Search

Background: This study aims to identify factors predicting recurrence and unfavorable prognosis in cN+ patients who have undergone sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC). Methods: The retrospective multi-centre "MF18-02" and the prospective multi-centre cohort registry trial "MF18-03" (NCT04250129) included patients with cT1-4N1-3M0 with SLNB+/− axillary lymph node dissection (ALND) post-NAC. Results: A total of 2407 cN+ patients, who later achieved cN0 status after NAC and subsequently underwent SLNB, were studied. The majority had cT1-2 (79.1%) and N1 (80.7%). After a median follow-up time of 41 months, the rates of locoregional recurrence and axillary recurrence (AR) were 1.83% and 0.37%, respectively. No significant difference in locoregional recurrence or AR rates was observed between the SLNB/targeted axillary dissection-only (n = 1470) and ALND (n = 937) groups. Factors significantly linked with AR included age younger than 45 years, nonpathological complete response (non-pCR) in the breast, and nonluminal pathology. Locoregional recurrences were associated with nonluminal or HER2(+) pathology, non-pCR in the breast, and ALND. Poor prognostic factors for disease-free survival (DFS) included having cT3-T4, no breast pCR (non-pCR), ypN(+), and nonluminal pathology. No significant difference was found in DFS or disease-specific survival (DSS) rates among ypN0, ypN-isolated tumour cells, ypNmic, and ypN1. However, significant decreases in DFS and DSS rates were observed when comparing ypN2 or ypN3 disease with ypN0. Conclusions: The present large registry data indicate that younger patients (<45), those with nonluminal pathology, and those who only partially respond in the breast are more susceptible to axillary and locoregional recurrences. [ABSTRACT FROM AUTHOR]

Background: The prevention of locoregional recurrence (LRR) is crucial in breast cancer, as it translates directly into reduced breast cancer–related death. Breast cancer is subclassified into distinct intrinsic biological subtypes with varying clinical outcomes. Aims: To perform a systematic review and network meta-analysis (NMA) to determine the rate of LRR by breast cancer molecular subtype. Methods: A NMA was performed as per PRISMA-NMA guidelines. Molecular subtypes were classified by St Gallen expert consensus statement (2013). Analysis was performed using R and Shiny. Results: Five studies were included including 6731 patients whose molecular subtypes were available. Overall, 47.3% (3182/6731) were Luminal A (LABC: estrogen receptor (ER) + /human epidermal growth factor receptor-2 (HER2) − /progesterone receptor (PR) + or Ki-67 < 20%), 25.5% (1719/6731) were Luminal B (LBBC: ER + /HER2 − /PR − or Ki-67 ≥ 20%), 11.2% (753/6731) were Luminal B-HER2 + (LBBC-HER2: ER + /HER2 +), 6.9% (466/6731) were HER2 + (HER2 ER − /HER2 +), and finally 9.1% (611/6731) were triple-negative breast cancer (TNBC: ER − /HER2 −). The median follow-up was 74.0 months and the overall LRR rate was 4.0% (271/6731). The LRR was 1.7% for LABC (55/3182), 5.1% for LBBC (88/1719), 6.0% for LBBC-HER2 (45/753), 6.0% for HER2 (28/466), and 7.9% for TNBC (48/611). At NMA, patients with TNBC (odds ratio (OR) 3.73, 95% confidence interval (CI) 1.80–7.74), HER2 (OR 3.24, 95% CI 1.50–6.99), LBBC-HER2 (OR 2.38, 95% CI 1.09–5.20), and LBBC (OR 2.20, 95% CI 1.07–4.50) were significantly more likely to develop LRR compared to LABC. Conclusion: TNBC and HER2 subtypes are associated with the highest risk of LRR. Multidisciplinary team discussions should consider these findings to optimize locoregional control following breast cancer surgery. [ABSTRACT FROM AUTHOR]

PD-L1 is a glycoprotein present on antigen-presenting cells and malignant cells and activates the PD-L1 receptor on cells surfaces, leading to T-cell anergy and death. The objective of this study was to assess PD-L1 tumoral expression in 50 patients with oral squamous cell carcinoma, define its prognostic value, and investigate its association with 2-year overall survival, locoregional recurrence, distant metastasis, and a number of other clinicopathological parameters. In a 24-month prospective observational study, involving 50 oral cavity squamous cell carcinoma patients, PD-L1 tumoral expression was evaluated using semiquantitative immunohistochemistry analysis by an experienced pathologist. PD-L1 expression of ≥ 6% of tumor cells was associated with poor survival outcome and determined to be a pertinent clinical cutoff value. PD-L1 expression of ≥ 6% was significantly associated with a number of clinicopathological parameters in our study of 50 patients with OSCC. Pathological nodal staging (P = 0.00), lympho-vascular invasion (P = 0.03), extra-nodal extension (P = 0.04), overall staging (P = 0.01), locoregional recurrence (P = 0.00), and distant metastasis (P = 0.00) all showed statistically significant associations. Our study concluded a significant correlation with decreased 2-year overall survival and 2-year disease free survival by using the Kaplan- Meier survival plot for overall survival (p = 0.02) and (p = 0.0002), respectively. The presence of ≥ 6% PD-L1 (CD274) tumoral expression was found to be significantly associated with 2-year overall survival (OS), locoregional recurrence (LRC), distant metastasis (DM), and various clinicopathological parameters. Tumoral PD-L1 was found as a discrete prognostic biomarker which showed significant association with tumor aggressiveness. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the impact of periodic neck ultrasonography (US) on postoperative surveillance for locoregional disease control of patients with low- and intermediate-risk papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. This retrospective cohort study included patients with PTC who underwent total thyroidectomy and central neck dissection at our institution between January, 2000 and December, 2016. The patients were divided into two groups: the physical examination (PE) group (follow-up by PE without periodic US) and the US group (follow-up by PE with periodic US). Serum thyroglobulin levels were measured periodically in both groups. Propensity score matching was used to rigorously balance the significant variables and assess the 10-year postoperative outcomes between the groups. Of the 189 patients, 150 were included after matching (75 in each group). There were no significant differences between the two groups in terms of background characteristics. The median follow-up period was 127.9 months. There was no significant difference in locoregional relapse-free survival between the PE and US groups (97.0 vs. 98.7%, p = 0.541). The overall survival was 96.7% and 98.7% in the PE and US groups, respectively, with no significant difference (p = 0.364). This study demonstrated that the addition of periodic US to PE for postoperative surveillance of patients with low- and intermediate-risk PTC who underwent total thyroidectomy did not significantly affect locoregional control.

