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Purpose: To investigate the clinical significance and stage migration effect of radiological diameter-to-thickness (DT) ratio in HER2-positive resectable advanced gastric cancer (HER2-p RAGC). Methods: 369 HER2-p RAGC patients were retrospectively enrolled and information on clinical pathological characteristics, radiological DT ratio, and outcomes [i.e., overall survival (OS) and progression-free survival (PFS)] was collected. Pearson's Chi-square and Student's t-test were employed to compare baseline characteristics. Clinical outcomes were estimated using Kaplan–Meier analysis and Log-rank test. Univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors. Results: HER2-p RAGC patients were stratified into two groups using a DT ratio cutoff value of 4.0 (p < 0.05). Patients with a DT ratio < 4.0 exhibited significantly longer OS (58.0 vs. 31.0 months) and PFS (43.0 vs. 24.0 months) than those with a DT ratio ≥ 4.0. DT ratio significantly predicted prognosis for N0 and II stage patients (p < 0.05). Patients with gastric body and antrum cancers demonstrated longer OS and PFS in the DT ratio < 4.0 group (p = 0.046, 0.017, 0.036 and 0.028). Multivariate Cox proportional hazard model identified age, pathological T category, pathological N category, pathological TNM category and DT ratio as independent prognostic factors. Notably, pStage II patients with a DT ratio ≥ 4.0 exhibited a similar prognosis to pStage III patients with a DT ratio < 4.0 (p = 0.418 for OS, 0.867 for PFS). Conclusion: Radiological DT ratio could evaluate the prognosis and detect higher malignant cases in HER2-p RAGC patients. Moreover, DT ratio might guide clinicians make postoperative strategies. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: To summarize stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system, and to investigate prognostic factors influencing Stage IIIC1. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to February 6, 2024. The analysis was conducted using STATA 16.0. Results: A total of 25 studies with 82954 cervical cancer patients were included in the analysis. The migration rates to FIGO 2018 Stage IIIC ranged from 18% to 37% for early-stage tumors (Stage IB to IIA) in FIGO 2009, and from 32% to 52% for advanced stage tumors (Stage IIB to IIIB). The overall survival (OS) for Stage IIIC1 is poorer compared to Stage IB1 (HR 0.53, 95% CI 0.35-0.80, p=0.003) and Stage IB2 (HR 0.61, 95% CI 0.43-0.85, p=0.004). It is comparable to Stage IB3, yet it shows better survival outcomes than Stages IIB (HR 2.91, 95% CI 1.01-8.39, p=0.047), IIIA (HR 1.96, 95% CI 1.78-2.17, p=0.000), and IIIB (HR 1.56, 95% CI 1.04-2.35, p=0.031). Tumors size =4cm (HR 1.45, 95% CI 1.10-1.92, p=0.00), metastatic lymph node = 3 (HR 2.21, 95% CI 1.56-3.15, p=0.000) and T stage are prognostic factors for OS of Stage IIIC1. Conclusions: The migration rates to FIGO 2018 Stage IIIC varied between 18% and 52% for patients initially classified under FIGO 2009 Stages IB1 to IIIB. The FIGO 2018 staging system underscores the pivotal role of lymph node metastasis in predicting prognosis and provides valuable insights into the distinct prognostic implications associated with different stages, particularly for early stages. For advanced stages, incorporation of tumor-related factors such as T stage might better elucidate survival differences and guide clinical treatment decisions. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of the present study was to determine the role of changes in the stage of colorectal cancer (CRC, Stage 0 to 4, with 0 be very early stage and 4 late stage) at diagnosis over time, and its impact on overall survival (OS) in our Health Network system. Two datasets were used, the Health Network (n = 1385) and a national dataset (n = 202,391). There was a significant increase in early CRC stages at diagnosis (Stage 0–1), and late diagnosis (Stage 4) with a concomitant decrease in the diagnosis of CRC Stage 2. The present findings confirmed CRC stage migration in our Health Network System, along with a national trend conducive to an increased OS for early CRC stages. Background/Objectives: Due to an increased rate of surveillance colonoscopy, we aim to determine the impact of stage migration on the incidence and overall survival (OS) of patients who underwent pathological staging of colorectal cancer (CRC) at our Health Network System. Methods: Two datasets were included: subjects from the tumor registry at a regional Comprehensive Cancer Center (n = 1385) and subjects from the Surveillance, Epidemiology, and End Results (SEER) national database (n = 202,391). Results: A significant increase in the diagnosis of CRC Stage 1 and 4 was observed, with a decrease in stage 2, and no change in Stage 3 in the National datasets (p < 0.01). There was an increase in Stage 4 CRC diagnosis, with a concurrent decrease in stage 2, and no changes in stages 1 and 3 in the regional dataset (p < 0.05). OS followed the expected and progressive decrease in OS by stage (from 1 to 4, p < 0.01). Conclusions: The present findings confirmed CRC stage migration in our Health Network System, along with a national trend conducive to an increased OS for early CRC stages. [ABSTRACT FROM AUTHOR]

Background: The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility. Methods: Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria. Results: The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented. Conclusion: Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community. [ABSTRACT FROM AUTHOR]

Background/Aim: Stage migration, a phenomenon triggered by technological advancements allowing more sensitive tumor spread detection, results in alterations in the distribution of cancer stages within a population. Canine multicentric lymphoma is staged I to V based on the affected anatomic site(s) and substage a or b depending on the presence of tumor-related clinical signs. The primary objective of this study was to assess the influence of various diagnostic techniques on staging accuracy and determine whether multiple staging methods lead to significant stage migration, impacting the reliability of disease stage assignments. Materials and Methods: Dogs cytologically diagnosed with multicentric lymphoma were staged using four different staging methods (A-D): A (physical examination, hemogram, blood smear), B (A plus thoracic X-ray, abdominal ultrasound), C (B plus liver and spleen cytology) and D (C plus bone marrow cytology). Results: Twenty-three dogs were enrolled: 16 females (70%) and seven males (30%). Regarding immunophenotype, 21 dogs (91.3%) were B-cell and two dogs (8.7%) were T-cell. Stage migration was observed between all staging methods. Between A and B, 12 animals migrated from stage III to stage IV. Between B and C, four animals migrated, three to a higher stage (stage III to IV) and one to a lower stage (stage IV to III). Between C and D, one animal migrated from stage IV to V. The differences between staging methods A and B were statistically significant (p≤0.001). Conclusion: Stage migration in canine multicentric lymphoma depends on the diagnostic methods used and reinforces the need to use standardized staging methods to avoid it. [ABSTRACT FROM AUTHOR]

