Supraclavicular Node Metastasis Research Articles

Supraclavicular lymph node metastasis should not be defined as regional lymph node metastasis in cervical and upper thoracic esophageal squamous cell carcinoma.

The importance of supraclavicular lymph node (SCLN) metastasis in cervical and upper thoracic esophageal squamous cell carcinoma (ESCC) has not been determined. The aim of the present study was to provide a detailed definition of the range of SCLN regions and to explore whether SCLNs should be considered as a regional lymph nodes for patients with cervical and upper thoracic ESCC. A retrospective analysis was performed on 230 patients with locally advanced cervical or upper thoracic ESCC who underwent radical radiotherapy and chemotherapy. The range of SCLN regions was defined in detail on contrast enhanced computed tomography images of the neck. According to whether the patient had lymph node metastasis in the supraclavicular region, the included patients were divided into two groups, and the survival differences and reasons for treatment failure between the two groups were analyzed. Of the 230 patients with ESCC, 71 (30.87%) exhibited lymph node metastases in the supraclavicular region. The median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 30 months, respectively (P<0.001). After propensity score matching (PSM), the median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 28 months, respectively (P<0.001). During the follow-up period, there were a total of 101 cases of failure of treatment in the irradiation field, 6 cases had esophageal metastasis in the non-irradiated field and 27 cases had regional lymph node metastasis in the non-irradiated field. In addition, there were 33 cases of metastasis to the distant lymph nodes or organs. There was no significant difference in the local treatment failure rate between the groups with or without SCLN metastasis in both the irradiation field and the non-irradiation field, but the probability of distant metastasis in the SCLN metastasis group was significantly higher than that in the group without SCLN metastasis (P=0.025). In conclusion, patients with cervical and upper thoracic ESCC with SCLN metastasis have a poor prognosis and the median overall survival time is closer to that of metastatic ESCC than ESCC with regional lymph node metastasis; therefore, SCLNs should not be defined as regional lymph nodes in patients with cervical and upper thoracic ESCC.

Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer

Introduction Ado-trastuzumab emtansine (T-DM1) is employed in the treatment of patients with HER2-positive breast cancer. The most common side effects are fatigue, diarrhoea, anaemia, transaminase elevation and drug-induced thrombocytopenia. This report describes a patient with metastatic breast cancer who developed drug-induced lupus due to T-DM1. Case Report A 54-year-old woman was diagnosed with breast cancer in March 2018. She underwent modified radical mastectomy and axillary lymph node dissection (pT2N1aM0). Following supraclavicular lymph node metastasis in May 2018, she received 8 cycles of docetaxel, trastuzumab, and pertuzumab. In December 2020, the patient presented with axillary and intra-abdominal lymph node metastases, along with bone metastases observed on PET/CT scan. Treatment with T-DM1 and zoledronic acid was initiated. After 18 months on T-DM1, she developed drug-induced lupus. Her symptoms resolved with hydroxychloroquine treatment and discontinuation of T-DM1. Discussion Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.

555. SUPRACLAVICULAR NODE INVOLVEMENT, A NODAL OR METASTATIC DISEASE? - A 10-YEAR EXPERIENCE IN ESOPHAGEAL CARCINOMA AT A TERTIARY REFERRAL CENTRE

