Pathologic Lymph Node Involvement Research Articles

COVID-19 pandemic impact on uro-oncological disease outcomes at a German referral center.

To assess differences in referral and pathologic outcomes for uro-oncology cases prior to, during and after the Covid-19 pandemic, comparing clinical and pathological data from cancer surgeries performed at a university medical center between 2018 and 2023. We collected data of 212 patients with radical prostatectomy (RP) for prostate cancer (PCa), 157 patients with radical cystectomies (RC) for bladder cancer (BCa), 36 patients with radical nephroureterectomies (RNU) for upper tract urothelial carcinoma (UTUC), 133 patients with partial nephrectomies (PN) and 160 patients with radical nephrectomies (RN) for renal cancer, 93 patients with orchifunicolectomy for testicular cancer, 39 patients with newly diagnosed penile cancer. Data from patients treated between 2018 to February 2020 (before the Covid-19 pandemic) were compared with data from patients treated between March 2020 and March 2022 (during the Covid-19 pandemic) and between April 2022 and February 2023 (after the Covid-19 pandemic). No differences in terms of main pathologic features were observed in patients undergoing RP, RNU, orchifunicolectomy, or circumcision and/or penectomy. Further a lower pathological tumor stage were diagnosed for RN after the Covid-19 pandemic (p<0.05). A higher age at diagnosis for penile cancer was observed during the pandemic cohort in comparison to the pre-Covid-19 pandemic cohort (p<0.05), but this did not translate into a worse pathological stage or lymph node involvement. Another notable change was the shortening of the length of stay (LOS) for orchifunicolectomy over the pandemic (p<0.05). Neither decline in uro-oncologic activity nor pathological features were observed at our institution before, during and after the Covid-19 pandemic. A significantly lower pathological tumor stage for RN after the Covid-19 pandemic was seen. Penile cancer was diagnosed at a significantly higher age during the Covid-19 pandemic, and a decrease in LOS for orchifunicolectomy was observed.

Frequency of KRAS and BRAF mutations in colorectal carcinoma and their association with clinical-pathological characteristics in a tertiary hospital in Kenya.

Colorectal carcinoma is a leading cause of cancer morbidity and mortality globally. Its management includes the use of targeted therapy which require assessment for biomarkers to choose eligible patients. KRAS and BRAF mutations are biomarkers predictive of response to anti-EGFR therapy. This study aimed at determining the frequency of BRAF V600E and KRAS exon 2,3,4 mutations in colorectal carcinoma patients at the Aga Khan University Hospital Nairobi, Kenya. Study participants were patients who had colectomy for colorectal carcinoma. They were identified from the laboratory information system. The patients age, gender and tumor location were determined from the medical records. The histological diagnosis, pathological tumor and nodal stage were confirmed by examining hematoxylin and eosin-stained slides prepared from the colectomy specimen. DNA was extracted from the specimens using Qiagen QIAamp DNA FFPE Tissue Kit and PCR performed using EntroGen KRAS/BRAF mutation analysis kit following manufacturer's protocol. One hundred fourteen patients were enrolled. Colorectal carcinoma was significantly more common in males than females. The mean age at diagnosis was 58 years. Majority of the tumors were in the right colon, were of pathological tumor stage T3 and had nodal involvement. Forty six percent (46%) of the cases had KRAS mutations while 5.3% had BRAF V600E mutation. KRAS mutation was associated with a high pathological tumor stage and nodal involvement. Colorectal carcinoma in our patients is more common in males and tend to occur at a younger age. The patients tend to have a high tumor pathological stage and nodal involvement at diagnosis. The high frequency of KRAS exon 2,3,4 mutation and low frequency of BRAF V600E mutations is similar to what has been reported in literature.

Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy

IntroductionThe significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST.MethodsThis retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model.ResultsOf the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42–2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12–4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%).ConclusionsSLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.

The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis.

Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56-66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0-100%), 40% (0-77%), and 31% (0-75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89-94%), 89% (95% CI, 86-93%), and 84% (95% CI, 73-92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70-83%), 67% (95% CI, 60-74%), and 61% (95% CI, 55-67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79-88%), 75% (95% CI, 72-79%), and 68% (95% CI, 62-74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3-14%). PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.