Purpose: Phase III evidence showed that next-generation imaging (NGI), such as prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), provides higher diagnostic accuracy than bone scan and contrast-enhanced computed tomography (conventional imaging, CI) in the primary staging of intermediate-to-high-risk prostate cancer (PCa) patients. However, due to the lack of outcome data, the introduction of NGI in routine clinical practice is still debated. Analysing the oncological outcome of patients upstaged by NGI (though managed according to CI) might shed light on this issue, supporting the design of randomised trials comparing the effects of treatments delivered based on NGI vs. CI. Methods: We prospectively enrolled a cohort of 100 biopsy-proven intermediate-to-high-risk PCa patients staged with CI and PSMA PET/CT (though managed according to the CI stage), to assess the frequency of the stage migration phenomenon. Stage migration was then assessed as biochemical recurrence—free survival (bRFS) predictor. Results: Three patients were lost at follow-up after imaging. PSMA PET/CT upstaged 26.8% of patients compared to CI, while it downstaged 6.1% of patients. Notably, 50% of patients excluded from surgery due to the presence of bone metastases at CI would have been treated with radical-intent approaches if PSMA PET/CT had guided the treatment choice. After a median follow-up of 6 months of surgically treated patients, 22/83 (26.5%) had biochemical recurrence (BCR). PSMA PET/CT-driven upstaging determined a significant risk increase for BCR (HR:3.41, 95%CI:1.21–9.56, p = 0.019). Including stage migration in a univariable and multivariable model identified PSMA PET/CT-upstaging as an independent predictor of bRFS. Conclusions: In conclusion, implementing NGI for staging purposes improves the prediction of bRFS. Although phase III evidence is still needed, this advancement suggests that NGI may better identify patients who would benefit from local treatments than those who may achieve better oncological outcomes through systemic treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Merkel cell carcinoma (MCC) is a rare, aggressive type of skin cancer that has been found to respond well to immunotherapy in the metastatic setting; ongoing large trials are exploring the addition of this therapy to earlier stage disease to prevent recurrence after surgery, particularly distant metastatic recurrence. However, newer clinical data suggest that non-metastatic MCC may have a better prognosis than what was previously observed, in part because of new technologies that have improved the detection of MCC spread to regional lymph nodes or other organs (i.e., distant metastases). Thus, preventing MCC from recurring in the area of the original surgery may be more important in achieving a cure for these patients without distant metastatic disease. Radiation therapy is an effective treatment for preventing these local recurrences, but there is significant variability in how ongoing immunotherapy trials allow for its use. This review describes the evidence supporting the ongoing use of adjuvant radiation therapy, how variability in radiation therapy use may have led to negative results in a large trial of immunotherapy in non-metastatic MCC, and the risk this poses for two large ongoing studies in this domain. Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and often fatal. This has prompted new efforts to intensify treatment in these patients with the addition of neoadjuvant or adjuvant immune checkpoint inhibitor therapy. However, newer diagnostic techniques have led to stage migration in patients with previously subclinical metastatic disease; consequently, preventing locoregional recurrence may be a higher priority in node-positive MCC patients than was previously believed. Recent trials in node-positive MCC, such as ADMEC-O, have had lower rates of adjuvant RT utilization in treatment versus control arms, which may have attenuated the observed effect of adjuvant immunotherapy. The low utilization of adjuvant RT may have also resulted in a higher recurrence rate in patients who did not have a complete response to neoadjuvant immunotherapy in the CHECKMATE 358 trial. Altogether, these are important considerations for ongoing and future immunotherapy trials in MCC and may affect the interpretation of their results. Ongoing clinical trials may determine which patients are at low risk of recurrence when treated with immunotherapy and whether adjuvant RT could be omitted in select patients. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency of occult metastases (OM) in patients with resected pancreatic ductal adenocarcinoma (PDAC) or ampullary adenocarcinoma (AA) discovered on detailed pathologic examination on lymph nodes (LNs) previously considered negative by conventional analysis and to examine the association between OM and overall survival (OS). Background: Poor prognosis of patients with no pathologic evidence of LN metastases may be due to OM that is not detected on conventional LN analysis. Methods: Patients with LN-negative resected PDAC or AA (2010--2020) were identified from our institutional database. Original hematoxylin and eosin (H and E) slides were reanalyzed. In addition, selected LN were analyzed by H and E (3 sections/LN) and pan-cytokeratin (AE1-AE3/ PCK26) immunohistochemistry. Results: A total of 598 LNs from74 LN-negative patients were reexamined. Nineteen patients (25.7%) had OM; 9 (47.4%) were found with immunohistochemistry but not on H and E. The number of positive LNs ranged from 1 to 3. No clinicodemographic, pathologic, or treatment-related factors were associated with OM. On conventional LN analysis, 3/19 patients (15.8%) had stage IA, 9/34 (26.5%) had stage IB, and 7/19 (36.8%) had stage IIA. On detailed LN analysis, 11/19 patients (57.9%) were upstaged to IIB, whereas 8/19 (42.1%) had isolated tumor cells only (N0i+). OM was associated with shorter OS (median OS: 22.3 vs 50.5 months; hazard ratio=3.95, 95% CI: 1.58--9.86). Conclusions: There is a 26% discordance rate between conventional and detailed LN pathologic analysis in resected PDAC and AA. The presence of OM is associated with shorter OS. [ABSTRACT FROM AUTHOR]

Introduction: In early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC). Methods: From the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN = 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method. Results: More ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range. Discussion: Neither too many nor too few numbers of ELN were ideal for earlystage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy. [ABSTRACT FROM AUTHOR]

Several clinical trials have been revolutionizing the perioperative treatment of early-stage non-small cell lung cancer (NSCLC). Many of these clinical trials involve cancer immunotherapies with antibody drugs that block the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand PD-L1. While these new treatments are expected to improve the treatment outcome of NSCLC patients after pulmonary resection, several major clinical questions remain, including the appropriate timing of immunotherapy (neoadjuvant, adjuvant, or both) and the identification of patients who should be treated with neoadjuvant and/or adjuvant immunotherapies, because some early-stage NSCLC patients are cured by surgical resection alone. In addition, immunotherapy may induce immune-related adverse events that will require permanent treatment in some patients. Based on this fact as well, it is desirable to select appropriate patients for neoadjuvant/adjuvant immunotherapies. So far, data from several important trials have been published, with findings demonstrating the efficacy of adjuvant atezolizumab (IMpower010 trial), neoadjuvant nivolumab plus platinum-doublet chemotherapy (CheckMate816 trial), and several perioperative (neoadjuvant plus adjuvant) immunotherapies (AEGEAN, KEYNOTE-671, NADIM II, and Neotorch trials). In addition to these key trials, numerous clinical trials have reported a wealth of data, although most of the above clinical questions have not been completely answered yet. Because there are so many ongoing clinical trials in this field, a comprehensive understanding of the results and/or contents of these trials is necessary to explore answers to the clinical questions above as well as to plan a new clinical trial. In this review, we comprehensively summarize the recent data obtained from clinical trials addressing such questions. [ABSTRACT FROM AUTHOR]

Background: Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC. Methods: Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I--III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS). Results: The distribution of ELN count between the Chinese registry (n =7694) and SEER database (n= 21 332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P< 0.001; Chinese registry, OR, 1.016, P= 0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P< 0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival. Conclusions: A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis. [ABSTRACT FROM AUTHOR]

