared using the Wilcoxon test. The study enrolled 776 cases. The CTLL was an important preoperative risk factor for both PI and pelvic LNM. Parametrial involvement occurred solely on the tumor-ipsilateral side (3.57 %) in the unilaterally dominant group, whereas the rate of pelvic LNM on the tumor-ipsilateral side was 11.22 %, significantly higher than on the contralateral side (5.1 %), with no pelvic LNM found on the tumor-contralateral side of patients with tumors smaller than 3.5 cm. Cervical SCC exhibits the characteristic of more accessible tumor-ipsilateral PI and pelvic LNM. When evaluation by magnetic resonance imaging (MRI) shows that the tumor lesion does not involve the contralateral one third of the cervix, a reduction in the resection scope of the contralateral parametrium can be considered, avoiding resection of the para-aortic lymph nodes, and if the tumor is smaller than 3.5 cm, a reduction in the resection scope of the tumor-contralateral pelvic lymph nodes also can be considered.

SABR tolerance after prostatectomy: pushing the boundaries of ultrahypofractionation.

To evaluate the feasibility and tolerance of ultra-hypofractionated SABR (stereotactic ablative radiation therapy) protocol following radical prostatectomy. We included patients undergoing adjuvant or salvage SABR between April 2019 and April 2023 targeting the surgical bed and pelvic lymph nodes up to a total dose of 36.25 Gy (7.25 Gy/fraction) and 26 Gy (5.2 Gy/fraction), respectively, in 5 fractions on alternate days with an urethra sparing protocol. Acute and late adverse effects were assessed using the CTCAE v5.0. Pearson's chi-square test for categorical variables was used to compare characteristics and possible associations among different subgroups. Adjuvant radiation therapy (ART) was administered to 40 high-risk patients (detectable post-surgery PSA, Grade Group 4/5, nodal involvement, R1/R2 resection margin), while salvage radiotherapy (SRT) was delivered to 60 patients with rising PSA levels post-undetectable values. Elective nodal irradiation was performed in 57 patients, with 11 additional patients receiving a simultaneous integrated boost (total dose: 40 Gy in 5 fractions) for macroscopic nodal disease. Twenty-four high-risk patients underwent 24-months androgen deprivation therapy (ADT). Treatment was well-tolerated with minimal toxicity. The maximum grade of SABR-related toxicity observed was grade 3. Acute gastrointestinal (GI) toxicity included seven cases of grade 2 and one of grade 3, while acute genitourinary (GU) events were limited to grade 2 in eight patients. Early-late toxicity included two cases of grade 3 and seven of grade 2 for GI, and 11 cases of grade 2 for GU. No toxicity above grade 3 was reported. With a median follow-up of 24 months (6-60 months), 14 patients experienced disease recurrence. Ultra-hypofractionated adjuvant/salvage SABR appears feasible and safe. Longer follow-up is needed to validate observed outcomes.

Clinicopathological study and molecular subtyping of muscle-invasive bladder cancer (MIBC) using dual immunohistochemical (IHC) markers

BackgroundMuscle-invasive bladder carcinomas (MIBCs) exhibit significant heterogeneity, with diverse histopathological features associated with varied prognosis and therapeutic response. Although genomic profiling studies have identified several molecular subtypes of MIBC, two basic molecular subtypes are identified - luminal and basal, differing in biological behaviour and response to treatment. As molecular subtyping is complex, surrogate immunohistochemical (IHC) markers have been used to determine the molecular subtypes with good correlation to genomic profiling.MethodsWe analysed the clinicopathological features of 66 cases of MIBCs received over a 5-year study period. IHC expression was determined using GATA3 and CK5/6 to classify MIBC into luminal, basal and double-negative subtypes. The association between clinicopathologic variables and molecular subtypes were analysed using Chi-square test.ResultsThe mean age at diagnosis of MIBC was 65.91 years with a male predominance. Based on IHC expression of GATA3 and CK5/6, MIBCs were classified into luminal, basal and double negative subtypes in 62.1%, 30.3% and 7.6% respectively. The luminal subtype occurred at an older age and showed predominantly conventional urothelial carcinoma with papillary morphology. Basal subtype occurred at earlier age, showed greater association with smoking and was more commonly associated with urothelial carcinoma with non -papillary morphology and exhibiting divergent differentiation as well as pure squamous cell carcinoma on histopathological examination. The double-negative subtype was found exclusively in males and exhibited a non-papillary morphology. Notably, all diagnosed neuroendocrine carcinomas were classified as double-negative type. While there was no statistically significant difference in tumour stage in cystectomy specimens between the molecular subtypes, lympho-vascular invasion and lymph node metastasis was more commonly associated with the basal type (p < 0.05) There was no significant difference in recurrence rates, metastasis and death between luminal and basal subtypes.ConclusionA simple two-antibody panel using GATA3 and CK5/6 could help in classifying MIBC into basic molecular subtypes of MIBC with distinctive histopathological features that can provide insights into the corresponding molecular subtype. Greater association of lymphovascular invasion and lymph nodal involvement in cystectomy specimens in basal type and distant metastasis in the double-negative subtype suggests a more aggressive clinical behaviour of these, necessitating more intensive treatment.