Personalized cell-free tumor DNA analysis for patients with HNSCC: Liquid biopsy for minimal residual disease detection in head and neck squamous cell carcinoma (LIONESS).

3010 Background: Early relapse and development of metastatic disease are some of the primary reasons for the poor prognosis of patients with head and neck squamous cell carcinoma (HNSCC). We conducted LIONESS, a single-center prospective cohort study to assess ctDNA in plasma and saliva from 76 patients with HNSCC receiving primary surgery with curative intent. Our objectives were to determine whether postoperative ctDNA detection can act as a biomarker for surgical tumor clearance and detection of molecular residual disease (MRD) and to evaluate the potential of tumor-informed ctDNA analysis for early molecular-level detection of relapse or prior to clinically confirmed recurrence. Methods: Plasma and saliva samples from 76 HNSCC patients (37% stage I/II, 63% stage III/IV; 93% p16-negative) were collected pre- and postoperatively and during clinical follow-up. Whole exome sequencing was performed on FFPE tumor tissue. Tumor-specific variants for personalized assay design (RaDaR, NeoGenomics Laboratories) were selected and used in the analysis of serial samples for evidence of MRD. ctDNA levels were correlated to tumor volumes from staging CT, as well as pathological and other clinical parameters. Results: 617 longitudinal plasma and 128 saliva samples were collected pre- and postoperatively and during clinical follow-up (median follow-up time of 805 days). In plasma, ctDNA was detected at a median estimated variant allele frequency (eVAF) of 0.036% (0.000327% - 18.43%). 34% of positive samples had ctDNA levels detected at an eVAF of ≤0.01%. Increased plasma ctDNA levels were detected postoperatively in 96% of cases with confirmed clinical recurrences (21/22) with a median lead time of 160 days (6 – 763 days). Of the remaining 54 patients with no clinically confirmed relapse, ctDNA was detected immediately postop in 7 of them. In 5 patients, adjuvant therapy resulted in persistent ctDNA clearance, while 2 patients are deceased. ctDNA was also detected in baseline saliva samples from patients with HNSCC of various anatomical locations with a 74% overlap with the corresponding plasma ctDNA profiles. There was a strong linear correlation between larger tumor volumes and higher eVAF and a trend towards higher eVAF in cases with regional and distant recurrences in comparison to local relapse. Pathological tumor stage and lymph node involvement were both strongly correlated with preoperative ctDNA shedding. Conclusions: The use of ctDNA detection in surgically treated patients with HNSCC has significant potential to guide treatment decisions, improve disease outcome and potentially spare patients unnecessary, partially invasive interventions during clinical follow-up. Our work demonstrates the feasibility of tumor-informed ctDNA assays for detection of MRD postoperatively and for monitoring for early detection of relapse.

Minor (≤ 10%) Ground-Glass Opacity Component in Clinical Stage I Non-Small Cell Lung Cancer: Associations With Pathologic Characteristics and Clinical Outcomes.

