Regional Node Recurrence Research Articles

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC). This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil. The median age of the patients was 70years (range 52-83years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66Gy (range 50.4-66Gy). The median follow-up period for the survivors was 71months (range 8-175months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment. The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events.

Representativeness of initial skin biopsies showing pure desmoplastic melanoma: implications for management

Desmoplastic melanoma (DM) is an uncommon subtype of melanoma with distinct clinicopathological features. It is classified into pure desmoplastic melanoma (PDM) when the proportion of desmoplastic melanoma is ≥90% of the dermally-invasive component, and mixed desmoplastic melanoma (MDM) when the proportion of desmoplastic melanoma is <90%. Studies have reported a lower sentinel lymph node biopsy (SLNB)-positivity rate in PDM compared to MDM and non-DM. As a result, some have recommended not performing SLNB in PDM patients. When PDM is identified in a partial biopsy of a melanoma, there is a risk that sampling bias may under-recognise MDM, but to the best of our knowledge this has not been previously assessed or quantified. The aim of this study was to assess the concordance of the proportion of desmoplastic melanoma in an initial partial biopsy of PDM with the proportion in the entire tumour following complete excision, in patients with cutaneous melanoma. A secondary aim was to determine how frequently this potentially resulted in a patient not receiving a SLNB. Seventy-eight cases of cutaneous melanoma were identified from the Melanoma Institute Australia (MIA) database and 23 cases from the Memorial Sloan Kettering Cancer Centre (MSKCC), where an initial biopsy contained PDM and a subsequent wide excision had residual invasive melanoma. Clinicopathological features were analysed in all patients, including whether a SLNB was performed, the results of SLNB, and any subsequent recurrence. Ninety percent (91/101) of cases were still classified as PDM in the complete wide excision specimen while 10% (10/101) of cases were reclassified as MDM, which was a significant change in classification of final desmoplastic melanoma subtype (p<0.001). The proportion of desmoplastic melanoma was also significantly different between the initial and excisional biopsies (p=0.004). Forty-eight (48/101) patients had a SLNB, of which two (4.5%) were positive for metastatic melanoma; both cases were PDM in the excision specimen. Of the 10 cases demonstrating MDM in the excision specimen, the initial biopsy was a punch biopsy in six cases, shave biopsy in two cases and subcutaneous tissue was sampled in two patients (one punch biopsy, one incisional biopsy). Four of these 10 patients underwent SLNB which was negative in all cases. Twenty-two patients developed recurrence in the follow-up period (median 30 months, range 1-192 months), three with MDM in their excision specimen. One patient did not have a SLNB and developed regional lymph node recurrence. In this study there was a 10% risk that the percentage of desmoplastic melanoma in an initial biopsy of PDM was not representative of the entire lesion, resulting in reclassification as MDM in the excision specimen. If a SLNB is not performed in such cases, a positive SLNB may be missed (one patient in our study) which could impact treatment options for the patient. We recommend caution in not offering a SLNB in the setting of an initial biopsy of PDM if the biopsy is small compared with the overall lesion. If a SLNB is not procured at the time of wide excision in such cases, the SLNs should still be mapped by lymphoscintigraphy to facilitate careful follow up and to enable earlier detection and treatment of nodal disease.

Significance of dissection in each regional lymph-node station of esophageal cancer based on efficacy index and recurrence patterns after curative esophagectomy.

The optimal extent of lymph-node (LN) dissection in esophageal cancer has not been established. Although the frequency and patterns of recurrence in each regional LN station after radical dissection are important in determining the regional LNs of thoracic esophageal cancer to be routinely dissected, this information has not been investigated sufficiently. We studied the significance of dissection at each LN station based on their recurrence patterns. Six hundred and twelve patients with esophageal cancer who underwent curative esophagectomy were studied. The incidence and pattern of recurrence (systemic or non-systemic) at each regional LN station were analyzed. To compare the significance of dissection among regional LNs, the efficacy index (EI) was also calculated. Regional LN recurrence was diagnosed in 101 (16.5%) patients. Among the regional LNs, recurrent laryngeal nerve, paraesophageal, and perigastric LNs showed higher EIs (3.1-6.7). Pretracheal and posterior thoracic para-aortic LNs showed low EIs (0-0.2). Supraclavicular LNs had moderate EIs (1.7-2.0). The recurrence rate was highest in the pretracheal LN, followed by the supraclavicular LNs. The majority (81.8%) of the pretracheal LN had a systemic recurrence, while about half (right: 60.0%, left: 43.8%) of the supraclavicular LNs had a systemic recurrence. Due to the high incidence of systemic recurrence or low EI for pretracheal and posterior thoracic para-aortic LNs, we suggest that these LN stations be regarded as non-regional LNs and be excluded from routine dissection. Supraclavicular LNs may also be excluded from routinely dissected stations.