Abstract Background Despite the advance in neoadjuvant chemothepray/chemoradiotherapy and favourable outcomes of surgical management in supraclavicular lymph node (SCLN) involvement reported in recent studies, the latest AJCC/UICC TMN classification still regards SCLN metastasis as extra-regional i.e Stage IVB (M1) disease. The role of SCLN dissection and surgical management remain controversial. At National University Hospital of the present study, bilateral supraclavicular lymphadenectomy is routinely performed for resectable thoracic ESCC. The aim of this retrospective cohort study is to investigate the long-term outcome of surgical management in pathological SCLN metastasis and its survival benefit comparing to Stage IIB-IVA diseases. Methods Patients with ESCC who underwent esophagectomy and 3-field lymphadenectomy with curative intent between January 2013 and January 2023 at the single centre were included; cases of salvage esophagectomy post-definitive concurrent chemoradiotherapy, palliative resections, and concurrent head and neck cancers were excluded. Neoadjuvant treatments were considered in cases staged clinically as T2 and/or N1 or greater. Pathological status of lymph nodes was recorded according to JES classification. Demographics and prognostic factors were examined using univariant analysis of overall survival (OS). Patients with SCLN metastases and other LN involvements were compared and OS were analysed using Kaplan-Meier method. Results 544 patients were included. 183 had one or more pathological LN metastasis (pN1:126, pN2 46, and PN3: 11) in which 55 patients had SCLN metastasis. Patients with LN metastasis had poorer prognosis than those without (pN0) with a Hazard Ratio (HR) of 2.68 (95% CI, 1.12-3.40, p&amp;lt;0.01); similar pattern was seen in patients with SCLN metastasis (HR 2.28, p&amp;lt;0.01). The 3-year and 5-year OS of patients with SCLN metastasis was 18.5% and 11.6% respectively whereas those of other LN metastasis was 21.4% and 15.8%; the difference between the groups was not statistically significant (p=0.525) (graph 1). Conclusion Lymph node status (pN) is a well-recognised prognostic factor as reaffirmed, however, within the pN positive cohort, long-term survival of patients with SCLN metastasis, considered as stage IVB (M1), was comparable (p&amp;lt;0.05) to those with other LN metastases. This supports the survival benefit of surgical resection with neoadjuvant therapy in SCLN metastases as following nodal disease treatment algorithm; further evaluation including systemic therapy and lymph node sub-group analysis is being conducted. Whilst randomised controlled trials such as Japanese JCOG2013 provides level I evidence, the present study provides complementary real-world experience for SCLN dissection.

256. PROGNOSIS AND RISK FACTORS FOR SUPRACLAVICULAR LYMPH NODE METASTASIS IN PATIENTS WITH MIDDLE AND LOWER THORACIC ESOPHAGEAL CANCER

Abstract Background Whether supraclavicular lymph node metastases (#104 LNM) in patients with thoracic esophageal cancer are classified as distant or regional metastases differs between Western countries and East Asia. Therefore, in Japan, 3FL is a standard procedure, but in Western countries, 3FL may be rarely practiced. We aimed to determine the frequency and prognosis of #104 LNM compared with other regional LN stations and to identify risk factors for #104 LNM in patients with advanced thoracic esophageal cancer to investigate value of treatment of #104 LNM. Methods The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy radically from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography positive LNs. The effectiveness of LN dissection was assessed using an efficacy index (EI) that we calculated by multiplying the rate of metastasis (%) to each LN station by the 5-year overall survival (OS) rate of each patient and then dividing by 100. In order to clarify the indication for 3FL, risk factors for #104 LNM were determined by multivariable logistic regression. Results Among of 567 patients, 66 (11.6%) had #104 LNM. #104 LNM occurred in 31.7%, 10.7%, and 5.6% of patients with upper, middle, and lower thoracic lesions respectively. All patients had squamous cell carcinoma. Neoadjuvant chemotherapy was administered to 71% of patients, and chemo-radiation to 11%. The 5-year OS was 45.8%. The EI for #104 LNs (5.3) was like that for #101 LNs. Risk factors were age &amp;lt;65 years, upper lesion, clinical stage N2–3, and #101/106rec LNM. When assessing only middle and lower lesions, the 5-year OS of patients was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs, with similar risk factors to overall population. Conclusions The EI of patients with #104 LNM was similar to that of patients with other regional LNM such as #101 and #8/9/11 LNs, Therefore, patients with #104LNM were worth treated LN dissection. However, we recommend 3FL exclusively for patients with #104 LNM or those at high risk of metastasis due to the overall metastatic rate not being high.

The therapeutic value of ipsilateral supraclavicular lymphadenectomy in locally advanced breast cancer: A review.