Objectives: To evaluate the agreement among radiologists in the evaluation of rectal cancer staging and restaging (after neoadjuvant therapy) and assess whether locoregional recurrence can be predicted with this information. Materials and Methods: Pre-neoadjuvant and after-neoadjuvant therapy magnetic resonance imaging (MRI) examinations of 239 patients diagnosed with locally advanced rectal cancer were retrospectively reviewed by three radiologists. The agreement between the MRI findings (localization of tumor involvement, tumor coverage pattern, external sphincter involvement, mucin content of the mass and lymph node, changes in the peritoneum, MRI T stage, distance between tumor and MRF, submucosal sign, classification of locoregional lymph node, and EMVI) was discussed at the September 2023 meeting of the Society of Abdominal Radiology (SAR) and the interobserver and histopathological findings were examined. The patients were evaluated according to locoregional rectal cancer and lateral lymph node (LLN) staging, and re-staging was performed using MRI images after neoadjuvant treatment. The ability of the locoregional and LLN staging system to predict locoregional recurrence was evaluated. Results: Among the parameters examined, for the MRI T stage and distance between the tumor and the MRF, a moderate agreement (kappa values: 0.61–0.80) was obtained, while for all other parameters, the interobserver agreement was notably high (kappa values 0.81–1.00). LLNs during the restaging with an OR of 2.1 (95% CI = 0.33–4.87, p = 0.004) and a distance between the tumor and the MRF of less than 1 mm with an OR of 2.1 (95% CI = 1.12–3.94, p = 0.023) affected locoregional recurrence. A multivariable Cox regression test revealed that the restaging of lymph nodes among the relevant parameters had an impact on locoregional recurrence, with an OR of 1.6 (95% CI = 0.32–1.82, p = 0.047). With the LLN staging system, an increase in stage was observed in 37 patients (15.5%), and locoregional recurrence was detected in 33 of them (89.2%) (p < 0.001). Conclusions: LLN staging is not only successful in predicting locoregional recurrence among MRI parameters but is also associated with a very high level of interobserver agreement. The presence of positive LLN in the restaging phase is one of the most valuable MRI parameters for poor prognosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. Methods: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. Results: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829–0.958) for the training cohort and 0.944 (0.849–1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. Conclusions: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice. [ABSTRACT FROM AUTHOR]

Locoregional recurrence of non–small‐cell lung cancer (NSCLC) after complete resection lacks standard treatment. Durvalumab after chemoradiotherapy (CRT) or CRT alone is often selected in daily clinical practice for patients with locoregional recurrence; however, the therapeutic efficacy of these treatments remains unclear, and we aimed to assess this. This retrospective observational study used data from patients with NSCLC diagnosed with locoregional recurrence after complete resection who subsequently underwent concurrent CRT followed by durvalumab (CRT‐D group) or CRT alone (CRT group). We employed propensity score analysis with inverse probability treatment weighting (IPTW) to adjust for various confounders and evaluate efficacy in the CRT‐D group. After IPTW adjustment, the CRT‐D group contained 119 patients (64.7% male; 69.7% adenocarcinoma), and the CRT group contained 111 patients (60.5% male; 73.4% adenocarcinoma). Their mean ages were 66 and 65 years, respectively. The IPTW‐adjusted median progression‐free survival was 25.4 and 11.5 months for the CRT‐D and CRT groups, respectively (hazard ratio, 0.44; 95% confidence interval, 0.30–0.64); the median overall survival was not reached in either group favoring CRT‐D (hazard ratio, 0.49; 95% confidence interval, 0.24–0.99). Grade 3 or 4 adverse events were observed in 48.8% of patients during CRT, 10.7% after initiating durvalumab maintenance therapy in the CRT‐D group, and 57.3% in the CRT group. Overall, the sequential approach of CRT followed by durvalumab is a promising treatment strategy for locoregional recurrence of NSCLC after complete resection. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions In this study, we aimed to assess the effect of prophylactic central compartment neck dissection (pCCND) in conjunction with hemithyroidectomy (HT) for clinically low‐risk node‐negative (cN0) papillary thyroid carcinoma (PTC).A thorough literature search was performed utilizing PubMed and EMBASE for articles published until October 2023. Subsequently, a meta‐analysis was performed on studies involving patients with cN0 PTC, with postoperative locoregional recurrence (LRR) and survival data, treated with HT + pCCND or HT. The study was registered with PROSPERO (CRD42024560962).We included seven studies in this meta‐analysis, including 2132 patients who met the inclusion criteria: six retrospective cohort studies and one randomized controlled trial. The HT + pCCND group consisted of 1090 cases, and the HT group had 1042 cases. The LRR rates after HT with or without pCCND were similar (3.58% vs. 4.51%; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.41–1.03). Five of the seven studies provided prognostic and survival data, particularly the log hazard ratio (log HR) of disease‐free survival (DFS) between the two groups. There was also no significant difference in terms of DFS between the HT + pCCND and HT groups (OR = 0.67; 95% CI = 0.42–1.07).There was no significant difference in LRR and DFS between the HT + pCCND and HT groups. pCCND did not demonstrate significant efficacy in improving oncological outcomes for low‐risk patients with cN0 PTC. Therefore, for patients with low‐risk cN0 PTC, thyroid surgeons should make reasonable and individualized decisions regarding the extent of surgical removal. [ABSTRACT FROM AUTHOR]

Purpose: The survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database. Methods: Patients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined. Results: A total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis. Conclusions: Based on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy (dCRT) is a potentially curative therapy for esophageal cancer. As indications for dCRT differ widely, it is challenging to draw conclusions on outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns according to indications for treatment. Patients who underwent dCRT (50.4 Gy concomitant with carboplatin/paclitaxel) for esophageal cancer between 2012 and 2022 were identified. Indications for dCRT were: cervical tumor, irresectable disease, unfit for surgery, and patient and/or physician preference. The primary endpoint was OS calculated with the Kaplan–Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality, and disease recurrence. One hundred and fifty-seven patients were included (72.6% esophageal squamous cell carcinoma) with a median follow-up of 20 months (IQR 10.0–43.9). The full dCRT regimen was completed by 116 patients (73.9%). Thirty- and 90-day mortality were 2.5% and 8.3%, respectively. Median and 5-year OS for all patients were 22.9 months (95% CI 18.0–27.9) and 31.4%, respectively. The median OS per indication was 23.7 months (95% CI 6.5–40.8) for patients with cervical tumors, 10.9 months (95% 0.0–23.2) for irresectable disease, 28.2 months (95% CI 12.3–44.0) for unfit patients, and 22.9 months (95% CI 15.4–30.5) for patients' preference for dCRT (P  = 0.11). Disease recurrence was observed in 74 patients (46%), located locoregionally (46%), distant (19%), or combined (35%). Patients who underwent dCRT had a 5-year OS of 31.4%, but OS differed according to indications for treatment with patients who had irresectable disease having the worst prognosis. [ABSTRACT FROM AUTHOR]

