Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound.

BACKGROUND: With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study. METHODS: Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys. RESULTS: A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1-12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were "very" or "completely" satisfied with the clinical utility of the synoptic template (90.0%). CONCLUSIONS: Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

BACKGROUND: Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). METHODS: Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. RESULTS: Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p = 0.04), more than three suspicious nodes on initial US (30% vs 13%; p ≤ 0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p = 0.0004), and more positive TAD nodes (median, 2 vs 1; p ≤ 0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p ≤ 0.0001), more positive TAD nodes (OR, 1.1; p ≤ 0.0001), larger clipped node metastasis (OR, 1.1; p ≤ 0.0001), and larger residual tumor on pathology (OR, 1.1; p = 0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. CONCLUSION: Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Association of Lymph Nodes Positive Rate With the Risk of Recurrence in Patients With Stage T1 Papillary Thyroid Cancer.

The incidence of lymph node metastasis in papillary thyroid carcinoma (PTC) is common and a significant risk factor for local recurrence; however, its impact on recurrence patterns among low-risk patients remains uncertain. We aimed to elucidate the effect of metastatic lymph node on recurrence type. The medical records of 1209 patients with stage T1 PTC who underwent unilateral thyroidectomy with ipsilateral central lymph node dissection were retrospectively analyzed. The study first identified risk factors for different types of recurrence and then categorized patients as high or low risk based on their lymph node positive ratio (LNPR). The diagnostic accuracy of LNPR in predicting recurrence was compared using receiver operating characteristic (ROC) curve analysis, while differences in recurrence-free survival were assessed using the Kaplan-Meier method. During follow-up, a total of 502 (41.5%) patients had central lymph node metastasis and 52 (4.3%) patients experienced recurrence. Notably, LNPR was significantly higher in relapsed patients compared to nonrelapsed patients, with mean values of 0.45 and 0.23, respectively (P < .001). The recurrence rate of residual thyroid did not differ significantly across different T stages (P = .679), N stages (P = .415), or LNPR risk groups (P = .175). However, the recurrence rate of lymph nodes showed a significant correlation with LNPR (P < .001). The area under the ROC curves for LNPR risk stratification at 5 and 10 years were approximately 0.691 and 0.634, respectively, both of which outperformed N stage. The findings underscore the significance of LNPR's reliability as a prognostic indicator for local lymph node recurrence in patients diagnosed with T1 stage PTC.

Oncologic outcomes of de-escalating axillary treatment in clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy - A two center cohort study.

BACKGROUND: The aim of the present study was to report the 5-year axillary recurrence-free interval (aRFI) in clinically node-positive breast cancer patients treated according to a de-escalating axillary treatment protocol after neoadjuvant systemic therapy (NST). METHODS: All patients diagnosed in two hospitals between October 2014 and March 2021 were identified retrospectively. Data on diagnostic workup, treatment and follow-up was collected. Adjuvant axillary treatment was considered based on the initial staging using 18F-FDG PET/CT and the results of axillary lymph node marking with a radioactive-iodine seed protocol or a targeted axillary dissection procedure. Follow-up was updated until 27th April 2024. Kaplan-Meier curves were calculated to report the 5-year aRFI with corresponding 95 % confident intervals (95%-CI). RESULTS: A total of 199 patients were included. Axillary pathological complete response was reported in 66 (33.2 %). Based on the treatment protocol and initial clinical staging, no adjuvant axillary treatment was indicated in 30 patients (15 %), while 139 (70 %) received axillary radiotherapy without performance of an axillary lymph node dissection (ALND). The remaining 30 patients (15 %) underwent an ALND with additional locoregional radiotherapy. A median follow-up of 62 months (30-106) showed that 4 (2 %) patients experienced an axillary recurrence after 7, 8, 36 and 36 months, respectively. In all 4 patients, synchronous distant metastases were diagnosed. The estimated 5-year aRFI was 97.8 % (95%-CI 95.6-99.9 %) CONCLUSION: Although longer follow-up should be awaited before final conclusions can be drawn regarding the oncological safety of this approach, the implementation of a de-escalating axillary treatment protocol appears to be safe since the estimated 5-year aRFI is 97.8 %.

The Prognostic Value of Human Papillomavirus Status in Penile Cancer: Outcomes From a Norwegian Cohort Study.