• No significant increase or decrease in cancer cervix cases was noted during the pandemic period. • Referral routes were also unchanged. • Statistically significant stage migration from FIGO stage 2 to stage 3 was noted in pandemic period cases. • More research is required to see if the findings are noted on wider population base. Concerns were raised by clinicians at the Oxford Gynaecological Cancer MDT that there was an increasing number of women presenting with large cervical tumours requiring chemo-radiotherapy, possibly due to delays associated with the COVID pandemic. This audit was undertaken to assess whether this was a real event. This retrospective cohort study collated the data from the central pathology service covering Oxfordshire, in the Oxford Gynaecological cancer centre. The control population consisted of patients treated during the 2 years pre-pandemic (1st Jan 2018–31 Dec 2019) and the study group the 2-year pandemic period (1st Jan 2020 until 31st December 2021). A total of 153 patients (74 control and 79 study) were diagnosed of cervical cancer during the study period. Variables included in the analysis were age, pathway of referral and diagnosis (cytology or clinical), FIGO stage, tumour histology, tumour size (using maximum diameter on MRI) and treatment. Student's t -test was used for continuous and discrete variables, respectively. The X2 test was used for the statistical analysis of proportions. There was no statistically significant differences was noted in the referral pathways during both periods. Statistically significant stage migration from FIGO stage II to III was detected (p < 0.05), though no statistically significant change in tumour size. However, the pattern of tumour volume on case-to-case comparison elicited more cases with larger volumes during the pandemic periods. Referral pathways of diagnosed cancer cervix was not affected during the pandemic in Oxfordshire. Therapeutic treatment numbers were unchanged – but some changes in tumour volume were likely the reason for the impression more such cases. Whether the stage shift noted here is representative of the wider population requires further studies. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer generally presents at an early stage affording a high rate of surgical cure. Early in the Covid-19 pandemic it was suggested that treatment of tumors with favorable pathologic features might safely be delayed. Objective: We hypothesized that disruption to health care services during the pandemic would impact the stage at presentation for these patients. Here we compare the stage at presentation of Endometrial Cancer in the months immediately preceding the pandemic to the stage at presentation during the pandemic. Study design: Charts of patients presenting with Endometrial Cancer between January 1, 2018 and April 30, 2022 were reviewed. March 1, 2020 separated the “pre-pandemic” era from the “pandemic” era. Data was collected regarding patient age, body mass index (BMI), tumor stage, histology, grade, size, and depth of invasion. Results: 322 of 374 (86.09%) of surgically staged patients presented with FIGO stage I disease “pre-pandemic” compared to 263 of 329 (71.73%) of surgically staged patients in the “pandemic” cohort (p =.029). 2.08% pre-pandemic compared to 5.48% during the pandemic presented with FIGO stage IV (p =.015). Conclusion: We found a significant difference in the stage at presentation in endometrial cancer patients, a statistic which may be attributed to the disruption of healthcare services caused by the Covid-19 pandemic.

Aim: Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. Method: This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan–Meier curve was used to analyse the prognosis of two groups: cN(+)pN(−); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(−)pN(−); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. Results: Among pN(−) cases, the 5‐year recurrence‐free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(−) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02–4.27, p = 0.04). Conclusion: Preoperatively over‐staged cN cases had a poorer prognosis than cases without over‐staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background There are many reports on the choice of treatment for and prognosis of left-sided obstructive colorectal cancer; however, few studies have focused on the prognostic factors of left-sided obstructive colorectal cancer. Therefore, we analyzed the prognostic factors using a post hoc analysis of a retrospective multicenter study in Japan. Methods A total of 301 patients were enrolled in this study to investigate the prognostic factors for relapse-free survival. The relationships between sex, age, decompression for bridge to surgery, depth of invasion, lymph node metastasis, postoperative complications, adjuvant chemotherapy, carcinoembryonic antigen, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, and relapse-free survival were examined. Results No change in the decompression method, T3 cancer, negative postoperative complications (grades 0–1 of Clavien-Dindo classification), and adjuvant chemotherapy during Stage III indicated a significantly better prognosis in a Cox univariate analysis. Lymph node metastasis was not selected as a prognostic factor. Excluding patients with

Objective: To summarize stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system, and to investigate prognostic factors influencing Stage IIIC1., Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to February 6, 2024. The analysis was conducted using STATA 16.0., Results: A total of 25 studies with 82954 cervical cancer patients were included in the analysis. The migration rates to FIGO 2018 Stage IIIC ranged from 18% to 37% for early-stage tumors (Stage IB to IIA) in FIGO 2009, and from 32% to 52% for advanced stage tumors (Stage IIB to IIIB). The overall survival (OS) for Stage IIIC1 is poorer compared to Stage IB1 (HR 0.53, 95% CI 0.35-0.80, p=0.003) and Stage IB2 (HR 0.61, 95% CI 0.43-0.85, p=0.004). It is comparable to Stage IB3, yet it shows better survival outcomes than Stages IIB (HR 2.91, 95% CI 1.01-8.39, p=0.047), IIIA (HR 1.96, 95% CI 1.78-2.17, p=0.000), and IIIB (HR 1.56, 95% CI 1.04-2.35, p=0.031). Tumors size ≥4cm (HR 1.45, 95% CI 1.10-1.92, p=0.00), metastatic lymph node ≥ 3 (HR 2.21, 95% CI 1.56-3.15, p=0.000) and T stage are prognostic factors for OS of Stage IIIC1., Conclusions: The migration rates to FIGO 2018 Stage IIIC varied between 18% and 52% for patients initially classified under FIGO 2009 Stages IB1 to IIIB. The FIGO 2018 staging system underscores the pivotal role of lymph node metastasis in predicting prognosis and provides valuable insights into the distinct prognostic implications associated with different stages, particularly for early stages. For advanced stages, incorporation of tumor-related factors such as T stage might better elucidate survival differences and guide clinical treatment decisions., Protocol Registration: CRD 42023451793., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Chen, Zheng, Tan and Chen.)

Several clinical trials have been revolutionizing the perioperative treatment of early-stage non-small cell lung cancer (NSCLC). Many of these clinical trials involve cancer immunotherapies with antibody drugs that block the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand PD-L1. While these new treatments are expected to improve the treatment outcome of NSCLC patients after pulmonary resection, several major clinical questions remain, including the appropriate timing of immunotherapy (neoadjuvant, adjuvant, or both) and the identification of patients who should be treated with neoadjuvant and/or adjuvant immunotherapies, because some early-stage NSCLC patients are cured by surgical resection alone. In addition, immunotherapy may induce immune-related adverse events that will require permanent treatment in some patients. Based on this fact as well, it is desirable to select appropriate patients for neoadjuvant/adjuvant immunotherapies. So far, data from several important trials have been published, with findings demonstrating the efficacy of adjuvant atezolizumab (IMpower010 trial), neoadjuvant nivolumab plus platinum-doublet chemotherapy (CheckMate816 trial), and several perioperative (neoadjuvant plus adjuvant) immunotherapies (AEGEAN, KEYNOTE-671, NADIM II, and Neotorch trials). In addition to these key trials, numerous clinical trials have reported a wealth of data, although most of the above clinical questions have not been completely answered yet. Because there are so many ongoing clinical trials in this field, a comprehensive understanding of the results and/or contents of these trials is necessary to explore answers to the clinical questions above as well as to plan a new clinical trial. In this review, we comprehensively summarize the recent data obtained from clinical trials addressing such questions.