The treatment of isolated ipsilateral supraclavicular lymph node metastasis for locally advanced breast cancer has always been a controversial issue for breast surgeons. However, with the further understanding of the metastasis and treatment of breast cancer, it is now considered to be a locally advanced disease, and there is a new debate on the treatment of isolated ipsilateral supraclavicular lymph node metastasis. The author reviewed the relevant literature and briefly discussed the clinical significance of supraclavicular lymph node resection in patients with locally advanced breast cancer presenting with isolated ipsilateral supraclavicular lymph node metastasis.

Long-term survival analysis of robotic esophagectomy for esophageal cancer.

Robotic esophagectomy has improved early outcomes and enhanced the quality of lymphadenectomy for esophageal cancer surgery. This study aimed to determine risk factors for long-term survival following robotic esophagectomy and the causes of long-term mortality. We included patients who underwent robotic esophagectomy at our institute between 2010 and 2022. Robotic esophagectomy was defined as a surgical procedure performed robotically in both the abdomen and thorax. Robotic esophagectomy was performed in patients at all stages, including advanced stages, even in patients with stage IV and supraclavicular lymph node metastasis. A total of 340 patients underwent robotic esophagectomy during the study period. Ivor-Lewis operation and McKeown operation were performed on 153 (45.0%) and 187 (55.0%) patients, respectively. The five-year survival rates based on clinical stages were as follows: 85.2% in stage I, 62.0% in stage II, 54.5% in stage III, and 40.3% in stage IV. Risk factors for long-term survival included body mass index, Charlson comorbidity index, clinical stages, and postoperative complications of grade 4 or higher. Among the cases of long-term mortality, recurrence accounted for 42 patients (61.7%), while non-cancer-related death occurred in 26 patients (38.2%). The most common cause of non-cancer-related death was malnutrition and poor general condition, observed in 11 patients (16.2%). Robotic esophagectomy has demonstrated the ability to achieve acceptable long-term survival rates, even in patients with cervical lymph node metastasis. However, addressing high-grade postoperative complications and long-term malnutrition remains crucial for further improving the long-term survival outcomes of patients with esophageal cancer.

Clinical significance of supraclavicular lymph node (SCLN) dissection for patients with breast cancer with ipsilateral SCLN metastasis.

e13110 Background: Breast cancer with ipsilateral supraclavicular lymph node (SCLN) metastasis is defined as Ⅲc stage according to the 8th AJCC system. It is still pending whether to exert SCLN dissection except for regional radiotherapy to such patients. Methods: Breast cancer patients with ipsilateral SCLN metastasis from 2019.02 to 2024.01 in multiple centers in Hubei China, were enrolled. Patients received either SCLN radiotherapy alone or combined with SCLN dissection. All patients received standard therapy recommended by the NCCN guidelines. The primary endpoint was 5-year disease free survival (DFS), and secondary endpoints were complication rates, overall survival (OS), and quality of life scores. Results: As of 2024.01, a total of 181 patients with a median age of 51 years (28-78 years) were enrolled. 177 patients received neoadjuvant therapy and 4 patients underwent surgery followed by adjuvant therapy. The molecular subtyping composition was Luminal (HR+, HER2-, 38%), TNBC (triple negative breast cancer, HR-, HER2-, 23%), HER2+ (HR-, HER2+, 20%) and TPBC (triple positive breast cancer, HR+, HER2+, 19%). Of the 177 neoadjuvant treated-patients, 71.2% did not achieve pathological complete response (pCR). The percentage of molecular subtyping in non-pCR neoadjuvant patients was Luminal 45%, TNBC 26%, HER2+ 15%, and TPBC 14%, while those who got pCR were HER2+ 35%, TPBC 31%, Luminal 18%, and TNBC 16%. A total of 27 recurrent and/or metastatic events occurred, with 14.5% (8/55) in the experimental group (with SCLN dissection) and 15.1% (19/126) in the control group; while Luminal accounted for 13.4% (9/67), TPBC 13.9% (5/36), HER2+ 16.2% (6/37) and TNBC 17.1% (7/41). Using questionnaires, we found that both groups resulted in comparable complication rates, and quality of life scores were better in the group that did not undergo SCLN dissection. Conclusions: According to the preliminary results, we found several interesting phenomena. First, patients with SCLN metastasis had a higher percentage of HER2 overexpression, including HER2+ and TPBC, up to 39%. Second, receiving neoadjuvant therapy, TPBC and HER2+ subtypes were more likely to achieve pCR, possibly due to the use of dual-targeted agents. Third, even the median follow-up time has not yet been reached, preliminary data suggested that the recurrent and metastatic rates were comparable in both groups and four subtypes. These data seem to suggest that in patients with ipsilateral SCLN metastasis, SCLN dissection is not mandatory with effective systematic therapy and radiotherapy. In addition, for Luminal subtype, adjuvant therapy should not be taken lightly, while for HER2 overexpressing and TNBC subtypes, the necessity of intensive therapy is no longer purposely highlighted. Of course, we also look forward to the final statistical analysis of the differences in the primary endpoints to bring us a better answer. Clinical trial information: NCT03716245 .