INTRODUCTION: Penile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or the components tumor stage (pT), grade of differentiation (Grade), lymphovascular invasion (LVI), and nodular stage (pN) depend on HPV status. Also, whether the value of tumor parameters (pT, Grade, and LVI) for predicting node-positive disease depends on HPV status was investigated. PATIENTS AND METHODS: Stored tumor tissue from 226 patients treated for PSCC in Western Norway between 1973 and 2023 was investigated for HPV DNA. Histopathological variables were reevaluated according to the current TNM classification. Disease course was registered from hospital records. Inclusion of an interaction term between HPV and TNM stage groups in Cox regression enabled analysis of whether cancer-specific survival (CSS) of the stage groups depended on HPV status. This was also done separately for pT, Grade, LVI, and pN. Logistic regression with interaction terms between HPV and the tumor parameters were used to investigate if their predictive value depended on HPV status. RESULTS: HPV DNA was detected in 43% of the tumors. Stratified by HPV status, there was no significant interaction term in the Cox regression between HPV status and TNM stage groups (P = .74). Similar results were found for pT (P = .94), Grade (P = .08), LVI (P = .91) and pN (P = .77). Moreover, there were no significant interaction terms in the logistic regression between HPV status and the tumor parameters pT, Grade, and LVI (all P > .2). CONCLUSIONS: This study found that prognosis of the TNM stage groups and the components pT, Grade, LVI, and pN were not modified by HPV in PSCC. The value of pT, Grade, and LVI for predicting lymph node-positive disease was not affected by HPV status.

Wire-Free Targeted Axillary Dissection: A Pooled Analysis of 1300+ Cases Post-Neoadjuvant Systemic Therapy in Node-Positive Early Breast Cancer.

Recent advances in neoadjuvant systemic therapy (NST) have significantly improved pathologic complete response rates in early breast cancer, challenging the role of axillary lymph node dissection in nose-positive patients. Targeted axillary dissection (TAD) integrates marked lymph node biopsy (MLNB) and tracer-guided sentinel lymph node biopsy (SLNB). The introduction of new wire-free localisation markers (LMs) has streamlined TAD and increased its adoption. The primary endpoints include the successful localisation and retrieval rates of LMs. The secondary endpoints include the pathological complete response (pCR), SLNB, and MLNB concordance, as well as false-negative rates. Seventeen studies encompassing 1358 TAD procedures in 1355 met the inclusion criteria. The localisation and retrieval rate of LMs were 97% and 99%. A concordance rate of 67% (95% CI: 64-70) between SLNB and MLNB was demonstrated. Notably, 49 days (range: 0-272) was the average LM deployment time to surgery. pCR was observed in 46% (95% CI: 43-49) of cases, with no significant procedure-related complications. Omitting MLNB or SLNB would have under-staged the axilla in 15.2% or 5.4% (p = 0.0001) of cases, respectively. MLNB inclusion in axillary staging post-NST for initially node-positive patients is crucial. The radiation-free Savi Scout, with its minimal MRI artefacts, is the preferred technology for TAD.

Avelumab maintenance therapy for node-positive muscle invasive bladder cancer: a report of two cases.

Background: Muscle-invasive bladder cancer (MIBC) with nodal involvement is associated with poor prognosis and high mortality. Treatment of node-positive MIBC is complex due to disease heterogeneity and a lack of evidence-based treatment options, especially alternatives to radical cystectomy. We describe a bladder-sparing management approach involving systemic therapy followed by maintenance therapy, illustrated with two cases of node-positive MIBC. Case presentation: Two patients with node-positive MIBC received upfront gemcitabine/cisplatin chemotherapy, concurrent chemoradiotherapy (cCRT), and avelumab (immune checkpoint inhibitor) maintenance therapy. Both patients achieved complete remission without recurrence or distant metastasis post-avelumab maintenance therapy. At the last follow-up, Patient 1 (45-year-old male) was in remission for over two years, and Patient 2 (57-year-old male) was in complete remission for over one year post-chemotherapy. Avelumab treatment was well-tolerated, with no immune-related adverse events, and quality of life (QoL) was maintained. Conclusion: Both cases showed a good response and extended remission on avelumab maintenance, supporting its use in conjunction with local consolidation therapy as a bladder-preserving approach in node-positive MIBC. Further research, such as the ongoing INSPIRE trial, is required to refine treatment strategies for this patient group.