Background: The Nottingham prognostic index (NPI) has been shown to negatively impact survival in breast cancer (BC). However, its ability to predict the locoregional recurrence (LRR) of BC remains still unclear. This study aims to determine whether a higher NPI serves as a significant predictor of LRR in BC. Methods: In total, 238 patients with BC were included in this analysis, and relevant clinicopathological features were collected. Correlation analysis was performed between NPI scores and clinicopathological characteristics. The optimal nomogram model was determined by Akaike information criterion. The accuracy of the model's predictions was evaluated using receiver operating characteristic curves (ROC curves), calibration curves and goodness of fit tests. The clinical application value was assessed through decision curve analysis. Results: Six significant variables were identified, including age, body mass index (BMI), TNM stage, NPI, vascular invasion, perineural invasion (P<0.05). Two prediction models, namely a TNM-stage-based model and an NPI-based model, were constructed. The area under the curve (AUC) for the TNM-stageand NPI-based models were 0.843 (0.785,0.901) and 0.830 (0.766,0.893) in training set and 0.649 (0.520,0.778) and 0.728 (0.610,0.846) in validation set, respectively. Both models exhibited good calibration and goodness of fit. The Fmeasures were 0.761vs 0.756 and 0.556 vs 0.696, respectively. Clinical decision curve analysis showed that both models provided clinical benefits in evaluating risk judgments based on the nomogram model. Conclusions: a higher NPI is an independent risk factor for predicting LRR in BC. The nomogram model based on NPI demonstrates good discrimination and calibration, offering potential clinical benefits. Therefore, it merits widespread adoption and application. [ABSTRACT FROM AUTHOR]

Introduction: The routine assessment of intraoperative margins has long been the standard of care for oral cavity cancers. However, there is a controversy surrounding the best method for sampling surgical margins. The aim of our study is to determine the precision of a new technique for sampling tumor bed margins (TBMs), to evaluate the impact on survival and the rate of free flap reconstructions. Methods: This retrospective cohort study involved 156 patients with primary cancer of the tongue or floor of the mouth who underwent surgery as initial curative treatment. Patients were separated into 2 groups: one using an oriented TBM derived from Mohs' technique, where the margins are taken from the tumor bed and identified with Vicryl sutures on both the specimen and the tumor bed, and the other using a specimen margins (SMs) driven technique, where the margins are taken from the specimen after the initial resection. Clinicopathologic features, including margin status, were compared for both groups and correlated with locoregional control. Precision of per-operative TBM sampling method was obtained. Results: A total of 156 patients were included in the study, of which 80 were in TBM group and 76 were in SM group. Precision analysis showed that the oriented TBM technique pertained a 50% sensitivity, 96.6% specificity, 80% positive predictive value, and an 87.5% negative predictive value. Survival analysis revealed nonstatistically significant differences in both local control (86.88% vs 83.50%; P =.81) as well as local-regional control (82.57% vs 72.32%; P =.21). There was a significant difference in the rate of free flap-surgeries between the 2 groups (30% vs 64.5%; P <.001). Conclusion: Our described oriented TBM technique has demonstrated reduced risk of free flap reconstructive surgery, increased precision, and similar prognostic in terms of local control, locoregional control, and disease-free survival when compared to the SM method. [ABSTRACT FROM AUTHOR]

Background: The American Thyroid Association guidelines primarily recommend central neck dissection for papillary thyroid carcinoma with advanced primary tumors or clinically positive neck nodes. However, the appropriate extent of dissection remains unclear. We aimed to compare the rate of locoregional recurrence between unilateral and bilateral central neck dissection in invasive papillary thyroid carcinoma. Methods: Among 330 consecutive patients who underwent total thyroidectomy with central neck dissection for advanced papillary thyroid carcinoma, 212 underwent unilateral central neck dissection (UCND group) while 118 underwent bilateral central neck dissection (BCND group). We performed 1:1 propensity score matching, resulting in 99 matched pairs. Surgical outcomes and safety were compared between the two groups. Additionally, the impact of surgery on locoregional recurrence was compared using survival analysis. Results: During a follow‐up of 47.8 ± 20.4 months, 29 (8.8%) patients experienced locoregional recurrence within the entire study cohort. Following propensity score matching, no significant difference in recurrence‐free survival was observed between the two groups (log‐rank p = 0.516). Multivariate analysis revealed that only T4 staging was an independent risk factor for locoregional recurrence (p = 0.006). The mean number of total and metastatic central lymph nodes retrieved were significantly greater in BCND group (14.1 vs. 9.3, p < 0.001 and 6.8 vs. 4.6, p = 0.005, respectively). There was no significant difference in postoperative stimulated thyroglobulin levels between the two groups (0.79 ng/mL vs. 1.44 ng/mL, p = 0.389). Conclusion: The present study demonstrates no prognostic benefit in conducting bilateral central neck dissection. Unilateral central neck dissection may be the preferred choice for clinically invasive papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the patterns of recurrence and their associated risk factors in patients who underwent resection for pancreatic carcinoma. This retrospective study included 272 patients, who underwent Ro/R1-resection of PDAC from 2005 to 2020 at the University Hospital Erlangen. Risk factors for different recurrence patterns and the prognostic value of recurrence pattern on the overall survival after recurrence were evaluated. 61 % of the patients experienced recurrence, mostly within the first 12 postoperative months (62 %) and in the form of metastases (87 %). The median overall survival from recurrence was 9.2 months. The preoperative absence of diabetes and the presence of lymph node metastasis were independent risk factors for recurrence and a preoperative CA19-9 exceeding 97 U/ml for early recurrence. Additionally, lymph node metastases were associated with a higher risk of metastatic recurrence. Early recurrence, but not the site of recurrence, was identified as an independent prognostic factor for worse overall survival from recurrence. The occurrence of recurrence and especially of early and metastatic recurrence are associated with a worse overall survival. Patients lacking preoperative diabetes, having high preoperative CA19-9 values and lymph node metastases are particularly at risk for (early) recurrence. [ABSTRACT FROM AUTHOR]

Background: Individual risk prediction of 5-year locoregional recurrence (LRR) and contralateral breast cancer (CBC) supports decisions regarding personalised surveillance. The previously developed INFLUENCE tool was rebuild, including a recent population and patients who received neoadjuvant systemic therapy (NST). Methods: Women, surgically treated for nonmetastatic breast cancer, diagnosed between 2012 and 2016, were selected from the Netherlands Cancer Registry. Cox regression with restricted cubic splines was compared to Random Survival Forest (RSF) to predict five-year LRR and CBC risks. Separate models were developed for NST patients. Discrimination and calibration were assessed by 100x bootstrap resampling. Results: In the non-NST and NST group, 49,631 and 10,154 patients were included, respectively. Age, mode of detection, histology, sublocalisation, grade, pT, pN, hormonal receptor status ± endocrine treatment, HER2 status ± targeted treatment, surgery ± immediate reconstruction ± radiation therapy, and chemotherapy were significant predictors for LRR and/or CBC in non-NST patients. For NST patients this was similar, but excluding (y)pT and (y)pN status, and including presence of ductal carcinoma in situ, axillary lymph node dissection and pathologic complete response.For non-NST patients, the Cox and RSF models were integrated in the online tool with 5-year AUCs of 0.77 (95%CI:0.77–0.77) and 0.68 (95%CI:0.67–0.68)] for LRR and CBC prediction, respectively. For NST patients, the RSF model performed best (AUCs 0.77 (95%CI:0.76–0.78) and 0.73 (95%CI:0.69–0.76) for LRR and CBC, respectively). Regarding calibration, observed-predicted differences were all