194 (PB-107) Poster - Retrospective thorough analysis of regional lymph node recurrence in breast cancer patients (REASON Trial)

Background: De-escalation of axillary surgery reduces morbidities without altering survival. Despite of a relatively high rate of residual disease in the axilla after sentinel lymph node (SLN) procedure, the risk of regional lymph node recurrence (RLNR)is very low, due probably to adjuvant radiotherapy and systemic treatments. The characteristics of the small percentage of patients with RLNR are not well known. We performed a retrospective thorough analysis of patients with RLNR.

PP05 Presentation Time: 9:40 AM: 21 Gy Single Fraction Prostate HDR Brachytherapy: Mature Results of a Single Institution Prospective Study.

<h3>Purpose</h3> To present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. <h3>Materials and Methods</h3> Patients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients with prostate volumes > 50 cc or <12 cc, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association (AUA) symptom scores > 12 were ineligible. Patients underwent trans-rectal ultrasound (TRUS)-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy. Treatment was delivered via Ir-192 to a dose of 21 Gy, prescribed to the prostate with no additional margin applied. Treatment planning was TRUS-based with constraints as follows: prostate V100 > 95%; urethral V115 < 1%; rectal V72 ≤ 1% prescription dose. <h3>Results</h3> A total of 26 patients were enrolled. Median follow up was 4.0 years (range 0.6-5.7 years). Median age was 64 years. Median gland volume at the time of treatment was 41 cc. 88.5% of patients had T1 disease, 15.4% had Gleason score 6, 84.6% Gleason score 7, and median pre-treatment PSA was 5.0 (range 2.7-12.2) ng/mL. Acute and chronic grade 2 GU toxicity rates were 26.9% and 38.5%, respectively. Acute grade 3 GU toxicity rate was 11.5%. There were no chronic grade 3 GU toxicities. There were no grade 2+ acute or chronic GI toxicities. The 5-year biochemical failure rate was 35.1%. The 5-year radiographic local failure rate was 32.4%. Biopsy-proven local failure at 5-years was 15.3%. Two patients underwent salvage treatment after experiencing radiographic local failure, without an attempted biopsy of the prostate. No patients developed biopsy proven or radiographic regional lymph node recurrence or distant metastasis. 5-year overall survival was 96.2%. The single patient death was a result of a myocardial infarction approximately 7 months after protocol treatment. Cause-specific survival at 5 years was 100%. <h3>Conclusions</h3> Despite being well-tolerated, 21 Gy single fraction HDR brachytherapy is associated with high biochemical and local failure rates. The results from this prospective pilot study do not support continued investigation of this dosing regimen in subsequent investigation.

Adenoid Cystic Carcinoma of the Head and Neck: Patterns of Recurrence and Implications for Radiotherapy