Purpose: To audit the diagnostic accuracy of MRI for staging early and polyp rectal cancers with the purpose of identifying scope for service improvement. Methods: This is an IRB approved retrospective study of patients who underwent staging MRI for rectal growths followed by upfront TME type surgery or local excision without neoadjuvant therapy between 2018 and 2021. MR-T-stage was compared with surgical histopathology. The degree of stage migration in the multidisciplinary team meetings (MDT) was assessed and training needs were identified. Results: 53 patients (32 males) with a mean (SD) age of 56.7 (13.6) years with 54 rectal lesions and underwent trans-anal excision (n = 18) or upfront surgery (n = 35) were included. Pathology showed < / = pT1 stage in n = 18 and > / = pT2 stage in n = 36. Radio-pathological concordance rate was 38.9% and 74.1%, respectively, for primary reports and MDT reads, respectively, and during MDT, the rates improved by 44.5% and 30.5% for < / = pT1 and > / = pT2 stages ,respectively. The overall T-stage migration rate at MDT was 44.6% (25/54) and the migration rate was higher (61.1%) for < / = pT1 stage lesions. The best sensitivity, specificity, PPV, NPV and accuracy of MRI for T-staging was 83.3%, 91.6%, 83.3%, 91.6% and 88.8%, respectively. Conclusion: Radio-pathological correlation for MRI T-stage is excellent for MDT reads by experienced radiologists. MDT reads lead to significant down-staging of T-stage in polyp and early rectal cancer thereby improving radio-path correlation. [ABSTRACT FROM AUTHOR]

Background: With increasing availability of data on outcomes of surgery for prostate cancer, the profile of patients undergoing robot-assisted radical prostatectomy (RARP) has changed over the past decade. This impacts the decision-making process for surgeons and patients, particularly in low-incidence regions of Asia. Our institution was among the first in Asia to acquire a da Vinci surgical robot in 2005. We evaluated the changes in the clinical and pathology profile of patients undergoing RARP at our institution over the past 15 years (2005-2019). Methods: A retrospective analysis of patients undergoing RARP between April 2005 and December 2019 was conducted from the hospital database. The patients were divided into two groups; patients undergoing RARP from April 2005 to December 2012 (Group I, first 8 years) and January 2013 to December 2019 (Group II, next 7 years). The perioperative characteristics were compared between these two groups to assess changes in their profile and outcome. Results: Four hundred forty-seven patients were included in this study; 244 (54.6%) in Group I and 203 (45.4%) in Group II. The median prostate specific antigen in Group II was significantly higher than that in Group I (14.5 vs. 11.7 ng/ml, P = 0.016). Unfavorable pathological characteristics, i.e., Gleason Grade ≥3, perineural invasion, and the margin positivity rate increased substantially from 18.5% to 37.5%, 20.5% to 36.9%, and 15.2% to 26.6%, respectively, in Group II compared with Group I. More patients in Group II received adjuvant therapy than in Group I (P < 0.001). Conclusion: There has been a change in profile of patients undergoing RARP and patients with more unfavorable disease characteristics such as higher prostate specific antigen and tumor grade are undergoing surgery. In line with international trends, the number of patients with low-grade disease undergoing surgery has substantially decreased. Multimodal treatment with adjuvant therapy is increasingly used, particularly in high-risk disease.

Abstract Background The main negative prognostic factors in patients with rectal cancer after radical treatment include regional lymph node involvement, lymphovascular invasion, and perineural invasion. However, some patients still develop cancer recurrence despite the absence of the above risk factors. The aim of the study was to assess clinicopathological factors influencing long-term oncologic outcomes in ypN0M0 rectal cancer patients after neoadjuvant therapy and radical anterior resection. Methods A retrospective survival analysis was performed on a group of 195 patients. We assessed clinicopathological factors which included tumor regression grade, number of lymph nodes in the specimen, Charlson comorbidity index (CCI), and colorectal anastomotic leakage (AL). Results In the univariate analysis, AL and CCI > 3 had a significant negative impact on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). After the division of ALs into early and late ALs, it was found that only patients with late ALs had a significantly worse survival. The multivariate Cox regression analysis showed that CCI > 3 was a significant adverse risk factor for DFS (HR 5.78, 95% CI 2.15–15.51, p < 0.001), DSS (HR 7.25, 95% CI 2.25–23.39, p < 0.001), and OS (HR 3.9, 95% CI 1.72–8.85, p = 0.001). Similarly, late ALs had a significant negative impact on the risk of DFS (HR 5.05, 95% CI 1.97–12.93, p < 0.001), DSS (HR 10.84, 95% CI 3.44–34.18, p < 0.001), and OS (HR 4.3, 95% CI 1.94–9.53, p < 0.001). Conclusions Late AL and CCI > 3 are the factors that may have an impact on long-term oncologic outcomes. The impact of lymph node yield on understaging was not demonstrated.

The impact of changes in diagnostic activity and treatment options on prostate cancer epidemiology remains a subject of debate. Newly published long-term survival outcomes may not represent contemporary patients and new perspectives are in demand. All men dying in Denmark with prostate cancer diagnosis during a 10-year period were analyzed to address the stage migration of and time lived with prostate cancer diagnosis. All male deaths in Denmark between 2007 and 2016 (n = 261,657) were obtained and crosslinked with The Danish Prostate Cancer Registry (DaPCaR) and the Danish Cancer Registry. Correlation in diagnostic age and stage (localized, locally advanced, metastatic), age at death and cause of death were investigated by Kruskal-Wallis test and linear regression in 15,692 men diagnosed with prostate cancer. Prostate cancer mortality remained stable during the study period. Among the men who died of prostate cancer, 65% had locally advanced or metastatic disease at diagnosis. Age at diagnosis declined in men diagnosed with localized disease and remained constant in men with locally advanced or metastatic disease. Age at death increased in all men. Despite increased efforts to detect prostate cancer early, two-thirds of men who die from prostate cancer still have advanced prostate cancer at the time of diagnosis. Our data show increased life-expectancy in men diagnosed with prostate cancer, however, this benefit must be weighed against increased time of living with the disease and overdiagnosis. The intensified treatment of elderly men and men with advanced disease may be the key to lower prostate cancer mortality. [ABSTRACT FROM AUTHOR]

Background: There are many reports on the choice of treatment for and prognosis of left-sided obstructive colorectal cancer; however, few studies have focused on the prognostic factors of left-sided obstructive colorectal cancer. Therefore, we analyzed the prognostic factors using a post hoc analysis of a retrospective multicenter study in Japan. Methods: A total of 301 patients were enrolled in this study to investigate the prognostic factors for relapse-free survival. The relationships between sex, age, decompression for bridge to surgery, depth of invasion, lymph node metastasis, postoperative complications, adjuvant chemotherapy, carcinoembryonic antigen, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, and relapse-free survival were examined. Results: No change in the decompression method, T3 cancer, negative postoperative complications (grades 0–1 of Clavien-Dindo classification), and adjuvant chemotherapy during Stage III indicated a significantly better prognosis in a Cox univariate analysis. Lymph node metastasis was not selected as a prognostic factor. Excluding patients with <12 harvested lymph nodes (possible stage migration), lymph node metastasis was determined as a prognostic factor. In a Cox multivariate analysis, change in the decompression method, depth of invasion, lymph node metastasis (excluding N0 cases with <12 harvested lymph nodes), and adjuvant chemotherapy were prognostic factors. Conclusions: Similar to those in nonobstructive colorectal cancer, depth of invasion and lymph node metastasis were prognostic factors in left-sided obstructive colorectal cancer, and patients with <12 dissected lymph nodes experienced stage migration. Stage migration may result in disadvantages, such as not being able to receive adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women. Staging plays an important role in treatment planning. In the staging system published by AJCC in 2002, micrometastasis, the total number of metastatic lymph nodes, internal mammarian and supraclavicular lymph node metastases, and level III (apical) lymph node metastases were incorporated to the staging system. These modifications are likely to cause upstaging and changes in treatment plans, precisely in patients previously considered as stage II. This study aimed to investigate the outcomes of update in staging system in terms of mortality and morbidity. The records of 150 patients who underwent surgery for stage II breast cancer were retrospectively reviewed. The patients who were accepted as stage II according to the previous staging systems and planned to be treated accordingly were re-evaluated according to the newly updated staging system. Patients with and without stage change were compared in terms of mortality, local and systemic recurrence, and disease-free survival. We found that 41 (27.3%) of the patients who were accepted as stage II according to the previous staging systems had been upstaged in the new staging system. The relationship between stage migration and tumor diameter was statistically significant. Thirty-one patients (20.7%) had recurrence during follow-up. We found that most of the patients with recurrence (77.4%) had stage migration. There was a statistically significant relationship between apical lymph node involvement and recurrence. Updates in staging system of breast cancer cause stage migration in a significant proportion of patients with stage II breast cancer and are likely to lead to a change in treatment plans in some patients. Stage migration also has an impact on prognosis. In fact, recurrence is more common in patients with stage migration. [Med-Science 2020; 9(3.000): 579-84]