Ultrasensitive PSA: rethinking post-surgical management for node positive prostate cancer.

Introduction: Clinicians may offer patients with positive lymph nodes (pN1) and undetectable PSA following surgery for prostate cancer either observation or adjuvant therapy based on AUA, EAU, and NCCN guidelines considering standard PSA detection thresholds of <0.1ng/ml. Here we sought to investigate the outcomes of pN1 patients in the era of ultrasensitive PSA testing. Methods: We queried the Northwestern Electronic Data Warehouse for patients with prostate cancer who were pN1 at radical prostatectomy and followed with ultrasensitive PSA. Patients receiving neoadjuvant treatment were excluded. We compared clinical characteristics including age, race, pre-operative PSA, Gleason grade, tumor stage, surgical margins, and nodal specimens to identify factors associated with achievement and maintenance of an undetectable PSA (defined as <0.01 ng/mL). Statistics were performed using t-test, Mann-Whitney U test, chi-squared analysis, and logistic regression with significance defined as p<0.05. Results: From 2018-2023, 188 patients were included. Subsequently, 39 (20.7%) had a PSA decline to undetectable levels (<0.01 ng/mL) post-operatively at a median time of 63 days. Seven percent of these men (3/39) were treated with adjuvant RT + ADT with undetectable PSA levels. 13/39 (33.3%) had eventual rises in PSA to ≥0.01 ng/mL for which they underwent salvage RT with ADT. Overall, 23/39 (59%) patients achieved and maintained undetectable PSA levels without subsequent therapy at median follow-up of 24.2 mo. Compared to patients with PSA persistence after surgery or elevations to detectable levels (≥0.01 ng/mL), patients who achieved and maintained undetectable levels had lower Gleason grades (p=0.03), lower tumor stage (p<0.001), fewer positive margins (p=0.02), and fewer involved lymph nodes (p=0.02). On multivariable analysis, only primary tumor (pT) stage was associated with achieving and maintaining an undetectable PSA; pT3b disease was associated with a 6.6-fold increased chance of developing a detectable PSA (p=0.03). Conclusion: Ultrasensitive PSA can aid initiation of early salvage therapy for lymph node positive patients after radical prostatectomy while avoiding overtreatment in a significant subset. 20% of patients achieved an undetectable PSA and over half of this subset remained undetectable after 2 years.

Can Radiological Tumour Thickness Predict Pathological Prognostic Factors in Clinicoradiologically Node-Negative Oral Squamous Carcinoma? A Prospective Study.

Background: This research investigates potential connections between radiological tumour thickness determined by CT scans and various pathological prognostic factors. These factors include pathological tumour thickness (pTT), pathological depth of invasion (DOI), and positive cervical nodal metastasis. This analysis focuses on cases of clinicoradiologically node-negative squamous cell carcinoma of the buccal mucosa. Method: Sixty-one previously untreated clinicoradiologically node-negative squamous cell carcinoma of buccal mucosa were included in the study. The radiological tumour thickness in the preoperative CT scans is correlated with other prognostic factors like pathological tumour thickness, DOI and presence or absence of neck node. Result: Sixty-one patients were included in the study with a median age of 54 years (Range 27-84). Forty-two patients (68.9%) were male, and 19 were females (31.1%). There was no statistically significant difference in mean values of rTT among patients with positive or negative post-operative nodal metastases. However, a significant correlation could be established with rTT to other potential prognostic factors. Conclusion: Tumor thickness in preoperative CT scans can be used to predict post-operative prognostic factors in oral squamous cell carcinoma.

Implementation of the Targeted Axillary Dissection Procedure in Clinically Node-Positive Breast Cancer: A Retrospective Analysis.