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) plays a central role in locoregional control for adenoid cystic carcinoma of the head and neck (ACC). Guidelines on the optimal RT dose, treatment volumes, and modality are lacking in the highly conformal era. We sought to evaluate ACC patterns of recurrence to assess the efficacy of highly conformal RT and optimize target volumes and dose. <h3>Materials/Methods</h3> We identified all patients with ACC consecutively treated at our institution with curative-intent adjuvant or definitive RT from 2005 to 2021 and recorded local (LR) and distant metastasis (DM) events. RT plans were compared to diagnostic imaging to identify in-field, out-of-field, and marginal LRs. Marginal LRs were defined as those within the 50 Gy isodose line but outside of the CTV. <h3>Results</h3> Ninety-nine patients were included. Median follow-up was 5.1 years (IQR: 2.2-9.0). Eighty (80.8%) patients underwent surgery prior to RT. Dose was <60 Gy (10, 10.1%), 60 Gy (49, 49.5%), >60/<70 Gy (19, 19.2%), or 70 Gy (21, 21.2%). CTVs included at least one lymph node level in 61 (61.6%) patients. CTVs tracked along cranial nerves (CN) in 67 (67.7%) patients, with 61 (61.6%) receiving RT to CN V and 43 (43.4%) to CN VII. CN were tracked to the skull base and brainstem in 46 (46.5%) and 21 (21.2%) patients, respectively. Thirty-one (31.3%) patients received intensity modulated proton therapy, with the remainder (68, 68.7%) receiving photon-based intensity modulated radiation therapy. The 2- and 5-year LR risk was 3.6% (95% CI: 1.2-10.9) and 12.2% (6.6-22.7). Predictors of LR on univariate analysis included nasal cavity/nasopharynx location [HR 7.30 (1.17-45.66), <i>p</i>=.034] and primary tumor volume [per 10 cc, HR 1.44 (1.05-1.97), <i>p</i>=.023]. All other factors including concurrent chemotherapy and proton therapy were not associated. Although prescribed RT dose was not significant, 7 of the 10 patients with in-field LRs received ≤60 Gy [50 Gy (n=1), 54 Gy (n=1), 56 Gy (n=1), 60 Gy (n=4)]. Only 2 patients experienced a marginal LR, one with an oral cavity primary that recurred in the mandible bone, and the other with a submandibular primary that recurred in the oropharyngeal mucosa. Only 1 patient each had an out-of-field LR and regional nodal recurrence. Six of the 7 patients with a skull base recurrence (SBR) had coverage of CN to the skull base (n=3) or brainstem (n=3). Six recurred in a treated CN (in-field), and the other recurred in an untreated CN (out-of-field). DM risk was 26.9% (18.9-38.2) and 44.0% (33.8-57.3) at 2- and 5-years, respectively. Median overall survival was 9.2 years. <h3>Conclusion</h3> Modern conformal RT provides excellent locoregional control for patients with ACC. Marginal and out-of-field LRs are rare, validating the use of intensity modulated RT, including proton therapy. Given a low rate of regional nodal recurrence, elective nodal coverage may be omitted in well-selected patients. SBR, while uncommon, occurs primarily in those receiving skull base RT, suggesting a potential role for dose escalation in high-risk patients.

A PI3Kinase/Akt/mTOR Gene Expression Signature Predicts for Recurrence in Early-Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) has emerged as an effective alternative to surgery in the treatment of early-stage non-small cell lung cancer (NSCLC). Despite this, disease progression occurs in over 20-30% of patients. Previous work established AKT/mTOR signaling as a pathway modulating response to radiation for NSCLC. In this study, we sought to validate a previously published mRNA signature that measures PI3K/Akt/mTOR pathway activation and measure its association with clinical outcomes in patients with early-stage NSCLC treated with SBRT. <h3>Materials/Methods</h3> We queried our institutional dataset for patients with T1-3N0 NSCLC treated with SBRT. RNA of formalin fixed paraffin embedded biopsy specimens (pre-therapy) was isolated and mRNA expression was analyzed using the Clariom D^TM assay. We derived a t score, defined as the two-sided t statistic comparing the average of the PI3K-induced genes with that of repressed genes within each tumor after centering log-transformed values on the median across samples. Cox proportional hazards was performed to account for age, sex, ECOG performance status, biological effective dose, and histology. <h3>Results</h3> We identified 92 patients with NSCLC treated between 2008 and 2018 with available gene expression and dichotomized patients by their median PI3K pathway score (<i>Table 1</i>). Median follow up was 24.0 months. Higher PI3k score was associated with worse progression-free survival (PFS) (HR= 3.98; 95% CI 1.57–10.09; p=0.0035) and local recurrence (LR) (HR= 11.72; 95% CI 1.40–98.0; p=0.023). There was no significant association with overall survival (p=0.49), regional nodal recurrence (p=0.15), or distant recurrence (p=0.85). On multivariable analysis, PI3K score remained independently associated with worse PFS (HR= 3.03; 95% CI 1.13–8.13; p=0.028) and LR (HR= 17.15; 95% CI 1.50–195.59; p=0.022). Worse performance status (HR= 2.58; 95% CI 1.06–6.27) and younger age (HR= 0.94; 95% CI 0.88–0.999) were also associated with worse PFS. <h3>Conclusion</h3> Our findings demonstrate that degree of PI3K pathway activation is associated with PFS and LR after SBRT for early-stage NSCLC. This requires validation in an independent dataset but may be useful in prognostication or in selecting patients for treatment intensification.

