Locoregional Lymph Node Recurrence Research Articles

Safety and Efficacy of Computed Tomography–Guided Iodine-125 Brachytherapy as a Salvage Treatment for Locoregional Lymph Node Recurrence of Esophageal Cancer

PurposeTo investigate the clinical safety and efficacy of computed tomography (CT)–guided iodine-125 (125I) brachytherapy as a salvage treatment for esophageal cancer with locoregional lymph node recurrence (LNR). Materials and MethodsThis retrospective study included patients with esophageal cancer who developed locoregional LNR after initial curative resection followed by CT-guided 125I brachytherapy as a salvage treatment (January 2014 to January 2020). Local tumor progression–free survival (LTPFS) was assessed using Response Evaluation Criteria in Solid Tumors, v1.1. Clinical response was evaluated with the Numerical Rating Scale pain score, and adverse events were evaluated with the Common Terminology Criteria for Adverse Events (v5.0). A layered Cox proportional hazards model was used to determine independent factors affecting LTPFS. ResultsA total of 52 patients (mean age, 60 years) were included in this study. The median follow-up was 9.3 months (range, 4.3–12 months). The median LTPFS was 7.0 months (interquartile range, 5.0–9.5 months). The local control rates were 100%, 94.2%, 59.6%, and 13.4% at 1, 3, 6, and 12 months, respectively. The overall survival rates were 100%, 100%, 82.6%, and 36.5% at 1, 3, 6, and 12 months, respectively. The number of locoregional LNRs (hazard ratio [HR], 2.38 [95% confidence interval {CI}, 1.11–5.10]; P = .026), clinical stage at diagnosis (HR, 8.12 [95% CI, 3.19–20.66]; P < .001), and pathologic stage (HR, 5.74 [95% CI, 2.14–15.39]; P = .001) were independent factors for LTPFS. The rate of pain relief was 96.4% (27 of 28). Treatment-related death was not observed. ConclusionsCT-guided 125I radioactive seed implantation resulted in pain relief and short to midterm local control.

Computed tomography-based radiomic analysis for prediction of treatment response to salvage chemoradiotherapy for locoregional lymph node recurrence after curative esophagectomy.

ObjectiveTo investigate the capability of computed tomography (CT) radiomic features to predict the therapeutic response and local control of the locoregional recurrence lymph node (LN) after curative esophagectomy by chemoradiotherapy.MethodsThis retrospective study included 129 LN from 77 patients (training cohort: 102 LN from 59 patients; validation cohort: 27 LN from 18 patients) with postoperative esophageal squamous cell carcinoma (ESCC). The region of the tumor was contoured in pretreatment contrast‐enhanced CT images. The least absolute shrinkage and selection operator with logistic regression was used to identify radiomic predictors in the training cohort. Model performance was evaluated using the area under the receiver operating characteristic curves (AUC). The Kaplan–Meier method was used to determine the local recurrence time of cancer.ResultsThe radiomic model suggested seven features that could be used to predict treatment response. The AUCs in training and validated cohorts were 0.777 (95% CI: 0.667–0.878) and 0.765 (95% CI: 0.556–0.975), respectively. A significant difference in the radiomic scores (Rad‐scores) between response and nonresponse was observed in the two cohorts (p < 0.001, 0.034, respectively). Two features were identified for classifying whether there will be relapse in 2 years. AUC was 0.857 (95% CI: 0.780–0.935) in the training cohort. The local control time of the high Rad‐score group was higher than the low group in both cohorts (p < 0.001 and 0.025, respectively). As inferred from the Cox regression analysis, the low Rad‐score was a high‐risk factor for local recurrence within 2 years.ConclusionsThe radiomic approach can be used as a potential imaging biomarker to predict treatment response and local control of recurrence LN in ESCC patients.