BACKGROUND. The presence of a ground-glass opacity (GGO) component is a favorable prognostic factor in non-small cell lung cancer (NSCLC), although the prognostic impact of a very small GGO component remains poorly investigated. OBJECTIVE. The purpose of this article is to investigate the impact of a minor (≤ 10%) GGO component on the prognosis of clinical stage I NSCLC in comparison with pure-solid nodules. METHODS. This retrospective study included 382 patients (mean age, 60.8 years; 210 men, 172 women) who underwent surgical resection between January 1, 2015, and December 31, 2015, for clinical stage I NSCLC appearing on preoperative chest CT as a nodule with a consolidation-to-tumor ratio (CTR) of 0.9 to 1.0. Two radiologists independently assigned nodules to groups as either minor GGO (CTR, ≥ 0.9 and < 1.0) or pure solid (CTR = 1.0). Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed by Kaplan-Meier curves and compared between groups using log-rank tests. Cox proportional hazards models were used to assess associations with outcomes. RESULTS. The two radiologists agreed for all nodules' classification into the minor-GGO (n = 106) or pure-solid (n = 276) groups. The mean CTR of the minor-GGO group was 0.93 ± 0.02 (SD) (range, 0.90-0.97). Minor-GGO nodules, in comparison with pure-solid nodules, showed greater solid-component diameter (2.68 vs 2.16 cm; p < .001) and total nodule diameter (2.89 vs 2.16 cm; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed lower frequencies of visceral pleural invasion (6.6% vs 17.0%, p = .009) and pathologic lymph node involvement (4.7% vs 20.3%, p < .001), and EGFR mutation (71.6% vs 39.9%; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed better 5-year RFS (83.4% vs 55.0%; p < .001) and higher frequency of better 5-year CSS (92.4% vs 76.4%, p = .004). In multivariable analysis adjusting for patient, imaging, pathologic, and genetic factors, a minor-GGO component was independently associated with a decreased likelihood of recurrence (HR = 0.37, p = .001) but not with the likelihood of CSS. CONCLUSION. Among patients with clinical stage I NSCLC, cancers with a minor-GGO component were associated with a better prognosis versus those with a pure-solid appearance. CLINICAL IMPACT. Radiologists encountering predominantly solid nodules on CT should carefully assess images for even a minor-GGO component given the favorable prognosis.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer.

Colorectal cancer (CRC) is a prevalent global malignancy with complex prognostic factors. Tumor-associated macrophages (TAMs) have shown paradoxical associations with CRC survival, particularly concerning the M2 subset. We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors. A cross-sectional study included histopathological assessment of paraffin-embedded tissue blocks obtained from 43 CRC patients. Using CD68 and CD163 immunohistochemistry, we quantified TAMs in tumor stroma and front, focusing on M2 proportion. Demographic, histopathological, and clinical parameters were collected. TAM density was significantly higher at the tumor front, with the M2 proportion three times greater in both zones. The tumor front had a higher M2 proportion, which correlated significantly with advanced tumor stage (P = 0.04), pathological nodal involvement (P = 0.04), and lymphovascular invasion (LVI, P = 0.01). However, no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors. Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples. We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage, nodal involvement, and LVI. This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC, warranting further investigation and potential clinical application.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. Five hundred and ninety patients were included, with a median follow-up of 28months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Abstract 5047: Identifying genomic features associated with pathologic lymph node metastasis in lung adenocarcinoma patients

Abstract Introduction: Lymph node metastasis evaluation in solid tumors is mainly complicated by the diagnostic yield of standard imaging modalities and tumor size contradictions. Exploring clinical/molecular features that complement the use of radiologic and bronchoscopy findings may provide significant values for a more accurate pathologic determination of nodal metastasis. Methods: We analyzed surgery-resected tumor samples from 72 treatment-naïve lung adenocarcinoma (LUAD) patients via whole-exome sequencing (WES). Mutational profiles of patients categorized based on their pathologic lymph node metastasis (pN) status were assessed, and the association between metastatic-driving features and overall survival (OS) was then explored in both the study cohort and the Cancer Genome Atlas Program (TCGA) external cohort. Results: Among all 72 patients, 41 (56.9%) were pathologically confirmed as positive for lymph node metastasis (pN-positive), while 31 (43.1%) were categorized as pN-negative. The most frequently mutated gene was TP53 in both subgroups (54.8% and 53.7%, respectively), and the aberrant KEAP1-NRF2 signaling pathway was found significantly more enriched in pN-negative patients. Copy-number variant analysis showed that chromosome 7p amplifications (X7p_amp) at the arm level and EGFR amplifications at the focal gene level were more frequently identified in pN-positive patients (P=0.008 and P=0.004, respectively). Importantly, these amplifications were associated with worse OS in both the study cohort and the TCGA external dataset. Consistent with the unfavorable prognosis, pN-positive patients demonstrated a higher chromosome instability score (CIS) (median: 0.32 vs. 0.14, P=0.14) and a lower tumor mutation burden (TMB) (median: 1.83 vs. 3.85 muts/Mb, P=0.048) compared to pN-negative patients. Conclusion: Our findings suggest that X7p_amp, particularly EGFR amplification, might be associated with pathologic involvement of lymph nodes and an unfavorable prognosis in LUAD patients. Our study highlights the importance of integrating clinical and genomic data into conventional radiologic modalities for a more accurate determination of pathologic nodal involvement. Citation Format: Shijie Wang, Zhiwei Zhou, Song Wang, Rongyun Guo, Zeming Ma, Dachuan Zhao, Liang Wang, Yinan Liu, Yuanyuan Ma, Jianzhi Zhang, Sha Wang, Yedan Chen, Haimeng Tang, Qiuxiang Ou, Jinfeng Chen. Identifying genomic features associated with pathologic lymph node metastasis in lung adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5047.

Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.

The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59years (range, 27-90years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50years had a 47.1% likelihood of pN+ disease. Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.

Utility of fluoro-deoxy-glucose positron emission tomography (FDG-PET) to predict a pelvic lymph node involvement (LNI) in patients (pts) with muscle-invasive bladder cancer (MIBC) enrolled in neoadjuvant therapy trials.

527 Background: FDG-PET is reported to have limited utility in pts with MIBC. However, standard computed tomography (CT) imaging can often underestimate disease extent, and its role in predicting a pathological pelvic lymph node involvement (LNI) is very limited. Previous findings from PURE-01 trial reported a potential use of FDG-PET to exclude the few pts with T2-4N0M0 and pelvic LN uptake from neoadjuvant trials with immune-checkpoint inhibitors (ICI; PMID: 33071107). The aim of this study was to extend these findings to a wider range of experimental therapies. Methods: We collected the data of pts with clinical stage T2-4N0-1M0 MIBC included in past and ongoing neoadjuvant trials sponsored by our center, including single agent or combination of immune-checkpoint inhibitors (ICI), ICI+chemotherapy (ChT), standard ChT and sacituzumab govitecan. All pts had predominant urothelial carcinoma (UC) histology and were staged with standard thorax-abdomen CT scan and with PET/CT scan during screening and after treatment, before radical cystectomy (RC). PET/CT images were evaluated qualitatively for increased or abnormal areas of FDG uptake with corresponding anatomic alterations in CT slices. All pts underwent templated pelvic lymph node dissection (LND) with packeted node submission. Multivariable logistic regression analyses (MVA) for pathological LNI prediction were run, including cT-stage and the presence of variant histologies (VH). Results: A total of 149 pts (298 PET scans) were identified, treated between 02/2017 and 08/2023. 112 pts (75.2%) received ICI, 26 (17.4%) ICI+ChT, 11 (7.4%) the remaining therapies. 36 pts (24%) had a VH, 72 (48%) a cT3-4 stage, and 12 (8.1%) a cN1 stage. In total, 20 (13%) and 16 (11%) pts had PET+ pre- and post-therapy, respectively. The accuracy of FDG-PET and CT scan in predicting LNI in overall pts was similar, both pre-therapy (85.3% and 86.7%) and post therapy (86.7%, 84.6%), the only exceptions being a lower accuracy of PET to predict presacral LNI (76.6%, 78.8% pre- and post-therapy) and in VH pre-therapy (84.3% vs 90.9% PET vs CT). A pre-therapy FDG uptake significantly predicted a pathological LNI in MVA (OR: 17.8, 95%CI: 4.18-94.86, p&lt;0.001, AUC: 0.89), with consistent results in T2-4N0M0 cohort (OR: 18.17, 95%CI: 4.15-99.25, p&lt;0.001, AUC: 0.84). Conclusions: Despite the proportion of FDG-PET positive pts was modest in T2-4N0-1M0 MIBC, we were able to confirm that these pts were predicted to be poor responders to neoadjuvant therapies regardless of the type of treatment. FDG-PET had lower prediction ability of LNI in presacral LN region and in pts with a VH. This information should be critically considered for patient selection in neoadjuvant therapy trials.

Prognostic thresholds of fluorine-18 fluorodeoxyglucose-positron emission tomography mean and maximum standardized uptake values for survival and nodal involvement in lung neuroendocrine neoplasms.

The mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose-positron emission tomography are prognostic biomarkers for survival and nodal involvement in non-small-cell lung cancer but their prognostic value in lung neuroendocrine neoplasms (NENs) remains unexplored. In this study, we aimed to examine whether they are also prognostic biomarkers for survival and nodal involvement in lung NENs. We retrospectively studied patients with typical carcinoid, atypical carcinoid or large cell neuroendocrine carcinoma who had been radically resected at our institution between 2008 and 2020. We measured SUVmean and SUVmax on all primary tumours and lymph nodes that were clinically and/or pathologically involved. We dichotomized the patients into groups of high or low SUVmean and SUVmax of the primary tumour using time-dependent receiver operating characteristic curves and compared their overall survival using Kaplan-Meier curves and Cox models. Lastly, we predicted the patients' pathological nodal status with SUVmean and SUVmax of the lymph nodes using binomial logistic models. The study included 245 patients. Patients died earlier if their SUVmean of the primary tumour exceeded 3.9 [hazard ratio 1.97, 95% confidence interval (CI) 1.27-3.04, P = 0.002] or SUVmax exceeded 5.3 (hazard ratio 1.85, 95% CI 1.20-2.87, P = 0.006). Likewise, patients had a higher risk of pathological nodal involvement if their SUVmean of the lymph nodes exceeded 3.3 (odds ratio 10.00, 95% CI 2.59-51.01, P = 0.002) or SUVmax exceeded 4.2 (odds ratio 4.00, 95% CI 1.20-14.65, P = 0.028). The fluorine-18 fluorodeoxyglucose-positron emission tomography SUVmean and SUVmax are strong prognostic biomarkers for survival and nodal involvement in lung NENs and could be important guides for making treatment decisions.

Neoadjuvant SBRT plus regional nodal irradiation with concurrent capecitabine for patients with resectable pancreatic cancer: Survival analysis of prospective phase 1 trial.

652 Background: Radiation may have a role in management of patients with early-stage pancreatic cancer. However, the role of regional nodal irradiation (RNI) is not well defined despite the high frequency of occult nodal disease. The goal of this trial was to evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) to primary disease with RNI, combined with capecitabine as a neoadjuvant approach for patients with resectable pancreatic cancer. Updated survival analysis will be presented here. Methods: This is a prospective, single institution, phase IA/B dose-escalation trial that enrolled patients with biopsy-proven, resectable, pancreatic adenocarcinoma between 2014 – 2019 (NCT1918644). Patients were enrolled into one of the 3 cohorts with escalating dose levels. Neoadjuvant SBRT to the primary tumor was delivered in 5 fractions of 5, 6, or 7 Gy with concomitant capecitabine. All patients received RNI 5 Gy x 5 fractions. Our initial report found no dose-limiting toxicities (Witt et al IJROBP 2020). Clinicopathologic features were summarized using descriptive statistics. Kaplan-Meier curves were employed for survival analysis. Results: Seventeen patients were enrolled on the protocol with sixteen evaluable (94.1%). Thirteen (76.5%) patients proceeded to surgery. Median follow up was 31.1 months (2.0 – 73.2). Among the evaluable patients, 63% were male, median age at diagnosis was 73 years (63 – 84), pre-treatment CA 19-9 149.5 U/mL (2.0 – 19358.0). The majority of patients had cT2-3 (94%) and cN0 (87.5%) disease. In patients who underwent resection, median time from radiation to surgery was 19.7 days (14.8 – 42.4), with median of 18 lymph nodes removed (11 – 27). Pathologically involved nodes were present in 69.2% of patients with a median of 2 nodes (1 – 10). Five patients (31.3%) received neoadjuvant chemotherapy, and ten (62.5%) received adjuvant chemotherapy. At the time of data cutoff, median overall survival was 31.1 months (2.3 – 73.6), and median locoregional control and distant metastasis free survivals were 32.8 months (4.0 – 59.5) and 15.3 months (0.4 – 73.6), respectively. No further radiation related toxicities were noted since the prior report. Conclusions: Neoadjuvant chemoradiation with SBRT and capecitabine to primary disease with RNI is feasible and provided a promising signal of durable local control in our study, despite high rates of pathological nodal involvement. Further investigation of this strategy is warranted in a larger cohort of patients. Clinical trial information: NCT1918644 .