Patterns of Regional Lymph Node Recurrence after Surgery for Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma: A Retrospective Analysis in a Single Institution

<h3>Purpose/Objective(s)</h3> The overall incidence of cholangiocarcinoma (CCA) has increased progressively worldwide over decades. CCAs are highly aggressive, which renders a dismal prognosis with high recurrence rates after dissection and disappointing 5-year survival rate (7%-20%). Surgical resection remains the mainstay of potentially curative therapy for intrahepatic CCA (iCCA) or combined hepatocellular carcinoma (HCC)-CCA. Most patients develop recurrent disease after surgery and extrahepatic recurrence was found in 40% patients. Postoperative radiotherapy (RT) has been considered an adjuvant treatment modality. However, no consensus has been reached regarding to the clinical target volume (CTV) of RT. We aim to investigate the patterns of regional recurrence after surgery for iCCA and combined HCC-CCA to give insights on CTV delineation. <h3>Materials/Methods</h3> Medical records of iCCA and combined HCC-CCA patients who underwent surgery at Cancer Hospital of Chinese Academy of Medical Sciences between 2010 to 2019 were retrospectively reviewed. Patients were included in this study if they 1) had been pathologically diagnosed with iCCA or combined HCC-CCA; 2) underwent surgical resection; and 3) had been diagnosed with first recurrent event in regional LNs. Patients were excluded if they had adjuvant radiotherapy. All available follow-up imaging studies were thoroughly reviewed. Patterns of recurrence were categorized as local (intrahepatic), regional (regional LNs) and distant failure. Regional failures as first site of recurrence were further evaluated. <h3>Results</h3> A total of 53 patients were included in analysis, 42 of which had iCCA and 11 had combined HCC-CCA. The median age was 59 years (35-70) for all patients. The proportion of patients with history of hepatitis B and elevated AFP was higher in combined HCC-CCA group than in iCCA group. 67.9% patients underwent R0 resection and the median number of dissected LNs is 5 (0-31). Hepatic hilar is the most common recurrent region for both groups followed by portal vein-vena cava (high risk stations). Recurrence rates at left gastric, paracardial, diaphragmatic, common hepatic, celiac trunk and superior mesenteric artery are similar and moderate (medium risk stations). There is much less recurrence at other LN regions with likelihood less than 10% (low risk stations). A total of 20.8% patients had skip metastases. 13.2% patients had recurrence at medium risk stations without recurrence at high-risk stations and 7.6% patients had recurrence at high and low risk stations without recurrence at medium risk stations. A figure of 3-dimentional distribution of recurrent LNs was created. A standard patient was selected and all recurrent LNs were contoured on her CT images according to relationship between LNs and vessels. <h3>Conclusion</h3> This study created a LN recurrence map of surgically resected iCCA and combined HCC-CCA patients, which might be helpful for radiation oncologists in CT-guided delineation of postoperative CTV.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy

BackgroundTo review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT).MethodsFrom April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28–30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.ResultsAmong the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153).ConclusionDistant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

ASO Visual Abstract: Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

ASO Visual Abstract: Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma

Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Nodal observation with ultrasonography rather than CLND. In-basin nodal recurrence. Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. ClinicalTrials.gov Identifier: NCT00297895.

Mode of Detection of Second Events in Routine Surveillance of Early Stage Breast Cancer Patients