Loco-regional therapy for isolated locoregional lymph node recurrence of breast cancer: focusing on surgical treatment with combined therapy

Advances have been made in systemic as well as locoregional treatment of primary breast cancer. Evidence, based established therapeutic strategies, for isolated locoregional lymph node recurrence is not yet sufficient. In this series, we focused especially on isolated axillary lymph node recurrence (AR) and supraclavicular lymph node recurrence (SR) in patients receiving systemic and/or radiation therapy combined with surgery. Disease free survival (DFS) in patients with AR ranged from 20 to 36 months. From 69% to 77% of all patients underwent surgical excision. The 5-year overall survival (OS) ranged from 39% to 46%. Positive lymph node metastases of primary cancer, size of the primary tumor, and R0 resection were associated with good outcomes. Longer DFS is associated with good outcomes. Limited SR data showed DFS to range from 25–27%. Median progression free survival (PFS) was 18 months, 5-year OS rates were 24–42%, and 5-year OS were 29–34 months. Combination therapy was an independent factor associated with better PFS as compared to local therapy only. Salvage treatment and grade of the primary tumor significantly were associated with OS on multivariate analysis. Available data, retrospective and not randomized, showed therapy combining systemic treatments and/or radiotherapy with surgery might contribute to good local control, better PFS, and longer OS.

Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma

BackgroundInformation on the optimal salvage regimen for recurrent esophageal cancer is scarce. We aimed to assess the patterns of locoregional failure, and evaluate the therapeutic efficacy of salvage therapy along with the prognostic factors in recurrent thoracic esophageal squamous cell carcinoma (TESCC) after radical esophagectomy.MethodsA total of 193 TESCC patients who were diagnosed with recurrence after radical surgery and received salvage treatment at our hospital were retrospectively reviewed from 2004 to 2014. The patterns of the first failure were assessed. The post-recurrence survival rate was determined using the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model.ResultsThe median time of failure was 7.0 months. Among the 193 patients, 163 exhibited isolated locoregional lymph node (LN) recurrence and 30 experienced locoregional LN relapse with hematogenous metastasis. Among the 193 patients, LN recurrence was noted at 302 sites; the most common sites included the supraclavicular (25.8%; 78/302) and mediastinal LNs (44.4%; 134/302), particularly stations 1 to 6 for the mediastinal LNs (36.4%; 110/302). The median overall survival (OS) was 13.1 months after recurrence. In those treated with salvage chemoradiotherapy, with radiotherapy, and without radiotherapy, the 1-year OS rates were 68.5, 55.0, and 28.6%; the 3-year OS rates were 35.4, 23.8, and 2.9%; and the 5-year OS rates were 31.8, 17.2, 2.9%, respectively (P < 0.001). Furthermore, patient survival in those who received salvage chemoradiotherapy was significantly better than those treated with salvage radiotherapy alone (P = 0.044). Multivariate analysis showed that the pathological TNM stage and salvage treatment regimen were independent prognostic factors.ConclusionsSupraclavicular and mediastinal LN failure were the most common types of recurrence after R0 surgery in TESCC patients. Salvage chemoradiotherapy or radiotherapy could significantly improve survival in esophageal cancer with locoregional LN recurrence.

The use of Magseed to localise loco-regional lymph node recurrences prior to chemotherapy

Background: Locoregional lymph node recurrence that requires chemotherapy prior to surgery in the setting of no systemic metastases provides oncology dilemmas as to order and type of treatment. In the setting of starting with chemotherapy; localisation of the diseased node prior to treatment is useful as retrieval of diseased nodes post-chemotherapy may prove challenging.

Locoregional Lymph Node Recurrence of Trunk Melanoma in Non-sentinel Lymph Node Basins: An Observational Retrospective Study.

Locoregional lymph node recurrences of primary trunk melanoma can occur in basins not identified during sentinel lymph node biopsy. However, the factors associated with recurrences in non-sentinel lymph node basins are unknown. To evaluate these factors, this observational retrospective study examined the patterns of first lymph node recurrence and the factors associated with recurrence in non-sentinel lymph node basins. A total of 305 patients with primary trunk melanoma who had undergone sentinel lymph node biopsy from 2000 to 2015 were evaluated. Twenty-three patients presented locoregional lymph node recurrence; 8 of which (34.8%) were in non-sentinel lymph node basins. Non-sentinel lymph node recurrences were more frequent in patients with positive sentinel lymph nodes and in those patients whose number of tumour-involved nodes was > 3. These results suggest that clinical examination and ultrasound surveillance should be performed on all potential lymph node drainage basins of trunk melanomas.