High versus standard radiation dose of definitive chemoradiotherapy combined with immunotherapy for inoperable esophageal squamous cell carcinoma: A multicenter propensity score matching analysis.

e16118 Background: There is no consensus of the radiation dose for esophageal squamous cell carcinoma (ESCC) in the setting of definitive chemoradiotherapy (dCRT) combined with immunotherapy. This study aimed to compare the efficacy and safety of high-dose (HD) versus standard-dose radiotherapy (SD) for locally inoperable ESCC. Methods: Patients with locally advanced unresectable ESCC or advanced ESCC with supraclavicular lymph node metastases only who received high-dose (≥ 60Gy) or standard-dose (50-50.4Gy) radiation in dCRT combined with anti-PD-1 antibody as the first-line treatment from four academic cancer centers were enrolled. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. Results: Between March 2019 and July 2022, 328 patients were enrolled from four cancer centers in China, with 163 patients in the HD and 165 patients in the SD groups, respectively. The median follow-up time in the HD and SD groups were 28.9 and 25.9 months, respectively. There was no significant difference in overall survival (OS) (median OS: not reached in both, P = 0.080), progression-free survival (PFS) (median PFS: not reached vs. 30.3 months, P = 0.073), locoregional progression-free survival (LRPFS) and distant metastasis survival (DM) between the HD and SD groups. After 1:2 PSM, 156 patients in the HD and 78 patients in the SD groups were selected for further analyses. The results remained consistent and showed that the HD group had no significant benefits in OS (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.50-1.51, P = 0.624), PFS (HR = 0.79, 95%CI = 0.51-1.23, P = 0.300), LRPFS (HR = 0.75, 95%CI = 0.47-1.19, P = 0.228) and DM (HR = 1.05, 95%CI = 0.64-1.73, P = 0.849), compared with the SD group. In terms of failure patterns, the incidences of locoregional failure only (13.5% vs. 16.7%, P = 0.512), distant failure only (10.9% vs. 9.0%, P = 0.648) and synchronous locoregional and distant failure (2.6% vs. 6.4%, P = 0.164) were similar between two groups. No significant difference was found in the incidences of hematological toxicities, esophagitis, pneumonia (12.2% vs. 10.3%, P = 0.664) and fistula (7.1% vs 9.0%, P = 0.603) between the HD and SD groups. Conclusions: Compared with a radiation dose of 50-50.4Gy, the increase in radiation dose (≥60Gy) did not result in survival benefits for inoperable ESCC patients receiving dCRT combined with immunotherapy. Furthermore, similar failure patterns and toxicities were observed between the two treatment groups.

Risk factors and prognosis for supraclavicular lymph node metastasis in patients with thoracic esophageal cancer. Distant or regional metastasis?

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high.