IntroductionNCCN and ASCO guidelines recommend breast cancer (BC) follow-up to include clinical breast examination (CBE) every 6 months and annual mammography (AM) for 5 years. Given limited data to support CBE, we evaluated the modes of detection (MOD) of BC-events in a contemporary practice. MethodsWe conducted a retrospective review of registry patients with early stage BC (DCIS, Stage I or II) diagnosed between 2010 and 2015 with at least 5 years of follow-up. Second events were defined as malignant (contralateral primary, ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, regional node recurrence or distant relapse) or benign. MOD was categorized as patient complaint, clinical examination or breast imaging. ResultsSixty-three of 351 BC patients experienced second events. 15 had BC malignant events, including 4 distant disease, 5 contralateral primary, and 3 IBTR. 7/8 of IBTR and contralateral primary BC were AM detected. Patient complaints identified 4/4 distant relapses. Clinical exam identified 2/2 chest wall recurrences in post-mastectomy patients. ConclusionsOnly 2.8% (10/351) of early stage BC patients experienced recurrence during 5 years of follow-up. AM was the predominate MOD of both IBTR and new contralateral primary following breast conserving therapy. Patient complaints prompted evaluation for distant disease. Provider CBE was MOD in only 2/351, 0.6% 95% CI (2.1%-0.1%) of patients as chest wall recurrences postmastectomy. Given modern enhancements to imaging and lower recurrence rates, this data encourages the reassessment of guidelines for every 6-month CBE and provides basis to study telehealth in survivorship care.

P-238 Pattern of failure after radiotherapy for squamous cell carcinoma of the anus

Squamous cell carcinoma of the anus (SCCA) is primarily treated with radiotherapy (RT). Treatment failure is predominantly locoregional within the pelvic area. Information on the pattern of failure is important when optimizing treatment strategies. The aim of this study was to evaluated pattern of failure and outcome after radiotherapy for SCCA. A single center, retrospective study was conducted, including patients with histopathological proven SCCA diagnosed between 1998 and 2018 and treated with RT with curative intention. Data was collected from medical records and included patient-, disease-, and treatment characteristics, and outcome data. Disease stage was reclassified according to the 8th edition of the TNM staging system. Locoregional failure (LRF) was defined as failure within the pelvis, and distant failure (DF) as failure outside the pelvis. Survival data were estimated using the Kaplan-Meier method. In total 420 patients treated with curative RT were identified. Median age was 60 years (range 28-89), 75.0% were female, 68.8% had T1-T2 tumors, and 30.9% were diagnosed with lymph node (LN) positive disease. All patients received RT, RT only (79.8%) or with concomitant chemotherapy (19.3%), further 30.7% received induction chemotherapy. Treatment planning was done with IMRT/VMAT in 76.4% of cases, and median prescribed dose to tumor was 64Gy (range 45-64), 64Gy (range 50-64) to pathological LN and 51.2Gy (range 39-54) to the elective nodal areas. Median follow-up (FU) time was 6.1 years (range 0.05-23.6). Overall survival for all stages at 3- and 5 years was 84.0% and 75.5%, respectively and disease-free survival was 73.2% and 69.9% at 3 and 5 years. 85.9% (n=361) achieved complete response (CR) after RT whereas 13.8% (n=58) was diagnosed with progressive or persistent disease, of whom 94.8% had salvage surgery performed. Of patients with CR after RT 19.1% (n=69) experienced treatment failure during FU. As first site of recurrence 13.0% had LRF (n=47), 5.0% had DF (n=18), and 1.1% had both LRF and DF (n=4). When combining both persistent disease and later recurrence 30.2% experience treatment failure. In general, few regional LN recurrences were observed (1.7% of first failures including 0.6% with LN only failures). Recurrence in regional LN was located to the mesorectal LN (n=2), inguinal LN (n=3) or iliac LN (n=1). DF as first site of failure was seen in 22 cases (6.1%) located to either the lung (n=11), liver (n=7) distant LN (n=8), bone (n=1), brain (n=1) or other (n=2) with 8 patients having failure to more than one site. When looking at subsequent failures DF was seen in further 14 cases with a total DF rate of 8.6%. Recurrences to regional LN and DF were low, and the majority of recurrences were thus located within the standard irradiated area. Consequently, it is highly relevant to investigate the exact anatomical location and its relation to specific treatment dose. A dose-mapping study is therefore ongoing.

Racial/ethnic disparities in locoregional recurrence in hormone-receptor positive node-negative breast cancer patients enrolled in the TAILORx trial.