PURPOSE: To analyse the prognostic factors for eye salvage for eyes with intra-ocular retinoblastoma (RB) that is resistant to systemic chemotherapy and focal therapy by external beam radiation therapy (EBRT). METHODS: A retrospective analysis of 28 eyes with intra-ocular RB that was resistant for systemic chemotherapy and focal consolidation therapy and received EBRT. Outcome measures included tumor stage at diagnosis, stage migration, type of tumor seeds, treatment modalities, eye globe salvage, metastasis, and survival. RESULTS: Most of the patients (83%) had bilateral RB, and 42% were females. All eyes were treated initially by combination of systemic chemotherapy and focal consolidation therapy. The dose of EBRT was 45 Gy. The mean follow-up was 6.5 years, and the overall eye globe salvage rate post EBRT was 46%: 67% (2/3) for group B, 71% (5/7) for group C, and 33% (6/18) for group D. Patient's gender, tumor site, laterality, and tumor stage at diagnosis were not significant prognostic factors (p> 0.05) for final outcome. The significant poor prognostic factors were tumor stage migration during systemic chemotherapy (p= 0.03) and presence of vitreous seeds at time of EBRT (p=0.001). Post EBRT complication rate was 68% (19/28) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), radiation retinopathy (2), and second malignancy (2). CONCLUSION: EBRT is an alternative for enucleation when RB is resistant to combined chemoreduction/focal consolidation therapy in absence in vitreous seeds. The known risks for EBRT are not justified for patients with unilateral RB and for those who have functional vision in the other eye.

Objective: Limited progress has occurred in treating operable human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). Accessing timely care remains challenging in public health care systems, potentially resulting in disease progression before treatment initiation., Study Design: A prospective cohort of patients receiving neoadjuvant capecitabine (NC) was compared to stage-matched patients undergoing standard of care (SC)., Setting: This study was performed at 2 academic centers in Montreal, Canada., Methods: To ascertain the effect of 2 cycles of NC in operable HPV-negative HNSCC patients on clinical-to-pathologic stage migration. Comparison to an SC group was performed to site and TNM stage matched patients. Pathologic treatment response was measured using the modified Ryan score., Results: We compared 16 NC patients (11 oral cavity, 3 skin, 2 larynx) with 32 SC patients. Ten NC patients exhibited a pathologic response (1 complete, 3 major, 6 minor). Clinical-to-pathologic stage migration differed significantly between NC and SC groups: downstage (6 vs 1), upstage (3 vs 14), no change (7 vs 17, P = .0047). There was no severe treatment toxicity related to capecitabine. All patients in the NC group underwent surgery., Conclusion: NC followed by surgery demonstrates measurable pathologic response in HPV-negative HNSCC, suggesting potential utility in resource-limited health care settings., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

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Purpose: This retrospective analysis focuses on treatment stage migration in patients with hepatocellular carcinoma (HCC) to identify successful treatment sequences in a large cohort of real-world patients. Methods: 1369 HCC patients referred from January 1993 to January 2020 to the tertiary center of the Heidelberg University Hospital, Germany were analyzed for initial and subsequent treatment patterns, and overall survival. Results: The most common initial treatment was transarterial chemoembolization (TACE, n = 455, 39.3%) followed by hepatic resection (n = 303, 26.1%) and systemic therapy (n = 200, 17.3%), whereas the most common 2nd treatment modality was liver transplantation (n = 215, 33.2%) followed by systemic therapy (n = 177, 27.3%) and TACE (n = 85, 13.1%). Kaplan–Meier analysis revealed by far the best prognosis for liver transplantation recipients (median overall survival not reached), followed by patients with hepatic resection (11.1 years). Patients receiving systemic therapy as their first treatment had the shortest median overall survival (1.7 years; P < 0.0001). When three or more treatment sequences preceded liver transplantation, patients had a significant shorter median overall survival (1st seq.: not reached; 2nd seq.: 12.4 years; 3rd seq.: 11.1 years; beyond 3 sequences: 5.5 years; P = 0.01). Conclusion: TACE was the most common initial intervention, whereas liver transplantation was the most frequent 2nd treatment. While liver transplantation and hepatic resection were associated with the best median overall survival, the timing of liver transplantation within the treatment sequence strongly affected median survival. [ABSTRACT FROM AUTHOR]

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan‐Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P =.171). However, the ELNs ≥ 30 group had a better disease‐free survival (DFS) outcome compared with the others (all P <.05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182‐0.866, P =.020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152‐0.860, P =.021) and pT4 patients (HR = 0.484, 95%CI: 0.277‐0.844, P =.011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C‐index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000‐2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients. [ABSTRACT FROM AUTHOR]

Introduction The COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology. Material and methods Consecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year. Results A total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19. Conclusions Our results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control. [ABSTRACT FROM AUTHOR]

Expanding loco-regional nodes harvesting is expected to increase survival. This improvement may be associated to stage migration (SM). However, the great bulk of harvested lymph nodes observed in large dissections is negative. 830 patients who received R0 gastrectomy for adenocarcinoma were included. pN+ patients with <26 nodes (n = 209) were included for a simulation to "offer 26 nodes" - SM (proportional and exponential based) was simulated and analysed through machine learning algorithms. Overall Survival (OS), in native and simulated stages, were compared. OS of extended lymphadenectomies (pN+, D ≥ 26, n = 273) was compared with the simulated curves. OS of patients in the following dissection intervals of negative nodes were compared: <16 (n = 233), 16–25 (n = 258), ≥26 (n = 339). After simulation to 26 nodes (pN+, D < 26 patients, n = 209), staging was recomputed. OS of native vs simulated early-stages (I-II) and advanced stages (III) were not different (p > 0.05). OS of patients with lymphadenectomy (≥26) was better than simulated for early and advanced stages (p = 0.008; p = 0.005). OS of patients included in distinct intervals of negative lymph nodes were different (p < 0.001). These intervals were an independent prognostic factor (multivariate analysis). The influence of Stage Migration was null in this set of simulations and Will Rogers phenomenon was not observed. Extended dissection performed better in OS. But the influence of the number of negative nodes, even in large dissections, was highlighted. By emphasizing the role of negative nodes, we aim to facilitate more informed decision-making in management of gastric cancer patients, ultimately leading to improved treatment outcomes and patient care. [ABSTRACT FROM AUTHOR]