Prognostic factors and the role of primary debulking in operable stage IVB ovarian cancer with supraclavicular lymph node metastasis: a retrospective study in Chinese patients

BackgroundRecent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis.MethodsWe retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT).ResultsIn 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as “continuous-metastasis type”, while the other 7 (13.7%) defined as “skip-metastasis type”. Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3–63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that “continuous-metastasis type” had longer OS and PFS than “skip-metastasis type” (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among “continuous-metastasis type” patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors.ConclusionsIn stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as “continuous-metastasis type” with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.

Risk of thoracic soft tissue sarcoma after breast cancer radiotherapy: a population-based cohort study in Osaka, Japan.

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7years (interquartile range, 4.0-8.6years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population.

Effect of cervical paraesophageal lymph node metastasis versus supraclavicular lymph node metastasis on the overall survival of patients with thoracic esophageal squamous cell carcinoma: an observational study.

Esophageal cancer (EC) is a major global health burden, with a particularly high incidence in East Asia. The authors aimed to investigate the effect of metastasis in cervical paraesophageal lymph nodes (station 101) and supraclavicular lymph nodes (station 104) on the survival of patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC). Data were obtained from the database of the authors' hospital. The authors retrospectively analyzed the patients with EC who underwent esophagectomy from January 2010 to December 2017. These patients were allocated into two groups based on the presence of lymph node metastasis (LNM) in the cervical paraesophageal or supraclavicular regions. Clinical outcomes and survival data were compared using the TNM staging system of the 8th edition of the American Joint Committee on Cancer (AJCC). After a median follow-up of 62.1 months, 122 patients with LNM in the supraclavicular region were included in the study. Among these patients, 53 showed cervical paraesophageal LNM and an overall survival (OS) of 19.9 months [95% confidence interval (CI): 16.3-23.5]. In contrast, 69 patients showed supraclavicular LNM with an OS of 34.9 months (95% CI 25.7-44.1). The OS rates at 1, 3, and 5 years were 77%, 29%, and 21%, respectively, for patients with cervical paraesophageal LNM. Moreover, patients with supraclavicular LNM demonstrated OS rates of 88%, 48%, and 34%, respectively [Hazard ratio (HR): 0.634, 95% CI: 0.402-1.000, P=0.042]. Patients with ESCC with cervical paraesophageal LNM had significantly worse OS than those with supraclavicular LNM. This study underscores the importance of accurately identifying and managing ESCC with cervical paraesophageal LNM, as it may require more tailored and aggressive treatment strategies to prolong patient survival.

Identification of ipsilateral supraclavicular lymph node metastasis in breast cancer based on LASSO regression with a high penalty factor.

Aiming at the problems of small sample size and large feature dimension in the identification of ipsilateral supraclavicular lymph node metastasis status in breast cancer using ultrasound radiomics, an optimized feature combination search algorithm is proposed to construct linear classification models with high interpretability. The genetic algorithm (GA) is used to search for feature combinations within the feature subspace using least absolute shrinkage and selection operator (LASSO) regression. The search is optimized by applying a high penalty to the L1 norm of LASSO to retain excellent features in the crossover operation of the GA. The experimental results show that the linear model constructed using this method outperforms those using the conventional LASSO regression and standard GA. Therefore, this method can be used to build linear models with higher classification performance and more robustness.

Recurrence-free survival as a surrogate for overall survival in esophageal squamous cell carcinoma: Nationwide real-world data from Japan.