Background: Neoadjuvant chemotherapy (NACT) for early-stage breast cancer is associated with an increased risk of locoregional recurrence (LRR). We investigated whether the risk of LRR after NACT varies across tumor subtypes. Methods: We retrospectively reviewed the medical records of women who underwent breast-conserving surgery for breast cancer at three institutions between January 1, 2004, and December 31, 2018. Patients received either NACT or adjuvant chemotherapy (ACT), followed by radiotherapy. LRR was analyzed according to the hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status using propensity score matching, log-rank test, and Cox regression analysis. Results: Among 10,328 patients, 2479 (24.0 %) received NACT. Within the median follow-up of 84.5 (IQR, 35.1–118.5) months, the 10-year LRR-free survival rates were 94.5 % and 90.7 % for the ACT and NACT groups, respectively (hazard ratio: 2.04, 95 % confidence interval [CI]: 1.68–2.46, p

Background: Despite stage IV categorization, survival outcomes for breast cancer patients who experience contralateral axillary lymph node metastasis (CAM) remain uncertain. This study aimed to investigate the clinical outcomes for patients with metachronous CAM to provide insights into its prognosis and treatment recommendations. Methods: This study retrospectively reviewed medical records of patients who underwent curative surgery for breast cancer and experienced CAM as the first site of distant metastasis (DM) during the follow-up period between January 2001 and April 2023. Survival outcomes of the CAM patients were compared with those of breast cancer patients with other DM via propensity score-matching (PSM). Results: The study identified 40 breast cancer patients with metachronous CAM. The estimated 5-year overall survival (OS) was 39.6%, and the progression-free survival was 39.4%. The patients with CAM exhibited marginally better OS than the patients with DM (p = 0.071), but survival similar to that of the patients with isolated supraclavicular node recurrence (SCN) (p = 0.509). Moreover, matching of CAM with DM using two PSM models showed a consistently insignificant survival difference (hazard ratio [HR], 1.47; p = 0.124 vs. HR, 1.19; p = 0.542). Ipsilateral breast tumor recurrences (IBTRs) were experienced by 12 patients before or concurrently with the CAM. These patients exhibited significantly better survival than the remaining patients (HR, 0.28; p = 0.024). Conclusion: The breast cancer patients with CAM showed survival similar to that for the patients with DM, supporting the current stage IV classification of the CAM. However, CAM associated with IBTR exhibited superior survival outcomes, suggesting that this subset of CAM may benefit from treatments with curative intent. [ABSTRACT FROM AUTHOR]

Abstract Preclinical studies suggest that loss of LKB1 expression renders cancer cells less responsive to radiation partly through NRF2-mediated upregulation of antioxidant enzymes protecting against radiation-induced DNA damage. Here we investigated the association of an alteration in this pathway with radio-resistance in lung cancer patients. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who were treated with chemoradiotherapy (CRT) and analyzed for LKB1 expression using semiquantitative immunohistochemistry. Clinical characteristics and expression of LKB1 were analyzed for association with radiotherapy outcomes. We analyzed 74 available tumor specimens from 178 patients. After a median follow-up of 40.7 months, 2-year cumulative incidence of locoregional recurrence (LRR) in patients who had LKB1Low expression was significantly higher than those with LKB1High expression (68.8% vs. 31.3%, P = 0.0001). LKB1Low expression was found significantly associated with a higher incidence of distant metastases (DM) (P = 0.0008), shorter disease-free survival (DFS) (P = 0.006), and worse overall survival (OS) (P = 0.02) compared to LKB1High expression. Moreover, patients with LKB1Low expression showed a significantly higher 2-year cumulative incidence of LRR (77.6% vs. 21%; P = 0.02), higher DM recurrence (P = 0.002), and shorter OS (P

Background: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. Methods: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. Results: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74–1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. Conclusion: IBR after NAC is a safe procedure with an acceptable postoperative complication profile. [ABSTRACT FROM AUTHOR]

Preclinical studies suggest that loss of LKB1 expression renders cancer cells less responsive to radiation partly through NRF2-mediated upregulation of antioxidant enzymes protecting against radiation-induced DNA damage. Here we investigated the association of an alteration in this pathway with radio-resistance in lung cancer patients. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who were treated with chemoradiotherapy (CRT) and analyzed for LKB1 expression using semiquantitative immunohistochemistry. Clinical characteristics and expression of LKB1 were analyzed for association with radiotherapy outcomes. We analyzed 74 available tumor specimens from 178 patients. After a median follow-up of 40.7 months, 2-year cumulative incidence of locoregional recurrence (LRR) in patients who had LKB1Low expression was significantly higher than those with LKB1High expression (68.8% vs. 31.3%, P = 0.0001). LKB1Low expression was found significantly associated with a higher incidence of distant metastases (DM) (P = 0.0008), shorter disease-free survival (DFS) (P = 0.006), and worse overall survival (OS) (P = 0.02) compared to LKB1High expression. Moreover, patients with LKB1Low expression showed a significantly higher 2-year cumulative incidence of LRR (77.6% vs. 21%; P = 0.02), higher DM recurrence (P = 0.002), and shorter OS (P < 0.0001) compared with the EGFR-mutant group. For all patients with LKB1Low who had LRR, these recurrences occurred within the field of radiation, in contrast to those with LKB1High expression having both in-field, marginal, and out-of-field failures. LKB1 expression may serve as a potential biomarker for poor outcomes after receiving radiation in LA-NSCLC patients. Further studies to confirm the association and application are warranted. [ABSTRACT FROM AUTHOR]

Objective: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. Results: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ ∑ D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ ∑ D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. Conclusions: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re‑irradiation with IMRT and we propose a EQD2_ ∑ D80 threshold of 137.035 Gy for the nasopharynx. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). METHODS We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan–Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine–Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. RESULTS Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P  <   0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22–0.80; subdistribution HR = 0.43; 95% confidence interval 0.23–0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43–1.00) after complete versus incomplete anatomic segmentectomy. CONCLUSIONS This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible. [ABSTRACT FROM AUTHOR]

Recently published large multicenter prospective clinical trials have demonstrated that sublobar resection is noninferior to lobectomy, the traditional treatment of choice, for peripherally located early-stage lung cancer. Most clinical trials and several retrospective studies published to date have used the consolidation-to-tumor ratio to define the indication for sublobar resection, as it is well known that the size of the solid portion seen on high-resolution computed tomography is highly correlated with pathologic invasiveness. However, it is difficult to accurately predict pathologic features that may increase the risk of locoregional recurrence, such as specific adenocarcinoma subtypes or spread through air spaces, based on imaging characteristics alone, and the location of the nodule also should be considered one of the important factors in obtaining an adequate parenchymal resection margin. In this article, we summarize the results of the most recently published clinical trials related to sublobar resection and discuss various factors that should be considered for optimal candidate selection for sublobar resection.