Definitive chemoradiation for patients with inoperable and/or unresectable esophageal cancer: locoregional recurrence pattern.

A locoregional recurrence after definitive chemoradiation (dCRT) for patients with inoperable or unresectable esophageal cancer occurs in about 50% of the patients and is a major cause of failure with a poor prognosis. The aim of this study was to determine the pattern of locoregional recurrence and its prognostic factors after dCRT in order to search for improvements in radiation treatment. We retrospectively reviewed 184 patients treated with external beam radiotherapy (50.4 Gray/28 fractions), combined with weekly concurrent paclitaxel and carboplatin. Locoregional recurrences were defined by clinical signs of recurrent or progressive disease, combined with progression on computed tomography/positron emission tomography-computed tomography scan, or suspicious endoscopic findings and/or histological proof of recurrence. The site of locoregional recurrence was analyzed with respect to the borders of the radiation fields. After a mean follow up of 22.8 months, 76 patients (41%) had evidence of locoregional recurrence. The 3-years locoregional recurrence-free rate was 45%. The majority of locoregional recurrences occurred within 12 months, nearly all within 24 months. The majority of these patients failed at the site of the primary tumor (86%). Infield locoregional recurrences at the site of the lymph nodes only occurred in 1% compared with 57% at the site of the primary tumor only. Outfield locoregional lymph node recurrences occurred in 22%, without infield recurrence occurred in only 4% of all patients. The 1-, 3-, and 5-year overall survival was 65%, 28%, and 21%, respectively. The current analysis demonstrates that a locoregional recurrence after dCRT occurs in 41% of the patients, the majority at the site of the primary tumor. These data suggest a benefit of dose intensification of the primary tumor, but not at the site of the lymph nodes. Higher radiation doses should be assessed with prospective trials.

P1-075 - Efficacy and Safety of Chemoradiotherapy for Patients with Locoregional Lymph Node Recurrence of Esophageal Squamous Cell Carcinoma

ABSTRACT Background Although no standard treatment has been established for recurrent esophageal cancer, several studies have suggested the efficacy of chemoradiotherapy (CRT) for the locoregional lymph node recurrence of esophageal squamous cell carcinoma (ESCC). Objective The aim of this study is to evaluate the efficacy and safety of CRT for patients with the locoregional lymph node recurrence of ESCC. Patients and methods Between 2002 and 2009, 167 consecutive patients with thoracic ESCC underwent curative esophagectomy at Shizuoka Cancer Center; of these patients, 41 were diagnosed as locoregional lymph node recurrence. We retrospectively reviewed the data of 30 patients who satisfied the following selection criteria: (i) PS 0–1; (ii) adequate organ function; (iii) no previous radiotherapy (RT) and (iv) concurrent CRT by split regimen (two courses of 5-FU 400 mg/m2 on days 1–5 and 8–12 + CDDP 40 mg/m2 on days 1 and 8 and RT 60 Gy/30 fr for 8 weeks with a 2-week break) or continuous regimen (two courses of 5-FU 700 mg/m2 on days 1–4 + CDDP 70 mg/m2 on day 1 and RT 60 Gy/30 fr for 6 weeks). Results The characteristics of the 30 patients were as follows: median age, 65 years (range: 44–77 ); men/women, 29/1; PS (0/1), 20/10; primary tumor location (upper/middle/lower), 4/19/7; cStage (UICC 6th edition) (I/IIA/IIB/III/IVA/IVB), 1/5/1/17/2/4; adjuvant chemotherapy (+/-), 20/10; site of recurrence (cervical/mediastinal/abdominal/other), 6/20/1/3; number of recurrent lymph nodes (1/ > 2), 18/12. The median time to recurrence from surgery is 11 months (range: 3–57) and 28 patients (93%) completed the planned CRT regimen. The median follow-up period is 25.5 months (range: 6.6–87.7). The complete response rate was 56.7%. The median PFS and the median OS were 9.1 and 22.3 months, respectively. The frequency of grade 3/4 adverse events (CTCAE ver4.0) was as follows: leukocytopenia (30%), neutropenia (23%), anemia (13%), appetite loss (17%) and nausea (7%). No treatment-related deaths occurred. Conclusion CRT is an effective and safe treatment option for the locoregional lymph node recurrence of ESCC.