BACKGROUND: The targeted axillary dissection (TAD) procedure is used in clinically positive lymph node (cN+) breast cancer to assess whether pathological complete response (pCR) is achieved after neoadjuvant systemic therapy (NST) to decide on de-escalation of axillary lymph node dissection (ALND). In this study, we review the implementation of the TAD procedure in a large regional breast cancer center. METHODS: All TAD procedures between 2016 and 2022 were reviewed. The TAD procedure consists of marking pre-NST the largest suspected metastatic lymph node(s) using a radioactive I-125 seed. During surgery, the marked node was excised together with a sentinel node procedure. Axillary therapy (ALND, axillary radiotherapy, or nothing) recommendations were based on the amount of suspected positive axillary lymph nodes (ALNs < 4 or ≥ 4) pre-NST and if pCR was achieved after NST. RESULTS: A total of 312 TAD procedures were successfully performed in 309 patients. In 134 (43%) cases, pCR of the TAD lymph nodes were achieved. Per treatment protocol, 43 cases (14%) did not receive any axillary treatment, 218 cases (70%) received adjuvant axillary radiotherapy, and 51 cases (16%) underwent an ALND. During a median follow-up of 2.8 years, 46 patients (14%) developed recurrence, of which 11 patients (3.5%) had axillary recurrence. CONCLUSIONS: Introduction of the TAD procedure has resulted in a reduction of 84% of previously indicated ALNDs. Moreover, 18% of cases did not receive adjuvant axillary radiotherapy. These data show that implementation of de-escalation axillary treatment with the TAD procedure appeared to be successful.

A cost-consequence model of using the 21-gene assay to identify patients with early-stage node-positive breast cancer who benefit from adjuvant chemotherapy in the Netherlands.

BACKGROUND: Patients with early-stage hormone receptor positive, human epidermal growth factor receptor-2 (HER2) negative invasive breast cancer with 1-3 positive lymph nodes (N1) often undergo surgical excisions followed by adjuvant chemotherapy (ACT). Many patients have no benefit from ACT and receive unnecessary, costly treatment often associated with short- and long-term adverse events (AEs). Gene expression profiling (GEP) assays, such as the 21-gene assay (i.e. the Oncotype DX assay), can identify patients at higher risk for recurrence who may benefit from ACT. However, the budgetary consequence of using the Oncotype DX assay versus no GEP testing in the Netherlands is unknown. Our study therefore assessed it using a cost-consequence model. METHODS: A validated model was used to create the N1 model. The model compared the costs and consequences of using the Oncotype DX assay versus no GEP testing and MammaPrint, and subsequent ACT use with corresponding costs for chemotherapy, treatment of AEs, productivity losses, GEP testing, and treatment of recurrences, according to the Oncotype DX results. The model time horizon was 5 years. RESULTS: Costs for the total population amounted to €8.0 million (M), €16.2 M, and €9.5 M, and cost per patient amounted to €13,540, €27,455, and €16,154 for using the Oncotype DX assay, no GEP testing, and MammaPrint, respectively. Total cost savings of using the Oncotype DX assay amounted to €8.2 M versus no GEP testing and €1.5 M versus MammaPrint. Using the Oncotype DX assay would result in fewer patients receiving ACT and thus fewer AEs, sick days, and hospitalizations, leading to overall cost savings compared with no GEP testing and MammaPrint. CONCLUSIONS: Implementing Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system.

Early-stage invasive breast cancer patients often undergo surgery followed by adjuvant chemotherapy. However, many of these patients have no benefit from adjuvant chemotherapy and thus receive unnecessary and costly treatment often associated with side-effects. Patients who may benefit from adjuvant chemotherapy can be identified by analyzing the genomic profile of the patients' tumors using a molecular diagnostic test called the 21-gene assay (also known as Oncotype DX assay). However, the budgetary consequences of using Oncotype DX for this purpose in the Netherlands are currently unknown and, therefore, assessed using a health-economic model. The model compared the costs and consequences of using the Oncotype DX assay versus no molecular diagnostic testing and an alternative molecular diagnostic test called MammaPrint. The three diagnostic testing strategies resulted in different costs in terms of several different costing categories and were compared with one another. The total costs were lowest for the diagnostic strategy using the Oncotype DX assay, as it would result in fewer patients receiving adjuvant chemotherapy compared with no molecular diagnostic testing and MammaPrint. Implementing the Oncotype DX assay as a molecular diagnostic test can identify the right patient who benefits from chemotherapy (prevent over- and undertreatment) and lead to cost-savings, reducing the clinical and economic burden on the patient and Dutch healthcare system.

Reevaluating Axillary Lymph Node Dissection in Total Mastectomy for Low Axillary Burden Breast Cancer: Insights from a Meta-Analysis including the SINODAR-ONE Trial.