Simple Summary: Ductal carcinoma in situ is a malignant cell proliferation confined to basement membrane. Current consensus guidelines recommend an optimal margin width of 2 mm and re-excision for closer margin is debated and it is sent back to clinical judgment. Our retrospective study evaluating 197 patients aim to investigate the importance of surgical margin and locoregional recurrence in patients with diagnosis of DCIS and treated with conservative breast surgery. We found no correlation between margins and loco-regional recurrence, and re-excision should be avoided in patients with focally positive margin and no evidence of the disease at post-surgical imaging. The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging. [ABSTRACT FROM AUTHOR]

The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. To develop time-to-event risk prediction models for melanoma metastatic recurrence. Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P <.001) and to locoregional recurrences only (HR: 5.79, P <.001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. Retrospective nature and cohort from one geography. These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) grows slowly and is characterised by potential recurrence and metastasis to distant organs. This study aimed to evaluate the risk factors for locoregional recurrence (LRR) and distant metastasis in patients with ACC of the external auditory canal (EAC). Demographic, pathological, therapeutic and survival data of 143 patients with EAC ACC were reviewed in this study. Univariate and multivariate Cox proportional hazard regression analyses were carried out to determine the risk factors for LRR and distant metastasis. Factors associated with overall survival after LRR and distant metastasis were also analysed. During a median follow-up of 49 months, 31 of 143 patients were observed with LRR and 34 developed distant metastasis. Bone invasion and histological subtype were independent risk factors for locoregional recurrence-free survival. T stage and LRR were independent risk factors for distant metastasis-free survival. Salvage surgery and adjuvant radiotherapy or chemoradiotherapy for LRR resulted in better survival, whereas extrapulmonary metastasis and LRR were associated with a higher risk of poor survival after distant metastasis. Patients with distant metastases, especially those with LRR, are at significant risk of poor prognosis. Our findings emphasise the importance of long-term regular follow-up and recommend surgical intervention with radiotherapy for recurrent EAC ACC. • Largest series of adenoid cystic carcinoma of the external auditory canal from a single centre. • Identify the risk factors influencing survival after the occurrence of locoregional recurrence and distant metastasis. • Emphasise the importance of long-term regular follow-up. • Provide guidance for treating physicians in terms of risk stratification and treatment strategies. [ABSTRACT FROM AUTHOR]

Aims: To compare healthcare resource utilization (HRU) and costs between patients with or without melanoma recurrence and between patients with distant or locoregional melanoma recurrence. Methods: Patients aged ≥65 years with completely resected, stage IIB/IIC or III melanoma were identified from Surveillance, Epidemiology, and End Results-Medicare data and stratified based on whether they experienced a recurrence, and whether it was distant or locoregional (separately for each stage). The index date was the date of recurrence (recurrence group) or a randomly assigned date (non-recurrence group). Patients in the recurrence and non-recurrence groups were propensity score-matched 1:1 based on patient characteristics; HRU and healthcare costs were compared between the 2 groups and between patients with distant or locoregional recurrence during the ≤24 months following index. Results: After matching, 507 pairs of patients with recurrent or non-recurrent stage IIB/IIC melanoma (236 patients with distant recurrence, 271 with locoregional) and 141 pairs of patients with recurrent or non-recurrent stage III melanoma (50 patients with distant recurrence, 91 with locoregional) were included. During the first year following recurrence, unadjusted HRU was generally higher in patients with versus without recurrence and patients with distant versus locoregional recurrence among both stage IIB/IIC and III cohorts. Patients who experienced recurrence incurred $6,474 (stage IIB/IIC) or $6,112 (stage III) per patient per month (PPPM) more in unadjusted, all-cause, total healthcare costs than patients without recurrence (both p < 0.001). Patients with distant recurrence incurred $7,292 (stage IIB/IIC) or $5,436 (stage III) PPPM more in unadjusted, all-cause, total healthcare costs than patients with locoregional recurrence (both p < 0.05). Limitations: Melanoma recurrence was identified using a claims-based algorithm. Conclusions: Economic burden is higher in patients with versus without melanoma recurrence and patients with distant versus locoregional recurrence. There is a high unmet need for adjuvant therapies that may help to prevent or delay recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: Historically, patients undergoing complete lymphadenectomy (CLD) for clinically evident nodal disease were candidates to receive adjuvant radiotherapy (RT), with the goal of reducing the risk of lymph node basin (LNB) relapse. However, most recent systemic therapy (ST) trials investigating adjuvant immune checkpoint inhibitors and targeted therapies have excluded patients who had received adjuvant RT prior to ST. Therefore, the role of this therapy is under-investigated, and patients who may have previously received adjuvant RT may now be receiving adjuvant ST and forgoing adjuvant RT. We observed that there was a significant shift away from the use of radiotherapy toward systemic therapies after 2015 compared to before 2015 in a population that met indications for radiotherapy. We further found that the LNB recurrence rate was similar between those treated with adjuvant RT and ST, and ST was associated with a reduced incidence of any recurrence or progression compared to adjuvant RT. Modern adjuvant systemic therapies (STs) have revolutionized the management of stage III melanoma. Currently, the role of adjuvant radiotherapy (RT) remains unclear. In this single-center retrospective study, patients with clinically detectable stage III melanoma with high-risk features for lymph node basin (LNB) recurrence and whose tumors were fully resected with complete lymphadenectomy (CLD) between 2010 and 2019 were assessed. We determined the cumulative incidence (CIF) of LNB recurrence and any disease recurrence or progression using competing risk analysis. A total of 108 patients were identified; the median age was 59 years (24–92), and 74 (69%) were men. A total of 51 (42%) received adjuvant RT, 22 (20%) received adjuvant ST, and 35 (32%) received no adjuvant therapy. The advent of ST changed clinical practice, with a significant increase in the use of adjuvant ST and a decrease in the use of RT when comparing practice patterns before and after 2015 (p < 0.001). The 3-year CIF of LNB recurrence was similar in patients treated with adjuvant RT (6.3%) and adjuvant ST (9.8%). The 3-year CIF of any disease recurrence or progression was lower in patients receiving adjuvant ST (24%) compared to those receiving adjuvant RT (52%) or no adjuvant therapy (55%, p = 0.06). Three-year overall survival (OS) was not significantly different in patients treated with ST compared to those not treated with any ST (p = 0.118). Despite ST replacing RT as the dominant adjuvant treatment modality, this change in practice has not resulted in increased LNB recurrence for patients at high risk of LNB recurrence following CLD. [ABSTRACT FROM AUTHOR]