Additional Parameters to the Briganti Nomogram for Predicting Pelvic Lymph Node Metastasis in Prostate Cancer.

Despite advanced medical technology, accurately predicting pelvic lymph node (LN) metastasis in patients with prostate cancer (PCa) remains a challenge. Various nomograms were utilised to enhance the accuracy of this prediction. Our goal was to determine if preoperative inflammation markers and transrectal prostate biopsy data offer extra insight into predicting pathological LN involvement in radical prostatectomy with extended pelvic LN dissection (RP + ePLND). This study included patients with PCa who had a Briganti score of 5 or higher and were treated with RP + ePLND between January 2016 and May 2023. Physical examination findings, blood work within 1 month before biopsy and prostate biopsy results were recorded retrospectively. The patients were divided into two groups based on the presence or absence of pelvic LN metastasis (group 1 and group 2, respectively). The preoperative data of both groups were compared for analysis. The study involved 71 patients; 17 were in group 1, and 54 were in group 2. We observed significant differences between the groups in terms of bilateral tumour involvement in prostate, presence of perineural and lymphovascular invasion (LVI) in biopsy specimens, D'Amico risk group, as well as haematological and biochemical parameters such as the absolute counts of lymphocyte and monocyte, neutrophil-to-lymphocyte ratio and the levels of total and free prostate-specific antigen. Logistic regression analysis revealed that absolute lymphocyte count, presence of LVI and bilateral tumour involvement were independent predictors of pathological pelvic LN metastasis in PCa. The cut-off value of lymphocyte count for predicting LN metastasis was 1.57 (103/mL) with a sensitivity of 0.870 and a specificity of 0.412 (area under the curve (AUC): 0.675, p = 0.030). According to our findings, LVI in biopsy specimens, bilateral lobe tumours and preoperative lymphocyte count are significant predictors of pelvic LN metastasis in patients with PCa and a Briganti score of ≥5.

Comparison of aggressiveness in central versus peripheral T1a clear-cell renal cell carcinoma

PurposeThis study aimed to estimate the difference between peripheral and central small renal lesions in terms of their oncologic potential. MethodsCross-sectional retrospective analysis of patients with small renal masses (T1a) who underwent surgical treatment between January 2008 and July 2019 at the affiliated hospital. Only patients with ccRCC pathology were included. Cases were divided into 2 groups depending on tumor location (central or peripheral) based on the R.E.N.A.L and local nephrometry scoring. Presence of nodal involvement, distant metastases, ISUP grade and endophytic growth were defined as aggressiveness predictors. Statistical analyses was performed using a standard statistical software (IBM SPPS Statistics Ver. 22), with P < 0.05 considered statistically significant. Associations between tumor location and Fuhrman grade, exo-/endophytic growth, TNM classification, and type of operation were tested using the Pearson χ² test and 1-way ANOVA test. ResultsPatients with centrally located tumors had a higher incidence of clinical and pathological lymph node involvement (P = 0.02, χ2 = 5.1). Patients in both groups had an equal number of distant metastases at the time of diagnosis (P = 0.3, χ2 = 0.8). The operation time was significantly longer in patients with central lesions, which obviously showed higher tumor complexity in this group (P < 0.005). Pathological evaluation revealed differences between ISUP grades in both groups (P < 0.005, χ2 = 29.9). Central masses were characterized by higher aggressiveness, indicating a worse prognosis. Furthermore, the cases in the first group were more often endophytic (P = 0.03, χ2 = 0.9). Nevertheless, this did not affect the surgical strategy in most cases with a tendency toward partial nephrectomy. Eventually, organ-sparing treatment was preferable in both groups (P = 0.13, χ2 = 2.29). ConclusionCentrally located kidney cancer has showed in present study a higher incidence of high ISUP grade, regional nodal involvement and endophytic growth type. Endophytic growth type was associated with worse ISUP grading. Distribution of ISUP grade was not age depended, thus showing no difference by this criterion, when comparing different age groups. Higher ISUP grade was strongly associated with presence of distant metastases in T1a kidney tumors. Further analysis is needed to investigate aggressiveness of centrally located T1a RCC, as it may influence current conservative management options.

Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma

Introduction: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15–20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. Methods: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. Results: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14–12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. Conclusions: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC.

Net survival in colon and rectal cancer by stage according to neoadjuvant treatment. A French population-based study

AimReal-life estimations of survival by stage in colorectal cancer are scanty. We estimated population-based net survival by pathological stage and location, and for rectal cancer by patterns of evolution according to clinical and pathological stage with regard to neoadjuvant therapy. MethodAge-standardized net survival was estimated on 19,630 colorectal cancers diagnosed between 2009 and 2015. ResultsFive-year net survival was 64 % for colon and 62 % for rectal cancer. The highest absolute difference between colon and rectum was 12 % for stage II women aged 75 (91% vs. 79 %). Among patients with clinical stage III rectal cancer, 67 % no longer had pathological node involvement after neoadjuvant treatment. Survival was similar in clinical stage I, II or III and pathological stage III after neoadjuvant treatment and in pathological stage III without neoadjuvant treatment (between 67 % and 72 %). It ranged between 80 and 82 % in pathological stage II, without neoadjuvant treatment or with clinical stage I, II or III before neoadjuvant treatment. Survival ranged between 93 % and 95 % in pathological stage I, treated with surgery only or with clinical stage II or III before neoadjuvant treatment. ConclusionPrognosis is associated with stage determined on surgical specimens rather than stage at the initial workup.

Spectrum of malignant scalp tumours and its impact on management—a tertiary care cancer centre experience

BackgroundTumours on the scalp are diverse and often exhibit site- and histology-specific characteristics. Reconstructing the scalp after oncological resection has always been challenging because of its unique anatomy.MethodologyA retrospective review of patients with malignant scalp tumour operated on at a single institution over 10 years was performed. Data were collected and analysed regarding the scalp tumour profile, treatment, and the outcome of these procedures.ResultsOf the 66 patients in our study, 33 (50%) had SCC. In addition to this, 21% were sarcomas, 17% were appendageal carcinomas, 11% were BCCs, and 1% was neuroendocrine carcinoma. Cortical erosion was observed in 6 patients in the CT imaging, all with SCC histology. Among the eight patients with pathological nodal involvement, three had angiosarcoma, three had SCC, one had appendageal carcinoma, and one had neuroendocrine carcinoma. The mean surgical defect size was 67.4 cm2. The surgical defect was reconstructed with local flaps in 58% of patients and primary closure in 27%. Local and systemic recurrence was noted in 25% of patients. Tumour size more than 6 cm, tumour histology (SCC & sarcoma), unplanned margin-positive excision, and residual disease in re-excision had higher recurrence, even though the p-value was not significant.ConclusionScalp tumours are heterogeneous in their clinical profiles. Often, its tumour biology and microscopic extent are underestimated. High suspicion, histological diagnosis, and clear surgical margins are all requirements in successfully treating scalp tumours. In order to minimize morbidity and restore an aesthetic and functional outcome, it is critical to use the simplest scalp reconstruction whenever possible.

Patterns of Recurrence Following Radiation and ADT for Pathologic Lymph Node Positive Prostate Cancer: A Multi-Institutional Study