Complete axillary lymph node dissection (cALND) was previously the standard of care for breast cancer (BC) patients with axillary node disease or macro-metastases found via sentinel lymph node biopsy (SLNB). However, due to significant morbidity, contemporary management now considers a more selective approach, influenced by studies like ACOSOG Z0011. This trial showed that cALND could be omitted without compromising local control or survival in patients with low axillary nodal disease burden undergoing breast-conserving therapy, radiotherapy, and systemic therapy. The relevance of this approach for women with low axillary nodal burden undergoing total mastectomy (TM) remained unclear. A PubMed search up to September 2023 identified 147 relevant studies, with 6 meeting the inclusion criteria, involving 4184 patients with BC and low-volume axillary disease (1-3 positive lymph nodes) undergoing TM. Postmastectomy radiotherapy receipt was similar in both groups. After a mean 7.2-year follow-up, both the pooled results and the meta-analysis revealed no significant differences in overall survival. The combined analysis of the published studies, including the subgroup analysis of the SINODAR-One trial, indicates no survival advantage for cALND over SLNB in T1-T2 breast cancer patients with 1-3 positive sentinel lymph nodes (pN1) undergoing mastectomy. This suggests that, following a multidisciplinary evaluation, cALND can be safely omitted. However, the impact of other patient, tumor, and treatment factors on survival requires consideration and therefore further prospective trials are needed for conclusive validation.

Diagnostic role of F-18 FDG PET/CT in determining preoperative Lymph node status of patients with rectal cancer: a meta-analysis.

PURPOSE: To obtain performance values of PET/CT for determining the nodal status of rectal cancer. MATERIALS: A comprehensive literature search was performed on PubMed and Embase for original diagnostic accuracy studies on the diagnostic performance of PET-CT for detection of LN metastasis in rectal cancer. The QUADAS-2 was used to evaluate the methodological quality of each study. Pooled sensitivity, specificity, and AUC were calculated to estimate the diagnostic role of PET/CT using a random-effects model. A subgroup analysis was performed to investigate the influence of different parameters on diagnostic performance. RESULTS: A total of 15 studies and 1209 patients were included. A publication bias was observed. The pooled sensitivity, specificity, and AUC for PET/CT was 0.62 (95% CI 0.49, 0.74), 0.94 (95% CI 0.87, 0.97), and 0.87 (95% CI 0.83-0.89), respectively. Per-node basis yields higher accuracy than per-patient basis, with pooled sensitivities of 0.65 (95% CI 0.50-0.79) vs. 0.56 (95% CI 0.36-0.77) and specificities of 0.96 (95% CI 0.92-1.00) vs. 0.88 (95% CI 0.76-1.00), but there were no significant differences in diagnostic accuracy. CONCLUSION: PET/CT has high specificity but moderate sensitivity for the detection of LN metastasis in rectal cancer. The current data suggests that the diagnostic capabilities of this method is limited due to its moderate sensitivity.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer.

AIMS: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. MATERIALS AND METHODS: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. RESULTS: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009). CONCLUSION: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Development of a prognostic nomogram for lymph node positive HR+/HER2- breast cancer patients: a study of SEER database and a Chinese cohort.

Background: The hormone receptor+/human epidermal growth factor receptor 2- (HR+/HER2-) breast cancer (BC) patients account for the largest proportion in all patients and are still at high risk of long-range recurrence. This current study aimed to construct a prognostic nomogram to predict 3-year and 5-year BC-specific survival (BCSS) in HR+/HER2- BC patients with axillary lymph node metastasis. Methods: A total of 25,338 HR+/HER2- patients with axillary lymph node-positive BC were enrolled from the Surveillance, Epidemiology and End Results (SEER) database and randomly divided into the training (n=17,738) and validation (n=7,600) cohorts using a ratio of 7:3. Univariate and multivariable Cox regression hazards were used to build a prognostic nomogram based on the training cohort. The nomogram was validated with two independent cohorts. Receiver operating characteristic (ROC) curves and calibration plots were used to evaluate the performance of the model, and Kaplan-Meier survival analyses were applied to test the clinical utility of the risk stratification system. Results: Twelve factors including age, race, marital status, grade, T stage, N stage, radiotherapy, chemotherapy, and metastasis to the bone, brain, lung and liver were identified and incorporated to construct the nomogram (P<0.001). The area under the ROC curve (AUC) values at 3- and 5-year in the training and internal validation sets were 0.800, 0.800, 0.831 and 0.819, respectively, while those of the external set were 0.765 and 0.735, indicating a satisfactory discrimination with our nomogram. The calibration curves showed highly consistent results for the actual and predicted survival probabilities. Furthermore, patients were divided into three risk groups according to the total scores of the nomogram. The risk stratification system accurately differentiated between patients with different BCSS rates. Conclusions: We constructed the first nomogram and corresponding risk stratification system to predict the 3-year and 5-year BCSS for HR+/HER2- patients with lymph node-positive BC, indicating a satisfactory accuracy and clinical application.