Simple Summary: Plasma Epstein–Barr virus (EBV) DNA is an important prognostic marker for nasopharyngeal carcinoma (NPC). However, EBV DNA is less sensitive to locoregional recurrence compared to distant metastasis in NPC. Numerous findings suggest that the presence of tumour-infiltrating lymphocytes (TILs) is associated with NPC prognosis. Nevertheless, NPC is characterised by the presence of abundant TILs. This study aims to generate TIL scores in NPC from H&E-stained tissue slide images for NPC prognosis. We employed artificial intelligence and deep learning-based method for generating TIL score. Our results indicate that our methods have strong prognostic value compared to the EBV DNA copies in locoregional recurrence cases. Background: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein–Barr virus DNA, are not sensitive to locoregional recurrence. Methods: We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. Results: Based on Kaplan–Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13–2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11–2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. Conclusion: The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC. [ABSTRACT FROM AUTHOR]

Tongue defects following resection of cancers, have a major effect on speech and swallowing, impairing the quality of life. Free flaps such as the free radial artery forearm flap and anterolateral thigh flap have been ideal for the reconstruction of such defects depending upon the volume of tissue loss. Local flaps such as the submental flap and pectoralis major myocutaneous flap serve as an alternative in decreasing morbidity and improving functional outcomes. Surgical outcomes associated with submental flaps used in the reconstruction of tongue defects were evaluated in our study. This is a retrospective analysis of 545 patients, where the submental flap was used for the repair of tongue defects for cancer resections. Oncological safety was studied in 375 patients with a median follow-up of 48 months. 140 patients were studied for their functional outcomes using the parameters, adapted from the University of Washington- Quality of Life questionnaire. Complete flap loss was seen in 15(2.75%) patients while 22(4.03%) patients had partial loss of flap. Locoregional Recurrences, second primary, and distant metastases were noted in 91 of the 375 patients studied. The mean score for swallowing, speech, and taste were 72,71, and 69 respectively. The submental flap is an effective and reliable alternative for the reconstruction of tongue defects. [ABSTRACT FROM AUTHOR]

Background: There are limited data examining racial disparities in locoregional recurrence (LRR) among women with access to high-quality care. We aimed to examine differences in late LRR by race in patients with stage I–IIIA, hormone receptor-positive (HR+) breast cancer enrolled in the National Surgical Adjuvant Breast and Bowel (NSABP) B-42 trial. Methods: From 2006 to 2010, 3966 postmenopausal women with stage I–IIIA HR+ breast cancer who were disease-free after 5 years of endocrine therapy were randomized to an additional 5 years of endocrine therapy or placebo. Patients were excluded if multi-racial or if race was unknown. Kaplan–Meier curves were used to estimate 6-year LRR from the time of trial registration and according to race. Cox proportional hazards models were used for adjusted survival analyses. Results: Overall, 3929 NSABP B-42 patients were included: 3688 (93.9%) White, 151 (3.8%) Black, and 90 (2.3%) Asian patients. Median follow-up was 75.2 months. Overall estimated 6-year LRR from trial registration was 1.8% and differed by race: LRR rates were 1.7% in White women, 4.9% in Black women, and 0% in Asian women (p = 0.046). Adjusted Cox proportional hazards analysis found Black race to be independently associated with LRR (hazard ratio [HzR] 2.36, 95% confidence interval [CI] 1.01–5.49; p = 0.047). Node-positivity was also associated with increased LRR (HzR 1.75, 95% CI 1.07–2.86; p = 0.025). Adjusted Cox analysis found LRR (HzR 2.32, 95% CI 1.33–4.06; p = 0.003) to be associated with increased overall mortality; however, race was not independently associated with mortality. Conclusion: Among postmenopausal patients with stage I–IIIA HR+ breast cancer in the NSABP B-42 trial, racial differences in late LRR were present, with the highest LRR in Black women. [ABSTRACT FROM AUTHOR]

Purpose: Locoregional recurrence of esophageal carcinoma after neoadjuvant therapy and en bloc esophagectomy, although uncommon, is challenging to manage. Currently, there are no standard treatment approaches prompting many health care providers to adopt a palliative approach. We describe our experience and outcomes of treating this specific group of patients with a focus on salvage curative intent local therapy. Methods: All patients undergoing en bloc esophagectomy following neoadjuvant therapy between 2007 and 2017 at the McGill University Health Centre, a tertiary referral center for esophageal cancer, were identified. Patient follow-up included a structured surveillance protocol with serial endoscopic and cross-sectional imaging studies. Local recurrence was defined as histologically confirmed recurrences at the anastomosis. Regional recurrence was defined as radiological evidence of celiac, mediastinal, or para-esophageal/conduit lymphadenopathy. Demographic, pathologic, therapeutic variables were extracted as well as disease free and overall survival. Results: Of 755 patients identified, locoregional recurrences occurred in 27 patients (3.6%) of whom 18 were included in the analysis. The median disease-free survival post index operation was 15 months (IQR 10–23). The sites of recurrence were local (6/18, 33.3%); regional (8/18, 44.4%); and locoregional (4, 22.2%). Chemoradiation was the most common modality used to treat recurrence (10/18, 55.6%) whilst 4 (22.2%) underwent surgery. Following treatment for locoregional recurrence, 1-year overall survival was 61.1% and at 5 years was 22.2%. Conclusion: Consolidative salvage local therapy for locoregional recurrence after en bloc esophagectomy is feasible and can entail prolonged survival in a subset of patients. [ABSTRACT FROM AUTHOR]

Abstract Objective Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity. Methods We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo‐radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab. Results Patients with HPV‐associated tumors and nonsmokers demonstrated improved overall and disease‐free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen. Conclusions Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. Level of Evidence 4.