269 Background: One of the limitations of the established gold standard, overall survival (OS), is that it requires an extended follow-up period. Addressing this challenge involves investigating appropriate statistically and clinically relevant surrogate endpoints. However, there is a paucity of studies using real-world data (RWD) to explore surrogacy in patients with esophageal squamous cell carcinoma (ESCC). Our study aims to investigate whether recurrence-free survival (RFS) is a valid surrogate endpoint for OS in surgically resectable advanced ESCC patients, utilizing a comprehensive nationwide database in Japan. Methods: The ESCC patients who received neoadjuvant CF (cisplatin and 5-fluorouracil) or DCF (docetaxel, cisplatin and 5-fluorouracil) at 58 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. Kendall's tau between RFS and OS was used at the individual level, and the coefficient of determination was used at the institutional level to assess surrogacy. Additionally, surrogacy between each short-term postoperative endpoint (pathological complete response [pCR] or pathological grade) and OS was investigated using novel statistical methods. Results: Our study encompassed 3154 ESCC patients who underwent subtotal esophagectomy from 2010 to 2015. The cStage I/II/III/IVA/IVB (due to supraclavicular lymph node metastasis) was 224 (7.1%), 1008 (32.0%), 1664 (52.8%), 117 (3.7%), and 140 (4.4%), respectively. The 5-year OS and RFS rate for the entire cohort was 56.6% and 47.7%, respectively. In the primary analysis, a strong correlation between RFS and OS was found (Kendall's tau = 0.797, 95% confidence interval [CI]: 0.782 to 0.812) at the individual level. Subgroup analysis revealed that the better the pathological response, the higher the tau value. An adjusted R2 of 100.0% (95% CI: 40.2 to 100.0) was obtained with the meta-regression model at the institutional level. The surrogate threshold effect was 0.703. Tau between pCR or pathological grade and OS were -0.025 (95% CI: -0.335 to 0.285) and 0.062 (95% CI: -0.086 to 0.209), respectively. Conclusions: The present study was the first nationwide RWD investigation to demonstrate a strong correlation between RFS and OS in surgically resectable ESCC patients who underwent neoadjuvant chemotherapy (NAC). Notably, this correlation was more pronounced in patients who had a more effective response to NAC. These findings hold promise for expediting the development of novel neoadjuvant treatment by shortening the duration of clinical trials.

Current status and prospects of diagnosis and treatment for esophageal cancer with supraclavicular lymph node metastasis.

Patients with supraclavicular lymph node (SLN) metastasis from esophageal cancer encounter significant variations in treatment approaches due to differences in pathological subtypes and the lack of a unified regional staging system between East Asian and Western countries. The Tiger study aims to develop an internationally recognized staging system and to delineate the extent of regional lymph node dissection. In the context of esophageal squamous cell carcinoma (SCC) with SLN metastasis, the treatment paradigms from East Asia offer valuable insights. The Japan Esophageal Society (JES) 12th edition staging system guides a tailored comprehensive treatment strategy, emphasizing either radiotherapy and chemotherapy or surgical intervention. In contrast, esophageal adenocarcinoma (AC) predominates in Western countries, where the 8th edition of the American Joint Committee on Cancer (AJCC) staging system classifies SLN metastasis as a distant metastasis, advocating for systemic therapy as the primary treatment modality. Nonetheless, compelling evidence suggests that a multidisciplinary treatment approach, incorporating either radiotherapy and chemotherapy or surgery as the initial treatment, can yield superior outcomes for these patients compared to chemotherapy alone.

Local imaging to interpret tumor size in F18 fluorodeoxyglucose positron emission tomography/CT in lung cancers.

This study aimed to determine the thoracic and extra-thoracic extension of the disease in patients diagnosed with lung cancer and who had whole-body F18-fluorodeoxyglucose positron emission tomography/CT imaging and to investigate whether there is a relationship between tumor size and extrathoracic spread. A total of 308 patients diagnosed with lung cancer were included in this study. These 308 patients were first classified as group 1 (SPN 30 mm>longest lesion diameter ≥10 mm) and group 2 (lung mass (longest lesion diameter ≥30 mm), and then the same patients were classified as group 3 (nodular diameter of ≤20 mm) and group 4 (nodular size of >20 mm). Group 1 was compared with group 2 in terms of extrathoracic metastases. Similarly, group 3 was compared with group 4 in terms of frequency of extrathoracic metastases. F18 fluorodeoxyglucose positron emission tomography/CT examination was used to detect liver, adrenal, bone, and supraclavicular lymph node metastasis, besides extrathoracic metastasis. Liver, bone, and extrathoracic metastasis in group 1 was statistically lower than in group 2 (p<0.001, p<0.01, and p=0.03, respectively). Liver, extrathoracic, adrenal, and bone metastasis in group 3 was statistically lower than that in group 4 (p<0.001, p=0.01, and p=0.04, p<0.01, respectively). The extrathoracic extension was observed in only one patient in group 3. In addition, liver, adrenal, and bone metastases were not observed in group 3 patients. Positron emission tomography/CT may be more appropriate for cases with a nodule diameter of ≤20 mm. Performing local imaging in patients with a nodule diameter of ≤20 mm could reduce radiation exposure and save radiopharmaceuticals used in positron emission tomography/CT imaging.