Randomized Evaluation of the PET-Adjusted IMRT for NSCLC Trial (REPAINT).

Standard radiotherapy (RT) for locally advanced NSCLC (LA-NSCLC) employs a uniform dose of approximately 60 Gy. Recent trials demonstrated that radiotherapy dose escalation may not improve outcomes and may cause added toxicity. XXX previously performed a single-arm trial testing a personalized, risk-adapted, and de-intensified RT strategy. We now report findings from a randomized trial testing this novel approach. LA-NSCLC patients with ECOG performance status 0-2 were eligible for this trial. Metabolic tumor volume (MTV) for each pulmonary tumor and involved lymph node was calculated using FDG-PET. Participants were randomized 1:1 to receive standard RT (60 Gy in 30 fractions delivered to pulmonary tumors and involved lymph nodes) versus dose-painted RT (55 Gy delivered to tumors and lymph nodes with metabolic volume exceeding 20 cm3 and 44-48 Gy to other lesions, all in 20 fractions). Concurrent chemotherapy and standard adjuvant therapy were given in both arms. The primary objective was to characterize patient-reported outcomes utilizing PRO-CTCAE. Secondary objectives included comparing outcomes between study arms. Fifty patients were enrolled. The most common grade 3 patient-reported adverse events within 90 days of RT completion were dysphagia (38%), fatigue (38%), cough (32%), and wheezing (28%). The median progression-free survival (PFS) duration is 18 months, and the median overall survival (OS) duration is 42 months. PFS and OS rates are similar across study arms (logrank p=0.562 and 0.765, respectively). There have been three cases of in-field disease progression, with one in the control arm and two in the dose-painted arm. Grade 3-4 lymphopenia was reduced with dose-painted RT (48% v. 81%, chi-square p=0.012). High-grade patient-reported toxicity in LA-NSCLC patients who are treated with concurrent chemoradiotherapy is common. We found no evidence that risk-adapted radiotherapy de-escalation compromises clinical outcomes. Follow-up studies testing the ability of this approach to improve the safety profile of chemoradiotherapy are warranted.

Surgical Management of Gastroenteropancreatic Neuroendocrine Tumors

Background/Objectives: Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. Methods: A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. Results: For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored for smaller and low-grade lesions. Small bowel NETs can be multifocal and thus often require a surgical approach with careful evaluation of the entire intestine. Pancreatic NETs are categorized as functional or non-functional, with enucleation or formal resection strategies based on size, location, functional status, and risk of malignancy. Colorectal NETs are primarily treated with transanal localized or formal surgical resection, depending on lesion size and depth of invasion or presence of lymph node involvement. Appendiceal NETs are either treated with appendectomy or right hemicolectomy, depending on the size, location, and invasiveness of the lesions. For metastatic NETs, cytoreduction, liver transplantation, and targeted therapies offer symptom relief and possible survival benefits. Conclusions: Surgical resection provides curative potential for localized NETs and symptom control in metastatic cases. Future research is essential to refine guidelines for intermediate-risk lesions and multifocal tumors, ensuring optimal outcomes for patients with gastroenteropancreatic NETs.

Lymph Node Staging and Treatment in Pediatric Patients With Soft Tissue Sarcomas: A Consensus Opinion from the Children's Oncology Group, European paediatric Soft tissue sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe.

Accurate staging of nodal involvement in pediatric sarcoma patients is important to determine correct systemic and local therapy, with the goal to reduce subsequent recurrences. However, differences in lymph node staging strategies, definitions, and treatment protocols between the Children's Oncology Group (COG), European paediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS) complicate comparisons. In this article, we aim to establish internationally recognized recommendations for lymph node assessment and treatment of children and adolescents diagnosed with rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) according to the Consensus Conference Standard Operating Procedure methodology.