The Role of Nodes and Nodal Assessment in Diagnosis, Treatment and Prediction in ER+, Node-Positive Breast Cancer.

The majority of breast cancers are oestrogen receptor-positive (ER+). In ER+ cancers, oestrogen acts as a disease driver, so these tumours are likely to be susceptible to endocrine therapy (ET). ET works by blocking the hormone's synthesis or effect. A significant number of patients diagnosed with breast cancer will have the spread of tumour cells into regional lymph nodes either at the time of diagnosis, or as a recurrence some years later. Patients with node-positive disease have a poorer prognosis and can respond less well to ET. The nodal metastases may be genomically similar or, as is becoming more evident, may differ from the primary tumour. However, nodal metastatic disease is often not assessed, and treatment decisions are almost always based on biomarkers evaluated in the primary tumour. This review will summarise the evidence in the field on ER+, node-positive breast cancer, including diagnosis, treatment, prognosis and predictive tools.

Role of Selective Neck Dissection in Clinically Single Node Positive Disease in Oral Cavity Cancers.

Management of the neck in oral cavity squamous carcinoma is debatable. There is controversy regarding role of SND in single node positive neck in oral SCC. The aim of this study was to determine the efficacy of selective neck dissection (SND) for cN1 neck in patients with oral cancer. A retrospective chart review of 266 oral cancer patients who were clinically single node positive from August 2013 to December 2019 was done. Patients having clinical or radiological cN1 disease undergoing SND were included. Two hundred sixty-six patients were analysed with 86% male predominance. Median age was 48 years. The commonest primary site was Bucco-alveolar complex (64%). Total of 319 SNDs were done in 266 patients. At median follow-up of 29 months, 29 patients (9%) had neck recurrence among which 4 patients had recurrence at level V, along with recurrence at other nodal levels. Three-year regional control was 86%, while DFS and OS were 66% and 68% respectively. For oral cancer with single clinically node positive neck (cN1), SND is an effective and oncological safe treatment. Outcomes are similar with modified neck dissection reported in the literature.

Local Therapy on Clinically Lymph Node-positive Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Patients with clinically lymph node-positive (cN1) prostate cancer (PCa) are traditionally regarded to have metastatic disease, and the role of local therapy (LT) in their treatment remains unclear. OBJECTIVE: To evaluate the outcomes of cN1 PCa patients treated with LT, and secondarily to compare between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). EVIDENCE ACQUISITION: A bibliographic search was performed using Medline, Embase, and the Cochrane Library to identify studies comparing the survival outcomes of cN1 PCa patients treated with LT (RT or RP) with those who did not receive any form of LT (observation or androgen deprivation therapy alone). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations were followed. Survival outcomes of the addition of LT were assessed using a random-effect model. EVIDENCE SYNTHESIS: A total of 8522 patients across eight studies were included. LT significantly improved overall survival (OS) across all time points from 2 to 10 yr compared with patients without LT, most notably providing a durable benefit in 10-yr OS (odds ratio [OR]: 1.49, 95% confidence interval [CI] 1.06-2.10). Both RT and RP were associated with benefits to both OS and recurrence-free survival, with no significant difference in OS between both modalities in medium-term follow-up (4-yr OR: 0.76, 95% CI 0.41-1.40, p = 0.19). CONCLUSIONS: Regardless of modality, the use of LT in cN1 patients improved OS. Future studies should aim to identify patients who could benefit from LT and include more comprehensive survival data including biochemical recurrence. PATIENT SUMMARY: In this study, we evaluated the outcomes of clinically lymph node-positive (cN1) prostate cancer (PCa) patients treated with local therapy (LT) and compared between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). We found that the addition of LT for cN1 PCa patients leads to a significant improvement in survival outcomes, most notably for overall survival, with no significant difference between RT and RP.