Prognosis of patients with residual pathological disease after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy and surgery for esophageal squamous cell carcinoma: a retrospective cohort study.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy has been established as one of the standard neoadjuvant therapies for locally advanced esophageal squamous cell carcinoma (ESCC). However, little is known about prognostic factors in patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC who are candidates for adjuvant nivolumab. This study aimed to investigate prognostic factors in patients with residual pathological disease after neoadjuvant DCF chemotherapy followed by surgery for locally advanced ESCC. This was a retrospective cohort study. This retrospective cohort study included patients who received neoadjuvant DCF followed by surgery for locally advanced ESCC between June 2014 and January 2020 at the National Cancer Center Hospital East. Among a total of 210 patients, 45 patients (21.4%) achieved a pathological complete response. The 3-year disease-free survival (DFS) rate was significantly lower in patients with residual pathological disease than in those with a pathological complete response [53.5% versus 74.5%; hazard ratio (HR): 2.09, 95% confidence interval (CI): 1.16-3.77, p = 0.01]. In patients with residual pathological disease (n = 165), multivariate analysis revealed that pathological node positivity (HR: 3.59, 95% CI: 1.92-6.71, p < 0.01), supraclavicular lymph node metastasis (HR: 2.15, 95% CI: 1.19-3.90, p = 0.01), and lymphovascular invasion (HR: 1.90, 95% CI: 1.14-3.17, p = 0.02) were significantly associated with poor DFS. In this largest-to-date cohort study, patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC had a poor prognosis. In these patients, pathological node positivity, including supraclavicular lymph node metastasis, and lymphovascular invasion were considered significant prognostic factors.

Clinical and Pathologic Supraclavicular Lymph Node Metastases in Esophageal Squamous Cell Carcinoma Treated by Esophagectomy with Three-Field Lymph Node Dissection.

This study investigated the survival outcomes for surgically treated esophageal squamous cell carcinoma (ESCC) patients based on clinically suspicious supraclavicular lymph node (SCN) metastasis (cSCN+) and pathologically confirmed SCN metastasis (pSCN+). Using an institutional registry between 1994 and 2018, this study retrospectively analyzed 611 patients who received curative-intent esophagectomy with 3-field lymph node dissection for ESCC. The study used computed tomography and positron emission tomography to define cSCN+. Among 611 patients, 24.4% had cSCN+ and 12.2% had pSCN+. The 5-year overall survival (OS) rates were 68.2% for cN0, 43.5% for cN+ without cSCN+, and 30.3% for cN+ with cSCN+ (p = 0.018). Although the univariable analysis showed that cSCN+ was associated with poorer survival than cN0 or cN+ with cSCN- (hazard ratio [HR], 1.818; p < 0.001), the multivariable analysis did not support this finding (HR, 1.281; p = 0.681). The 5-year OS rates were 64.2% for pN0, 41.5% for pN+ without pSCN+, and 25.6% for pN+ with pSCN+ (p = 0.054). Univariable analysis showed an association of pSCN+ with poor OS (HR, 1.830; p < 0.001), but the difference in the multivariable analysis was not significant (HR, 0.912; p = 0.587). The presence of SCN metastasis did not have a significant impact on the OS of ESCC patients with 3-field lymph node dissectionregardless of clinical suspicion or pathologic confirmation.