Retrospective studies have suggested that post-operative radiation therapy (RT) can reduce the risk of cause-specific mortality in men with pathologic nodal involvement (pN1) after radical prostatectomy (RP). We evaluated prognostic factors and patterns of recurrence in patients who received post-operative RT +/- androgen deprivation therapy (ADT) for pN1 disease in a multicentric cohort of 4 academic centers. Data from patients with pN1 prostate cancer after RP who subsequently received RT with short term (< = 6 mo) or long term (>6 mo) ADT were obtained from 4 academic institutions. Patterns of recurrence, biochemical progression free survival (bPFS) and distant metastasis free survival (DMFS) were evaluated. A total of 270 patients with a median follow-up of 48 months were included. Gleason grade group (GG) 2 was present in 20 patients (7.5%), GG 3 in 81 (30%), GG4 in 36 (13.5%), GG5 in 130 (49%) patients. 256 (95%) patients had extracapsular extension, 70% had seminal vesicle invasion, 59% had positive surgical margins, and 66% had a detectable post-operative PSA. The number of positive nodes at surgery were 1 in 59%, 2 in 19% and >2 in 22% of patients. Of the 83 patients that had pre-RT imaging, 46 (55%) had a PET scan (PSMA, or fluciclovine); 25 (30%) of those had lymph nodes detected on imaging prior to RT. Median time from RP to RT was 6 mo (IQR 4.5-9.1 mo). 96% received radiation to both the prostate bed (median dose 68.4Gy) and pelvic lymph nodes (median dose 46Gy). ADT was prescribed short-term (20%) or long-term (68%), while 26 (10%) received no ADT, and 7 (3%) had an unknown duration. Biochemical failure (bF) was observed in 29% of men, with 5% having pelvic nodal failure and 11.5% having distant metastases (majority in bones, followed by paraaortic nodes) at last follow up. Of 59 patients who had normal baseline testosterone levels, 37% recovered their testosterone by last follow-up. The 4-year bRFS was 72% for all patients and was 83% for those with a pre-RT PSA of <0.1 ng/mL, 76% for PSA 0.1-<0.5 ng/mL, 60% for PSA 0.5-2 ng/mL, and 35% for PSA >2 ng/mL. On multivariable analysis, maximum pre-RT PSA ≥0.5 (0.5 to 2.0 vs <0.1 HR = 3.19; >2.0 vs <0.1 HR = 9.00), use of LTADT (HR = 0.47), and percent pN1 (HR = 1.03) were significantly associated with bF. Pre-RT PSA >2 (HR = 4.10), use of LT ADT (HR = 0.33) and percent pN1 (HR = 1.03) were also significantly associated with DM. In pN1 patients, pelvic RT and ADT at low PSA levels is associated with improved oncologic outcomes compared to treatment at higher levels, suggesting that PSA may have prognostic value for pN1 prostate cancer.

Long-term oncologic and functional outcomes following robot-assisted radical cystectomy and intracorporeal Padua ileal bladder: results from a single high-volume center.

To report long-term oncologic and functional outcomes of a large consecutive single center series of Robot-assisted radical cystectomy (RARC)- intracorporeal (IC) Urinary Diversion (UD), identifying their predicting factors. A single center Bladder cancer (BC) database was queried for "RARC" and "ICUD", including patients treated between January 2012 and September 2020. Kaplan-Meier curves were assessed disease-free (DFS), cancer-specific (CSS) and overall survival (OS) probability. Univariable (UV) and multivariable (MV) analysis were adopted to identify predictors of DFS, CSS and OS. Kaplan-Meier method evaluated day- and night-time continence recovery probabilities; UV and MV analysis were adopted to identify predictors of Day-time continence. Overall, 251 patients were included. Among them, 192 patients underwent intracorporeal ileal orthotopic neobladder (ION) (76.5%). Five-year DFS, CSS and OS rates were 66.5%, 65.4% and 61.5%; pT stage ≥ 3 and pathologic nodal involvement were identified as negative independent predictors of DFS (HR 2.39, p = 0.001, HR 4.64, p ≤ 0.001), CSS (HR 2.20, p = 0.01, HR 3.97, p < 0.001) and OS (HR 2.25, p = 0.005, HR 3.95, p < 0.001). In RARC-ION patients, Trifecta rate was 64.1%. One-year day- and night-time continence rates were 78.6% and 48.3%. Age (HR 0.98, p = 0.03), female gender (HR 0.57, p = 0.008) and complications Clavien grade ≥ 3 (HR 0.55, p = 0.03) were identified as independent predictors of day-time incontinence. Long-term oncologic outcomes and their predicting factors seem aligned to the largest historical open series and multi-institutional robotic series data. According to the identified predicting factors undermining a proper achievement of day-time continence, this represents an objective support, in order to properly advice specific sub-group of patients.