Background: The main negative prognostic factors in patients with rectal cancer after radical treatment include regional lymph node involvement, lymphovascular invasion, and perineural invasion. However, some patients still develop cancer recurrence despite the absence of the above risk factors. The aim of the study was to assess clinicopathological factors influencing long-term oncologic outcomes in ypN0M0 rectal cancer patients after neoadjuvant therapy and radical anterior resection. Methods: A retrospective survival analysis was performed on a group of 195 patients. We assessed clinicopathological factors which included tumor regression grade, number of lymph nodes in the specimen, Charlson comorbidity index (CCI), and colorectal anastomotic leakage (AL). Results: In the univariate analysis, AL and CCI > 3 had a significant negative impact on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). After the division of ALs into early and late ALs, it was found that only patients with late ALs had a significantly worse survival. The multivariate Cox regression analysis showed that CCI > 3 was a significant adverse risk factor for DFS (HR 5.78, 95% CI 2.15–15.51, p < 0.001), DSS (HR 7.25, 95% CI 2.25–23.39, p < 0.001), and OS (HR 3.9, 95% CI 1.72–8.85, p = 0.001). Similarly, late ALs had a significant negative impact on the risk of DFS (HR 5.05, 95% CI 1.97–12.93, p < 0.001), DSS (HR 10.84, 95% CI 3.44–34.18, p < 0.001), and OS (HR 4.3, 95% CI 1.94–9.53, p < 0.001). Conclusions: Late AL and CCI > 3 are the factors that may have an impact on long-term oncologic outcomes. The impact of lymph node yield on understaging was not demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated how the changes in Gleason grading affected the long-term outcomes of a large prostatectomy cohort.Methods: We obtained long-term follow-up (16.7 years) in 581 patients having undergone radical retropubic prostatectomy between 1985 and 1995. We excluded those with seminal vesicle and/or lymphatic involvement. We regraded the specimens according to contemporary guidelines and compared how this affected outcomes compared with their original (pre-1995) Gleason scoring. In total, 499 patients were evaluable.Results: A Gleason score of 6 or less declined from 73% to 29%, and the number increased from 25% to 63% for a Gleason score of 7 and from 5% to 8% for a Gleason score of 8 to 9. As a result, for a Gleason score less than 7, biochemical failure decreased from 28% to 23%, metastatic disease 5% to 2%, and prostate cancer death from 5% to 3%. The same results were 50% to 37%, 11% to 7%, and 10% to 6% for a Gleason score of 7 and 86% to 71%, 43% to 32%, and 29% to 26% for a Gleason score more than 7, respectively. With the most recent grade grouping, for groups 1 to 5, biochemical failure occurred in 23%, 32%, 45%, 69%, and 78%, respectively. Metastatic disease occurred in 2%, 4%, 12%, 24%, and 56%, respectively. Prostate cancer-related death occurred in 2%, 4%, 9%, 21%, and 44%, respectively.Conclusions: The revised Gleason scores improved the outcomes in all risk groups. Based on Gleason score, patients with prostate cancer will appear to have better outcomes than they did before 2005, making any comparison tenable. The current grading system shows a consistent increased risk in biochemical failure, metastatic disease, and prostate cancer-related death with each successive grade. [ABSTRACT FROM AUTHOR]

• Wait time is detrimental to lung cancer patients due to disease progression. • Successive PET/CT scans can assess disease stage migration. • Metastatic and nodal disease progression occur much sooner for adenocarcinoma or stage IIIB patients. • Reducing wait times may have a positive impact on treatment outcome and survival. Patients with non-small cell lung cancer (NSCLC) can experience rapid disease progression between initial staging FDG-PET scans and commencement of curative-intent radiotherapy (RT). Previous studies that estimated stage migration rates by comparing staging PET/CT and treatment-planning PET/CT images were limited by small sample sizes. This multicenter, international study combined prospective data from five institutions for PET-staged patients with NSCLC who were intended to receive curative-intent RT. TNM status was compared for staging and RT planning scans and the probability of TNM status and overall stage migration was analyzed as a function of the interval between PET/CT scans. The impacts of N classification, overall stage, and pathology were also studied. Pooled data from 181 patients were analyzed. The median interval between PET/CT scans was 42 days (range, 2–208). Upstaging occurred in 32 % of patients. The overall rate of stage migration was higher for patients presenting with initial stage IIIB/IIIC disease (p = 0.006) and patients with N2−3 nodal disease (p = 0.019). Upstaging to M1 disease was significantly associated with initial stage IIIB/IIIC disease (HR = 15.2) and adenocarcinoma (HR = 10) histology. Longer intervals between imaging and treatment in patients with NSCLC were associated with high rates disease progression with consequent risks of geographic miss in RT planning and futile treatment in patients with M1 disease. Patients with more extensive initial nodal involvement and those with adenocarcinoma had the highest rates of stage migration. Dedicated RT planning PET/CT imaging is recommended, especially if >3 weeks have elapsed after initial staging. [ABSTRACT FROM AUTHOR]

BackgroundThe impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear.MethodsConsecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr,

BackgroundWhile most guidelines advocate D2 lymphadenectomy for non-metastatic gastric adenocarcinoma (nmGaC), it is not always performed as standard of care outside East Asia. The recommended minimal examined lymph node (ELN) count in nmGaC to stage cancer accurately varies largely across guidelines, and the optimal count to satisfactorily stratify patient survival has yet to be determined. This large cohort study aimed at robustly defining the minimal and optimal thresholds of examined lymph node (ELN) number in non-metastatic gastric adenocarcinoma (nmGaC).MethodsData on nmGaC patients operated in 2010–2016 and surviving ≥3 months were retrieved from the US SEER-18 Program and a Chinese multi-institutional gastric cancer database (MIGC). The correlation of ELN count with stage migration and patient survival were quantified with the use of the multivariable-adjusted logistic and proportional hazards Cox models, respectively. The sequences of odds ratios (ORs) and hazard ratios (HRs) for each additional ELN were smoothed, and the structural breakpoints were determined.ResultsTogether 7,228 patients from the US and 1,468 from China were analyzed, encompassing 23,114 person-years of follow-up. The mean ELN count was 20 in the US and 30 in China. With more ELNs, both cohorts significantly showed proportional increases from lower to higher nodal stage (ORSEER = 1.03, 95%-CI = 1.03–1.04; ORMIGC = 1.02, 95%-CI = 1.02–1.03) and sequential enhancements in postoperative survival (HRSEER = 0.97, 95%-CI = 0.97–0.97; HRMIGC = 0.98, 95%-CI = 0.97–0.99). Correlations for both stage migration and survival were still significant in most subgroups by patient, cancer, and management factors. Breakpoint analyses revealed a minimum threshold ELN count of 17 and an optimum count of 33, which were validated in both cohorts with good efficacy to differentiate probabilities of both stage migration and survival.ConclusionIn resected nmGaC patients with anticipated survival ≥3 months, more ELNs are correlated with more accurate staging, which may partly explain the survival correlation. This observational investigation does not indicate causality. Our findings robustly conclude 17 ELNs as the minimum and propose 33 ELNs as the optimum thresholds, to assess the quality of lymph node examination and to stratify postsurgical survival.