Optimization of supraclavicular lymph node clinical target volume delineation in high-risk breast cancer: a single center experience and recommendation

BackgroundProphylactic irradiation of supraclavicular lymph node drainage areas can improve the regional control rate of lymph node-positive or lymph node-negative disease but a locally-advanced stage breast cancer, and it can reduce breast cancer-related mortality. However, many controversies exist in the clinical target volume delineation of supraclavicular lymph node drainage in patients with breast cancer.MethodsWe retrospectively analyzed 42 patients with breast cancer and supraclavicular lymph node metastasis at our hospital between January 2017 and December 2021. Among these cases, 32 were locally advanced and 10 were stage IV at initial treatment. A patient with breast cancer who did not undergo dissection of the supraclavicular and infraclavicular lymph nodes at our hospital was selected as a standard patient. A contrast-enhanced computed tomography (CT) scan for positioning was used as a template image, and blood vessels, muscles, and bony landmarks were used as references for positioning. The metastatic supraclavicular lymph nodes were identified in all enrolled patients and projected into the template CT images.ResultsThe metastastic pattern of supraclavicular lymph node in breast cancer was proposed: distribution along the posterolateral border of the internal jugular vein (medial supraclavicular group) and along the transverse jugular vein (lateral supraclavicular group). We theorized that the lateral and posterior borders of the clinical target volume in the supraclavicular region should include the lymph nodes in the posterior triangle of the neck (level V) in high-risk individuals. If the metastatic axillary lymph node is extensive, then the superior border of the supraclavicular region should be moved upward appropriately.ConclusionsThis study analyzed patients with breast cancer and supraclavicular lymph node metastasis at initial treatment, explored the metastastic pattern of supraclavicular lymph node, and applied anatomical knowledge to further optimize the target volume delineation of supraclavicular lymph node drainage area in high-risk breast cancer.

Role of aggressive locoregional surgery in treatment strategies for ipsilateral supraclavicular lymph node metastasis of breast cancer: a real-world cohort study.

Background: Breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastases (ISLNM) have unfavorable prognoses. The role of supraclavicular lymph node dissection (SLND) as a surgical intervention in the treatment of this condition remains controversial. In this study, we aimed to evaluate the prognostic factors associated with breast cancer with ISLNM and to assess the potential impact of aggressive locoregional surgical management on patient outcomes. Methods: We conducted a retrospective analysis of 250 breast cancer patients with ISLNM who were treated with curative intent at our institution between 2000 and 2020. The cohort was stratified into groups based on the extent of axillary surgery. The first group, comprising 185 patients, underwent level I/II axillary dissection. The second group, consisting of 65 patients, underwent aggressive locoregional surgery, including levels I/II/III (infraclavicular) dissection in 37 patients and levels I/II/III + SLND in 28 patients. Our study evaluated overall survival (OS) and disease-free survival (DFS) as primary endpoints, and locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) as secondary endpoints. Results: The median follow-up time among all patients was 5.92years (1.05-15.36years). The 5-year OS rate was 71.89%, while the DFS rate, LRRFS rate, and DMFS rates were 59.25%, 66.38%, and 64.98%, respectively. A significant difference in OS, DFS, LRRFS, and DMFS was observed between the second group and the first group (p < 0.01). No beneficial impact on recurrence, metastasis, or survival outcomes was observed in the levels I/II/III + SLND group compared to the levels I/II/III dissection group. Multivariate logistic regression analysis revealed that levels I/II/III ± SLND surgery and T stage were associated with OS (p = 0.006 and p = 0.026), while levels I/II/III ± SLND surgery, ER+/HER2-, and histologic grade were associated with DFS (p = 0.032, p = 0.001, p = 0.032). Conclusion: Breast cancer with ISLNM may be considered a locoregional disease, requiring a combination of systemic and local therapies. Aggressive locoregional surgery has been shown to positively impact recurrence, metastasis, and survival outcomes. This approach may provide improved management of the ISLNM for breast cancer patients.