Abstract Background Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non‐small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. Methods A total of 118 patients who underwent tumor resection with mutation‐detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Results Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3‐year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR‐free survival as compared to patients with wild‐type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Conclusions Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Background: Contralateral axillary lymph node metastasis (CAM) is rare. It remains controversial whether CAM should be regarded as a regional or distant metastatic disease. Our study aims to investigate the accurate clinical orientation and management of CAM. Methods: Two hundred and ninety-nine female patients diagnosed with breast cancer from 2000 to 2014 and confirmed to develop CAM, oligometastasis (OM) or locoregional recurrence (LRR) at Fudan University Shanghai Cancer Center (FUSCC) were included in this study. Baseline information and survival outcomes were analyzed and compared among the three groups. Results: Patients with CAM exhibited similar overall survival (OS) and progression-free survival (PFS) to those with OM, but worse than those with LRR (HR: 0.47 [95 % CI: 0.27–0.85], p = 0.0097; HR:0.39 [95 % CI: 0.24–0.63], p

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a locoregional therapy that may be combined with cytoreductive surgery (CRS) to treat patients with colorectal cancer and peritoneal metastases (PM). In recent years, three randomized controlled trials (RCTs) have investigated the role of prophylactic or adjuvant HIPEC in preventing the development of PM in patients with high-risk colorectal cancer: PROPHYLOCHIP and COLOPEC evaluated adjuvant HIPEC, and HIPECT4 studied concurrent HIPEC and CRS. Although PROPHYLOCHIP and COLOPEC were negative trials, a great deal may be learned from their methodology, outcome measures, and patient selection criteria. HIPECT4 is the first RCT to show a clinical benefit of HIPEC in high-risk T4 colorectal cancer, demonstrating improved locoregional disease control with the addition of HIPEC to CRS with no increase in the rate of complications. This review critically examines the strengths and limitations of each major trial and discusses their potential impact on the practice of HIPEC. Several additional ongoing clinical trials also seek to investigate the role of HIPEC in preventing PM in advanced colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate interobserver agreement on the findings of baseline contrast-enhanced multidetector computed tomography (CE-MDCT) performed at the postoperative third month in patients who underwent surgery due to ductal adenocarcinoma of the pancreatic head and investigate the value of these findings in predicting locoregional recurrence. Material and methods: The baseline CE-MDCT images of 198 patients who underwent the Whipple procedure due to pancreatic head tumors were evaluated independently by three radiologists at the postoperative third month. The radiologists were asked to note suspicious findings in terms of locoregional recurrence, including postoperative fat stranding, the presence of perivascular contrast-enhanced solid tissue, short diameter of solid tissue if present, the shape of solid tissue (convex/concave), presence of peritoneal implants, diameter (mm) of pancreatic duct dilatation if present, the presence of lymph nodes larger than 5 mm, portal vein stenosis (≥50 and <50%), the presence of ascites, and the presence of distant metastases, as specified by the Society of Abdominal Radiology in October 2022. The agreement between the radiologists and the value of these parameters in predicting locoregional recurrence were investigated. Results: Among the CE-MDCT findings evaluated, the radiologists had a moderate-to-high level of agreement concerning the presence of perivascular contrast-enhanced solid tissue. However, there was a poor interobserver agreement on the shape of solid tissue. A very high level of agreement was found among the radiologists in the evaluation of pancreatic duct dilatation, peritoneal implants, ascites, and the presence of distant metastases. According to the univariate analysis, the rates of portal vein stenosis had a 1.419 -fold effect [odds ratio (OR)=1.419, [95% confidence interval (CI)= 0.548–3.679, p=0.041], lymph node presence had a 2.337 -fold effect [odds ratio (OR)=2.337, [95% confidence interval (CI)= 1.165–4.686, p=0.015], perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.241, [95% confidence interval (CI)= 1.072–4.684, p=0.005]. In the multivariate analysis, perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.519, [95% confidence interval (CI)= 1.132–5.605, p=0.024]. Conclusion: In the postoperative baseline CE-MDCT examination, the presence of solid tissue, lymph node presence, and portal vein stenosis in the surgical bed are among the findings that may indicate early locoregional recurrence in patients with pancreatic ductal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective: To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at 5 years. Background: Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At 3 years, LRF rate was comparable between TNT and chemoradiotherapy in the RAPIDO trial. Methods: A total of 920 patients were randomized between an experimental (EXP, short-course radiotherapy, chemotherapy, and surgery) and a standard-care group (STD, chemoradiotherapy, surgery, and optional postoperative chemotherapy). LRFs, including early LRF (no resection except for organ preservation/R2 resection) and locoregional recurrence (LRR) after an R0/R1 resection, were analyzed. Results: Totally, 460 EXP and 446 STD patients were eligible. At 5.6 years (median follow-up), LRF was detected in 54/460 (12%) and 36/446 (8%) patients in the EXP and STD groups, respectively (P=0.07), in which EXP patients were more often treated with 3-dimensional-conformed radiotherapy (P=0.029). In the EXP group, LRR was detected more often [44/431 (10%) vs. 26/428 (6%); P=0.027], with more often a breached mesorectum (9/44 (21%) vs. 1/26 (4); P=0.048). The EXP treatment, enlarged lateral lymph nodes, positive circumferential resection margin, tumor deposits, and node positivity at pathology were the significant predictors for developing LRR. Location of the LRRs was similar between groups. Overall survival after LRF was comparable [hazard ratio: 0.76 (95% CI, 0.46--1.26); P=0.29]. Conclusions: The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is a rare but aggressive biological subtype of breast cancer associated with higher locoregional and distant recurrence rates and lower overall survival despite advancements in diagnostic and treatment strategies. This review explores the evolving landscape of locoregional recurrence (LRR) in TNBC with improved surgical and radiation therapy delivery techniques including salvage breast conserving surgery (SBCS), re-irradiation, and thermo-radiation. We review current retrospective and prospective, albeit limited, clinical data highlighting the optimal management of locoregionally recurrent TNBC. We also discuss tumor genomic profiling and transcriptome analysis and review potential investigational directions. Significant progress has been made in the prevention of LRR but rates remain suboptimal, particularly in the TNBC population, and outcomes following LRR are poor. Further prospective studies are needed to identify the most effective and safest systemic therapy regimens and to whom it should be offered. There has been growing interest in the role of molecular markers, genomic signatures, and tumor microenvironment in predicting outcomes and guiding LRR treatment. Transcriptome analyses and biomarker-driven investigations are currently being studied and represent a promising era of development in the management of LRR. [ABSTRACT FROM AUTHOR]

Purpose. To compare the incidence of breast cancer (BC) relapse after subcutaneous mastectomy and Madden radical mastectomy.Patients and methods. The study included 102 patients diagnosed with BC with stages IIB – III, who underwent neoadjuvant drug therapy with a subsequent surgical stage of treatment on the basis of the Tver Regional Clinical Oncology Dispensary from 2017 to 2020. The main group included 50 patients who underwent subcutaneous mastectomy with simultaneous installation of an endoprosthesis: stage IIB – 31 (62 %) patients; stage III – 19 (38 %) patients. The comparison group included 52 patients who underwent surgical treatment in volume – radical mastectomy according to Madden (RME): Stage IIB – 34 (65.4 %) patients; stage III – 18 (34.6 %) patients. Depending on the subtype of the tumor, patients received neoadjuvant drug therapy.Results. During the three-year follow-up period, the progression of the disease after subcutaneous RME was detected in 7 (14 %) patients. Locoregional relapses accounted for 4 cases (8 %), progression to distant organs 3 cases (6 %). After the Madden RME, disease progression was detected in 6 (11.5 %) patients. Locoregional relapses accounted for 3 cases (5.7 %), progression to distant organs 3 cases (5.7 %). The detected foci did not always coincide with the primary subtype of the tumor: in 5 cases the subtype was different (38.5 %), in 8 cases it coincided (61.5 %).Conclusion. The frequency of development of locoregional and distant metastases did not statistically depend on the volume of surgical intervention (p > 0.05). It is reasonable to conduct a histological examination in case of progression to determine the tactics of treatment.