S-phase fraction and ploidy as predictive markers in primary disease and recurrence of papillary thyroid carcinoma

To investigate the prognostic influence of DNA ploidy and S-phase fraction (SPF) on disease-free (DFS) and overall survival (OS) of patients with primary disease and loco-regional lymph node recurrence of papillary thyroid carcinoma (PTC). A large prospective study with long-term follow-up (median, 117 months). Two series of patients with primary PTC (n = 305) and lymph node recurrence metastasis (LNM) (n = 39) were involved in the study. Patient's age and gender, histological variant, pathological tumour-node-metastasis (pTNM) staging, extrathyroidal extension, vascular and lymphatic invasion and tumour bilateral growth were the clinical and pathological characteristics evaluated. DNA flow cytometry was performed on fresh/frozen surgical tumour samples. Cox regression models were estimated for prognostic analyses. Seventeen (5·6%) primary tumours and five (12·8%) LNMs were aneuploid, while mean SPF was 2·7% and 3·7%, respectively (P = 0·022). High SPF was significantly associated with lymphatic invasion and tall cell and diffuse sclerosing variants. In univariate analysis, all the clinico-pathological variables, but tumour bilateral growth and gender, were significantly correlated with survival. SPF showed borderline significance (P = 0·051) in relation to OS. In multivariate analysis, older age (≥48 years), lymph node spread and high SPF were significantly adverse prognostic factors. Extrathyroidal extension and distant metastasis for OS, as well as tumour size for DFS, were also found as unfavourable prognostic features. In LNM, the Kaplan-Meier curves showed significant differences for older age and DNA aneuploidy (recurrence; P = 0·011). The results indicate that SPF and ploidy can provide additional predictive information in patients with PTC.

Peripheral thyrotropin receptor mRNA as a novel marker for differentiated thyroid cancer diagnosis and surveillance

Thyroid cancer is the most prevalent endocrine cancer whose incidence rates, particularly among women, have increased over the last decade. Although survival outcomes following surgery (with or without radioactive iodine ablation treatment) remain favorable, a significant proportion of patients are at lifetime risk of locoregional lymph node recurrence and distant metastasis. Serum thyroglobulin (Tg) has been the only circulating marker in routine use for detecting thyroid cancer recurrence, but it lacks sensitivity and is unreliable when Tg antibodies are present. New molecular markers for thyroid cancer have been investigated, with most based on detection in thyroid nodule or tumor tissue specimens. Recently, it has become possible to detect thyroid cancer cells in peripheral blood by measuring the mRNA of thyroid-specific genes, such as the mRNA of Tg and thyrotropin receptor. These have become promising new circulating markers for thyroid cancer. This review highlights the progress in this field from the perspective of improved initial cancer diagnosis and enhanced ability to monitor thyroid cancer recurrence.

Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma.