The impact of changes in diagnostic activity and treatment options on prostate cancer epidemiology remains a subject of debate. Newly published long-term survival outcomes may not represent contemporary patients and new perspectives are in demand. All men dying in Denmark with prostate cancer diagnosis during a 10-year period were analyzed to address the stage migration of and time lived with prostate cancer diagnosis. All male deaths in Denmark between 2007 and 2016 (n = 261,657) were obtained and crosslinked with The Danish Prostate Cancer Registry (DaPCaR) and the Danish Cancer Registry. Correlation in diagnostic age and stage (localized, locally advanced, metastatic), age at death and cause of death were investigated by Kruskal-Wallis test and linear regression in 15,692 men diagnosed with prostate cancer. Prostate cancer mortality remained stable during the study period. Among the men who died of prostate cancer, 65% had locally advanced or metastatic disease at diagnosis. Age at diagnosis declined in men diagnosed with localized disease and remained constant in men with locally advanced or metastatic disease. Age at death increased in all men. Despite increased efforts to detect prostate cancer early, two-thirds of men who die from prostate cancer still have advanced prostate cancer at the time of diagnosis. Our data show increased life-expectancy in men diagnosed with prostate cancer, however, this benefit must be weighed against increased time of living with the disease and overdiagnosis. The intensified treatment of elderly men and men with advanced disease may be the key to lower prostate cancer mortality.

Background: The impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear. Methods: Consecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr, <16 LNs) and sufficient LNs removed (SLNr, ≥16 LNs). Performance of the prediction systems was evaluated using the Likelihood ratio χ2 test, Akaike information criterion (AIC), Harrell's concordance index (C-index), and area under the receiver operating characteristic curves (AUC). Results: The OS of patients were significantly longer in those with SLNr relative to those with ILNr (for stage IIIA, 68.2 vs. 43.2 months, P = 0.042; for stage IIIB, 43.7 vs. 24.9 months, P < 0.001; for stage IIIC, 23.9 vs. 8.3 months, P < 0.001; and for total stage III, 37.7 vs. 21.7 months, P < 0.001). However, the OS were similar between stage IIIA patients with ILNr and stage IIIB patients with SLNr (P = 0.928), between IIIB patients with ILNr and IIIC patients with SLNr (P = 0.962), and IIIC patients with ILNr and stage IV (P = 0.668), respectively. A substage increase in the AJCC classification system, from IIIA to IIIB, from IIIB to IIIC, and from IIIC to IV in patients with ILNr, enhanced the accuracy of prognostic prediction in patients with stage III gastric cancer compared to the current TNM system (Likelihood ratio χ2, 188.6 vs. 184.8; AIC, 4336.4 vs. 4340.6; C-index, 0.695 vs. 0.679, P = 0.002). The ROC curves revealed that the performance of prognostic prediction was better in the new prediction system (AUC = 0.699) compared with the current TNM system (AUC = 0.676). Conclusions: ILNr (LNs <16) impairs the long-term outcomes of stage III gastric cancer underwent adjuvant chemotherapy. The status of LNs removal adds values to the current TNM system in prognostic prediction of stage III gastric cancer. [ABSTRACT FROM AUTHOR]

Background: While most guidelines advocate D2 lymphadenectomy for non-metastatic gastric adenocarcinoma (nmGaC), it is not always performed as standard of care outside East Asia. The recommended minimal examined lymph node (ELN) count in nmGaC to stage cancer accurately varies largely across guidelines, and the optimal count to satisfactorily stratify patient survival has yet to be determined. This large cohort study aimed at robustly defining the minimal and optimal thresholds of examined lymph node (ELN) number in non-metastatic gastric adenocarcinoma (nmGaC). Methods: Data on nmGaC patients operated in 2010–2016 and surviving ≥3 months were retrieved from the US SEER-18 Program and a Chinese multi-institutional gastric cancer database (MIGC). The correlation of ELN count with stage migration and patient survival were quantified with the use of the multivariable-adjusted logistic and proportional hazards Cox models, respectively. The sequences of odds ratios (ORs) and hazard ratios (HRs) for each additional ELN were smoothed, and the structural breakpoints were determined. Results: Together 7,228 patients from the US and 1,468 from China were analyzed, encompassing 23,114 person-years of follow-up. The mean ELN count was 20 in the US and 30 in China. With more ELNs, both cohorts significantly showed proportional increases from lower to higher nodal stage (ORSEER = 1.03, 95%-CI = 1.03–1.04; ORMIGC = 1.02, 95%-CI = 1.02–1.03) and sequential enhancements in postoperative survival (HRSEER = 0.97, 95%-CI = 0.97–0.97; HRMIGC = 0.98, 95%-CI = 0.97–0.99). Correlations for both stage migration and survival were still significant in most subgroups by patient, cancer, and management factors. Breakpoint analyses revealed a minimum threshold ELN count of 17 and an optimum count of 33, which were validated in both cohorts with good efficacy to differentiate probabilities of both stage migration and survival. Conclusion: In resected nmGaC patients with anticipated survival ≥3 months, more ELNs are correlated with more accurate staging, which may partly explain the survival correlation. This observational investigation does not indicate causality. Our findings robustly conclude 17 ELNs as the minimum and propose 33 ELNs as the optimum thresholds, to assess the quality of lymph node examination and to stratify postsurgical survival. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. Methods: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. Results: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86–1.00) and 0.95 (0.88–0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). Conclusions: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to determine the immunologic role of lymph node (LN) and stage migration by assessing LN count and metastatic LN count. Methods A total of 2,117 patients with gastric adenocarcinoma located in the body and antrum who underwent distal/subtotal gastrectomy with D2 LN dissection between January 1, 1998 and December 31, 2008 were enrolled. LN count and number of metastases were determined in the N1 tier (area of D1 dissection) and N2 tier (area of D2 dissection). The lower and upper quartiles of LN counts in the same pN stage were grouped to compare the prognosis and LN positivity according to the LN tier. Results Stage migration from N1 tier to N2 tier occurred in 3.2% of cases. The 5-year disease-specific survival rates of the upper and lower LN count groups within the N1 tier were 91.0% and 86.7% (P=0.01), respectively. LN positivity in the N2 tier of the lower LN count group was higher than that of the upper LN count group (14.1% vs. 8.2%, P

To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation. • Local stage of advanced cervical cancer changes in 27% comparing MRI and clinical examination. • For treatment allocation important clinical stages IB1-IIA2 changed to IIB on MRI in 31%. • Pelvic wall/bladder infiltration vary considerably, likely due to different definitions for clinical and imaging findings. • 50% of this cohort are allocated to stage IIIC with FIGO 2018, obscuring local tumour extent. • TNM offers the most differentiated stage allocation with 26 subgroups in this cohort. [ABSTRACT FROM AUTHOR]

PURPOSE: To analyse the prognostic factors for eye salvage for eyes with intra-ocular retinoblastoma (RB) that is resistant to systemic chemotherapy and focal therapy by external beam radiation therapy (EBRT). METHODS: A retrospective analysis of 28 eyes with intra-ocular RB that was resistant for systemic chemotherapy and focal consolidation therapy and received EBRT. Outcome measures included tumor stage at diagnosis, stage migration, type of tumor seeds, treatment modalities, eye globe salvage, metastasis, and survival. RESULTS: Most of the patients (83%) had bilateral RB, and 42% were females. All eyes were treated initially by combination of systemic chemotherapy and focal consolidation therapy. The dose of EBRT was 45 Gy. The mean follow-up was 6.5 years, and the overall eye globe salvage rate post EBRT was 46%: 67% (2/3) for group B, 71% (5/7) for group C, and 33% (6/18) for group D. Patient's gender, tumor site, laterality, and tumor stage at diagnosis were not significant prognostic factors (p> 0.05) for final outcome. The significant poor prognostic factors were tumor stage migration during systemic chemotherapy (p= 0.03) and presence of vitreous seeds at time of EBRT (p=0.001). Post EBRT complication rate was 68% (19/28) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), radiation retinopathy (2), and second malignancy (2). CONCLUSION: EBRT is an alternative for enucleation when RB is resistant to combined chemoreduction/focal consolidation therapy in absence in vitreous seeds. The known risks for EBRT are not justified for patients with unilateral RB and for those who have functional vision in the other eye. [ABSTRACT FROM AUTHOR]