Abstract Background Recurrent/ metastatic squamous cell carcinoma of head and neck (R/M SCCNH) is still a difficult-to-treat disease with poor clinical outcomes and limited treatment choices. In view of locoregional recurrent versus distant metastatic SCCHN, the therapeutic efficacy of cetuximab-containing regimen and relevant prognostic factors for these two groups may be different. Thus, the aim of this study was to explore the treatment outcomes of cetuximab-containing regimen in locoregional recurrent and distant metastatic SCCHN groups, and to identify clinical factors correlated with better survival outcomes. Methods From 2016 to 2020, patients with R/M SCCHN who received cetuximab-containing regimen in our institute were enrolled in this study. Clinical outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were evaluated in both locoregional recurrence and distant metastasis groups. Exploratory analysis were conducted to investigate major clinical features associated with better outcomes. Results A total of 107 patients with locoregional recurrent SCCHN (N = 66) and distant metastatic SCCNH (N = 41) who received cetuximab-containing regimen were enrolled in this retrospective study. Patients with oral cavity cancer and patients with disease recurrence within 6 months after radiation therapy were significantly increased in locoregional recurrence group. The median OS (15.6 vs. 9.7 months, P = 0.004) and PFS (5.8 months vs. 4.2 months, P = 0.008) were longer in locoregional recurrence group than in distant metastasis group. In multivariate analysis of clinical features, locoregional recurrence was still an important risk factor associated with better OS (Hazzard ratio (HR) 0.64, p = 0.06) and PFS (HR 0.67, p = 0.075). In addition, a trend of favorable disease control rate (DCR; 62.5% vs. 45.0%, p = 0.056) was noted in locoregional recurrence group. In locoregional recurrence group, prior salvage surgery was associated with longer OS (HR = 0.24, P = 0.008) and PFS (HR = 0.30, P = 0.005). Conclusion SCCHN with locoregional recurrence is associated with better disease control and survival outcomes comparing to distant metastatic SCCHN when treated with cetuximab-containing regimen. Salvage surgery for locoregional recurrence may further improves clinical outcome.

Objective: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity. Methods: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo‐radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab. Results: Patients with HPV‐associated tumors and nonsmokers demonstrated improved overall and disease‐free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen. Conclusions: Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. Level of Evidence: 4. Both high dose and low dose cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People’s Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.3% and 28.1% (46% of which were mediastinal recurrences), respectively. We performed a meta-analysis of patients with pathologic (p) N0 to N2 disease to evaluate the risk factors for LR and to explore possible differences in recurrence risk between Asian population (AP) and non-Asian population (NAP). Methods: We identified all original studies of curative NSCLC surgical resection which reported risk of LR between January 1, 2000, and January 10, 2021, excluding studies with less than 10 LR, patients with metastatic disease, or any neoadjuvant therapy. A total of 87 studies were identified with pN0 to N2 disease; of these, 56 were of high quality (HQ) on the basis of the Newcastle-Ottawa Scale. For each risk factor, we derived pooled relative risk (RR) and 5-year rate estimates using random-effects models. Results: Overall, the three significant highest pooled RRs (95% confidence intervals) for LR were pN2 versus pN0 (3.01, 1.39–6.55), lymphovascular invasion (1.92, 1.58–2.33), and advanced pT3–4 stage versus pT1 (1.86, 1.53–2.25). For HQ studies, the highest RRs for LR were lymphovascular invasion (1.94, 1.57–2.40), sublobar versus lobar resection (1.86, 1.46–2.36), and pN1 versus pN0 (1.84, 1.37–2.47), but pN2 versus pN0 was no longer significant (3.0, 0.57–15.61), on the basis of only two eligible studies. The RRs for LR were consistent for most factors in AP and NAP, although the RR for male versus female sex was higher in AP (1.44, 1.21–1.72) than in NAP (1.09, 0.99–1.19). Where reported, the pooled rate of LR at 5 years was lower in AP (12.0%) than in NAP (22.7%), despite similar overall 5-year recurrence rates (both LR and distal) in both populations: 38.0% in AP and 37.3% in NAP. Nevertheless, a lower 5-year mortality rate was noted in AP (24.3%) than in NAP (45.9%). Conclusions: There is little high-quality evidence to support the hypothesis that pN2 disease is a risk factor for LR, but LR seems to be lower in Asians. Prospective evaluation of LR factors and rates may be necessary before further prospective evaluation of PORT, because it may not depend on nodal status alone. Recurrence rates may differ in Asians. The impact of mutational status and modern treatment including targeted therapies and immune checkpoint inhibitors is inadequately studied.

Purpose: This study aimed to examine the clinical characteristics and outcomes of patients with estrogen receptor-negative (ER−)/progesterone receptor-positive (PR+) early breast cancer. We also aimed to investigate the benefits of adjuvant endocrine therapy (ET) in this patient population. Methods: Patients with early breast cancer diagnosed at West China Hospital were divided into the ER−/PR+, ER+, and ER−/PR− groups. The chi-square test was used to analyze differences in clinical and pathological features among the groups. Multivariable Cox and Fine–Gray regression models were used to compare mortality and locoregional recurrence (LRR)/distant recurrence (DR), respectively. We performed a subgroup analysis to determine which ER−/PR+ patients can benefit more from ET. Results: From 2008 to 2020, we enrolled 443, 7104, and 2892 patients into the ER−/PR+, ER+, and ER−/PR− groups, respectively. The ER−/PR+ group showed more unfavorable clinical features and aggressive pathological characteristics than the ER+ group. The mortality, LRR, and DR rates were higher in the ER−/PR+ than in the ER+ group. Most clinical features and pathological characteristics were similar between the ER−/PR+ and ER−/PR− group and their outcomes were comparable. In the ER−/PR+ group, patients who received ET showed significantly lower LRR and mortality rates than those who did not; however, no difference was observed in DR. Subgroup analysis suggested that ER−/PR+ patients age ≥ 55 years, and postmenopausal status can benefit from ET. Conclusion: ER−/PR+ tumors have more aggressive pathological characteristics and more unfavorable clinical features than ER+ tumors. ET can reduce the LRR and mortality rates in ER−/PR+ patients. Postmenopausal and age ≥ 55 years ER−/PR+ patients can benefit from ET. [ABSTRACT FROM AUTHOR]

Background: Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non‐small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. Methods: A total of 118 patients who underwent tumor resection with mutation‐detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Results: Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3‐year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR‐free survival as compared to patients with wild‐type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Conclusions: Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis. [ABSTRACT FROM AUTHOR]