515 Background: Whether racial/ethnic disparities in locoregional recurrence (LRR) exist in patients (pts) with similar access to care treated on clinical trials is uncertain. We examined racial/ethnic differences in LRR in hormone-receptor positive HER2-negative (HR+HER2-) node-negative pts enrolled in the TAILORx trial. Methods: 10,273 pts age 18-75 were enrolled in TAILORx, which assigned pts with an OncotypeDx Recurrence Score (RS) &lt;11 to endocrine therapy (ET) alone, those with RS &gt;25 to chemotherapy + ET (CET), and randomized pts with RS 11-25 to ET or CET. Pts with unknown race/ethnicity (n=323) or incomplete treatment adherence information (n=1,168) were excluded from this analysis. Race/ethnicity was self-reported. LRR was defined as ipsilateral invasive in-breast, chest wall, or regional nodal recurrence without distant recurrence. Kaplan-Meier curves were used to estimate 8-year LRR. Cox proportional hazards analysis adjusted for clinical and treatment factors was used to determine factors associated with LRR. Results: 8,782 pts with T1-2N0 HR+HER2- breast cancer were included. Race/ethnicity was non-Hispanic White (NHW) in 6,932 (78.9%), non-Hispanic Black (NHB) in 629 (7.2%), Hispanic in 818 (9.3%), and Asian in 403 (4.6%). Treatment adherence was high across groups over time, with a 9.1% crossover in treatment arms. Average duration of ET was 63.8 +/- 0.3 months. Radiation therapy was planned in 96.0% of pts after breast conservation and 12.7% after mastectomy. At a median follow-up of 8 years, LRR rates were 1.9% in NHW, 4.2% in in NHB, 3.2% in Hispanic, and 3.9% in Asian pts (p&lt;0.01). LRR rates broken down by RS are shown in the Table. On adjusted analyses, NHB and Asian (vs. NHW) pts were more likely to have LRR (HR 1.94 for NHB, HR 2.04 for Asian, p&lt;0.05 for both). Additional statistically significant factors associated with LRR included age &lt;50 (HR 1.85), T2 tumors (HR 1.43), higher grade (HR 2.30 for grade 3), and high RS (HR 3.13 for RS&gt;25). Treatment receipt (chemotherapy, ET duration, and radiation) was not associated with LRR in this population. Conclusions: Racial/ethnic differences in LRR were seen in T1-2N0 HR+HER2- breast cancer pts enrolled in the TAILORx trial despite high rates of treatment adherence in this clinical trial population, with highest LRR rates in NHB and Asian pts. Further study in needed to understand racial/ethnic patterns in LRR by breast cancer subtype and if failure to rescue after LRR may contribute to differences in breast cancer mortality.[Table: see text]

The impact of lymphadenectomy on lymph node recurrence after performing various treatments for esophageal squamous cell carcinoma

BackgroundTreatment for regional lymph node recurrence after initial treatment for esophageal squamous cell carcinoma (ESCC) differs among institutions. Though some retrospective cohort studies have shown that lymphadenectomy for cervical lymph node recurrence is safe and leads to long-term survival, the efficacy remains unclear. In this study, we investigated the long-term outcomes of patients who underwent lymphadenectomy for regional recurrence after treatment for ESCC.Patients and methodsWe retrieved 20 cases in which lymphadenectomy was performed for lymph node recurrence after initial treatment for ESCC in our hospital from January 2003 to December 2016. Initial treatments included esophagectomy, endoscopic resection (ER) and chemoradiotherapy/chemotherapy (CRT/CT). Overall survival (OS) and recurrence-free survival (RFS) after lymphadenectomy were calculated by the Kaplan–Meier method. We also used a univariate analysis with a Cox proportional hazards model to determine factors influencing the long-term outcomes.ResultsThe five-year OS and RFS of patients who underwent secondary lymphadenectomy for recurrence after initial treatment were 50.0% and 26.7%, respectively. The five-year overall survival rates of patients who received esophagectomy, ER and CRT/CT as initial treatments, were 40.0%, 75.0% and 50.0%, respectively. The five-year OS rates of patients with Stage I and Stage II-IVB at initial treatments were 83.3% and 33.3%, respectively.ConclusionsLymphadenectomy for regional recurrence after initial treatment for ESCC is effective to some degree. Patients with regional recurrence after initial treatment for Stage I ESCC have a good prognosis; thus, lymphadenectomy should be considered for these cases.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Radioisotope-Guided Sentinel Lymph Node Biopsy in Penile Cancer: A Long-Term Follow-Up Study.