To determine the impact of esophagectomy with 3-field lymphadenectomy on staging, disease-free survival, and 5-year survival in patients with carcinoma of the esophagus and gastroesophageal junction (GEJ). Esophagectomy with 3-field lymphadenectomy is mainly performed in Japan. Data from Western experience with 3-field lymphadenectomy are scarce and dealing with relatively small numbers. As a result, its role in the surgical practice of cancer of the esophagus and GEJ remains controversial. Between 1991 and 1999, primary surgery with 3-field lymphadenectomy was performed in 192 patients, of whom a cohort of 174 R0 resections was used for further analysis. Hospital mortality of the whole series was 1.2%. Overall morbidity was 58%. Pulmonary complications occurred in 32.8%, cardiac dysrhythmias in 10.9%, and persistent recurrent nerve problems in 2.6%. pTNM staging was as follows: stage 0, 0.6%; stage I, 9.2%; stage II, 27.6%; stage III, 28.7%; and stage IV, 33.9%. Overall 3- and 5-year survival was 51% and 41.9%, respectively. The 3- and 5-year disease-free survival was 51.4% and 46.3%, respectively. Locoregional lymph node recurrence was 5.2%; no patient developed an isolated cervical lymph node recurrence. Five-year survival for node-negative patients was 80.2% versus 24.5% for node-positive patients. Five-year survival by stage was 100% in stages 0 and I, 59.1% in stage II, 36.8% in stage III, and 13.3% in stage IV. Twenty-three percent of the patients with adenocarcinoma (25.8% distal third and 17.6% GEJ) and 25% of the patients with squamous cell carcinoma (26.2% middle third) had positive cervical nodes resulting in a change of pTNM staging specifically related to the unforeseen cervical lymph node involvement in 12%. Cervical lymph node involvement was unforeseen in 75.6% of patients with cervical nodes at pathologic examinations. Five-year survival for patients with positive cervical nodes was 27.7% for middle third squamous cell carcinoma. For distal third adenocarcinomas, 4-year survival was 35.7% and 5-year survival 11.9%. No GEJ adenocarcinoma with positive cervical nodes survived for 5 years. Esophagectomy with 3-field lymph node dissection can be performed with low mortality and acceptable morbidity. The prevalence of involved cervical nodes is high, regardless of the type and location of tumor resulting in a change of final staging specifically related to the cervical field in 12% of this series. Overall 5-year and disease-free survival after R0 resection of 41.9% and 46.3%, respectively, may indicate a real survival benefit. A 5-year survival of 27.2% in patients with positive cervical nodes in middle third carcinomas indicates that these nodes should be considered as regional (N1) rather than distant metastasis (M1b) in middle third carcinomas. These patients seem to benefit from a 3-field lymphadenectomy. The role of 3-field lymphadenectomy in distal third adenocarcinoma remains investigational.

Large cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighty-seven cases

Objective: Large cell neuroendocrine carcinoma of the lung is a newly recognized clinicopathologic entity. The clinical characteristics and optimal treatment of patients with large cell carcinomas are not yet established. The aim of this study was to define the clinicopathologic characteristics of large cell neuroendocrine carcinoma. Methods: The histologic characteristics of the patients receiving an initial diagnosis of poorly differentiated non-small cell lung carcinoma (n = 484), small cell carcinoma (n = 55), carcinoid (n = 31), and large cell neuroendocrine carcinoma (n = 12) were retrospectively reviewed according to World Health Organization criteria. Immunohistochemistry was performed to confirm the neuroendocrine phenotype. The outcomes and other clinical characteristics of those patients with large cell neuroendocrine carcinoma were retrospectively analyzed and compared with those of patients with poorly differentiated carcinoma of other histologic types. Results: A total of 87 patients were given a diagnosis of large cell neuroendocrine carcinoma after the histologic review. These patients comprised 3.1% of all patients undergoing resection for primary lung cancer during the same period. The overall 5-year survival was 57%. The 5-year survivals of patients with stage I, II, III, and IV disease were 67%, 75%, 45%, and 0%, respectively. There was no statistically significant difference between the overall survival of patients with large cell neuroendocrine carcinoma and those with other non-small cell lung cancers. There was a significant difference between the survival of patients with stage I large cell neuroendocrine carcinoma and that of patients with the same stage of other non-small cell lung carcinomas. The site of the first documented recurrence was locoregional in 12 patients (34%), distant metastases in 20 patients (57%), and both simultaneously in 3 patients. Locoregional lymph node recurrences were observed frequently. More than 80% of recurrences were found within 1 year after the operation. Conclusion: In terms of prognosis, large cell neuroendocrine carcinoma is distinctly different from other non-small cell lung cancers. The prognosis of large cell neuroendocrine carcinoma was poor, even for early stage disease; the prognosis of the stage I disease of large cell neuroendocrine carcinoma was poorer than that of the same stage of other non-small cell lung cancers. Because of its aggressive clinical behavior and poor prognosis, large cell neuroendocrine carcinoma should be recognized as one of the poorest prognostic subgroups among primary lung cancers, and therefore novel therapeutic approaches should be established.J Thorac Cardiovasc Surg 2002;124:285-92