In its basic form, the Will Rogers phenomenon takes place when an increase in the average value of each of two sets is achieved by moving an element from one set to another. This leads to the conclusion that there has been an improvement, when in fact essentially nothing has changed. Extended versions of this phenomenon can occur in epidemiological studies, rendering their results unreliable. After describing epidemiological and clinical studies that have been affected by the Will Rogers phenomenon, this paper presents a simple method to correct for it. The method involves introducing a transition matrix between the two sets and taking probability weighted expectations. Two real‐world biometrical examples, based on migration economics and breast cancer epidemiology, are given and improvements against a naïve analysis are demonstrated. In the cancer epidemiology example, we take account of estimation uncertainty. We also discuss briefly some limitations associated with our method. [ABSTRACT FROM AUTHOR]

We sought to identify the reliability of AJCC clinical staging was in comparison to pathologic staging in surgically resected patients with pancreatic cancer. We used the National Cancer Database Pancreas from 2004 to 2016 and evaluated patients who underwent resection for PDAC with all documented components of clinical and pathologic stage. We first evaluated the distribution of overall clinical stage and pathologic stage and then evaluated for stage migration by assessing the number of patients who shifted from a clinical stage group to a respective pathologic stage group. To further characterize the migratory pattern, we assessed the distribution of clinical and pathologic T-stage and N-stage. In our cohort of 28,338 patients who underwent resection for PDAC, AJCC clinical staging did not reliably predict pathologic stage. Stage migration after resection was responsible for discrepancies between the distribution of overall clinical stage and pathologic stage. The predominant migration was from patients with clinical stage I disease to pathologic stage II disease. Most patients with clinical T1 and T2 disease were upstaged to pathologic T3 disease and over half of patients with clinical N0 disease were upstaged to pathologic N1 disease after resection. Clinical staging appears to overrepresent early T1, T2, and N0 disease, and underrepresent T3 and N1 disease. [ABSTRACT FROM AUTHOR]

Objectives: To test the effect of stage and grade migration on cancer specific mortality (CSM) in renal cell carcinoma (RCC) patients, according to clear cell (ccRCC) vs. non-ccRCC histology.Methods and Materials: Within the Surveillance, Epidemiology, and End Results registry (2004-2015), we identified patients with ccRCC and non-ccRCC (papillary [papRCC], chromophobe [chRCC], sarcomatoid [sarcRCC], and collecting duct [cdRCC]). Two consecutive time groups were considered - historical (2004-2009) and contemporary era (2010-2015). Temporal trends of tumor characteristics were evaluated. Cumulative incidence plots and multivariable competing risks regression models tested the effect of year groups on CSM.Results: Overall, 24,746 and 73,228 patients with non-ccRCC and ccRCC were evaluated. Of those, 42% and 58% were recorded in historical and contemporary era. Time trend analyses showed (1) tumor size decreased for non-ccRCC (estimated annual percent changes [EAPC]: -1.1%; P <0.01) and for ccRCC (EAPC: -1.0%; P <0.01), (2) rates of G3/G4 decreased for non-ccRCC (EAPC: -0.7%; P = 0.03), but increased for ccRCC (EAPC: +1.1; P <0.01), 3) rates of node positive disease decreased for non-ccRCC (EAPC:-3.1%; P = 0.02), but were stable for ccRCC (EAPC: +0.4; P =0.5), (4) rates of metastatic disease at diagnosis decreased for non-ccRCC (EAPC: -3.2%; P <0.01), but were stable for ccRCC (EAPC: -0.6%; P = 0.1), (5) among non-ccRCC, the percentage of papRCC increased (EAPC:+1%; P <0.01), while the percentage of sarcRCC (EAPC: -7%; P <0.01) and cdRCC (EAPC: -11.2%; P <0.01) decreased. Finally, in multivariable CRR models, lower CSM was recorded for contemporary non-ccRCC (HR: 0.7; P <0.001) and ccRCC (HR: 0.8; P <0.001) patients.Conclusion: Our findings illustrate a favorable stage and grade migration and improved cancer-specific mortality in contemporary non-ccRCC. Additionally, despite absence of meaningful stage migration in ccRCC, improved cancer-specific mortality in contemporary patients was also recorded. In consequence, a 2-tiered process appears to be operational in non-ccRCC vs. a 1-tiered phenomenon in ccRCC. [ABSTRACT FROM AUTHOR]

Purpose: Several scoring systems have been proposed to predict the outcome of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). However, the application of these scores to a bridging to transplant setting is poorly validated. Evaluation of the applicability of prognostic scores for patients undergoing TACE in palliative intention vs. bridging therapy to liver transplantation (LT) is necessary. Methods: Between 2008 and 2017, 148 patients with HCC received 492 completed TACE procedures (158 for bridging to transplant; 334 TACE procedures in palliative treatment intention at our center and were analyzed retrospectively. Scores (ART, CLIP, ALBI, APRI, SNACOR, HAP, STATE score, Child–Pugh, MELD, Okuda and BCLC) were calculated and evaluated for prediction of overall survival. ROC analysis was performed to assess prediction of 3-year survival and treatment discontinuation. Results: In patients receiving TACE in palliative intention most scores predicted OS in univariate analysis but only mSNACOR score (p = 0.006), State score (p < 0.001) and Child–Pugh score (p < 0.001) revealed statistical significance in the multivariate analysis. In the bridging to LT cohort only the BCLC score revealed statistical significance (p = 0.002). Conclusions: Clinical usability of suggested scoring systems for TACE might be limited depending on the individual patient cohorts and the indication. Especially in patients receiving TACE as bridging to LT none of the scores showed sufficiently applicability. In our study Child–Pugh score, STATE score and mSNACOR score showed the best performance assessing OS in patients with TACE as palliative therapy. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognosis value of lymphatic vessel invasion (LVI) in pN0 gastric cancer patients with insufficient examined lymph nodes (ELNs).Methods: Clinicopathologic and prognostic data of pN0 gastric cancer patients with insufficient ELNs who underwent radical surgery in our institution were retrospectively studied.Results: Firstly, we confirmed that less than 16 but not less than 30 ELNs were insufficient ELNs in the present study. Of the 350 pN0 patients with < 16 ELNs, 64 patients (18.29%) had LVI. The overall survival (OS) of patients with LVI was significantly poorer than those without LVI. Multivariate analysis suggested that LVI was one of the independent factors predicting prognosis of pN0 patients with < 16 ELNs. Further analyses suggested that there were similar prognoses between pN0 patients with < 16 ELNs who had LVI and pN1 patients, and between pN0 patients with < 16 ELNs who had no LVI and pN0 patients with ≥ 16 ELNs, respectively. Therefore, we proposed a novel pN classification, in which LVI-positive pN0 gastric cancer with < 16 ELNs was classified as pN1 disease. Two-step multivariate analysis demonstrated that the novel pN classification was more suitable for prognostic assessment than the original one.Conclusions: LVI is a powerful and independent prognostic factor for pN0 gastric cancer patients with < 16 ELNs, and node-negative gastric cancer with < 16 ELNs which had LVI should be considered as node-positive disease. LVI is an effective indicator identifying patients stage migration happens to in pN0 patients with < 16 ELNs. [ABSTRACT FROM AUTHOR]