Lymph node (LN) management is critical for survival in patients with penile cancer. However, radical inguinal lymphadenectomy carries a high risk of postoperative complications such as lymphedema, lymphocele, wound infection, and skin necrosis. The European Association of Urology guidelines therefore recommend invasive LN staging by modified inguinal lymphadenectomy or dynamic sentinel node biopsy (DSNB) in clinically node-negative patients (cN0) with intermediate- and high-risk tumors (≥ T1G2). However, the timing of DSNB (simultaneous vs. subsequent to partial or total penile resection) is controversial and the low incidence of penile cancer means that data on the long-term outcomes of DSNB are limited. The present study aimed to analyze the reliability and morbidity of DSNB in patients with penile cancer during long-term follow-up. This retrospective study included 41 patients (76 groins) who underwent radioisotope-guided DSNB simultaneously or secondarily after penile surgery from June 2004 to November 2018. In total, 193 sentinel LNs (SLNs) and 39 non-SLNs were removed. The median number of dissected LNs was 2.5 (interquartile range 2–4). Histopathological analysis showed that five of the 76 groins (6.6%) contained metastases. None of the non-SLNs were tumor-positive. In accordance with the guidelines, all inguinal regions with positive SLNs underwent secondary radical inguinal lymphadenectomy, which revealed three additional metastases in one groin. Regional LN recurrence was detected in three patients (four groins) during a median follow-up of 70 months, including two patients in whom DSNB had been performed secondarily after repetitive penile tumor resections. DSNB-related complications occurred in 15.8% of groins. Most complications were mild (Clavien–Dindo grade I; 50%) or moderate (II; 25%), and invasive intervention was only required in 3.9% of groins (IIIa: n = 1; IIIb: n = 2). In summary, this study suggests that the current radioisotope-guided DSNB procedure may reduce the complication rate of inguinal lymphadenectomy in patients with cN0 penile cancer. However, DSNB and penile surgery should be performed simultaneously to minimize the false-negative rate. Recent advances, such as new tracers and imaging techniques, may help to reduce the false-negative rate of DSNB further.

Impact of Regional Lymph Node Irradiation on Reducing Lymph Node Recurrence in Esophageal Cancer Patients.

To evaluate the preventive effects of regional lymph node irradiation on lymph node recurrence in esophageal cancer (EC). The study included 289 patients who received definitive radiotherapy for EC. The regional lymph node area of group 1 was determined as the area with the highest probability of lymph node metastasis and group 2 was determined as the area with the next highest probability of lymph node metastasis depending on the primary site of EC. The patients in whom group 2 was completely included in the irradiated field had a significantly lower rate of recurrence of regional lymph node metastasis than those in whom group 2 was not or insufficiently included (p=0.0337). There was no significant difference in overall survival (p=0.4627) or disease-specific survival (p=0.6174) between the two groups. Regional lymph node irradiation did not have survival-prolonging effects but significantly reduced regional lymph node recurrence.

Preliminary application of transoral robotic thyroidectomy: experience from an initial 30 cases

Objective: To examine the surgical outcome of transoral robotic thyroidectomy. Methods: Clinic data of total 30 cases of transoral robotic thyroidectomy at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from May 2020 to December 2020 were analyzed retrospectively. There were 3 males and 27 females, aged (31.5±11.0) years (range: 17 to 55 years), including 6 cases of benign tumor and 24 cases of malignant cancer (all papillary thyroid carcinoma). An inverted U-shaped incision 1.5 cm in length was made over the end of the frenulum of the lower lip. A wide subplatysmal space was created by bluntly passing with a vascular tunneller (8 mm diameter), and a 12 mm trocar was inserted through the lip incision for the camera port. Lateral oral mucosal incisions 8 mm in length were made near both lateral labial commissures, 8 mm robot trocars were inserted through the incisions. An 5 mm trocar was inserted through an incision made along the patient's right axillary fold into the subplatysmal working space and was connected with 5 mm ProGrasp for counter traction during the operation and for later drain insertion. Numerical scoring system (NSS) was used to assess cosmetic effect 1 month post-operation. Results: All the 30 transoral robotic thyroidectomies was successful, no case conversed to open operation. Postoperative hospital stay was (6.3±1.2) days (range: 4 to 10 days). The tumor size of thyroid cancers was (5.3±3.0) mm (range: 2 to 15 mm). Lymph node metastasis was observed in 12 cases. The retrieved central lymph node number was 10.5±4.4 (range: 4 to 20), while the central metastatic lymph node number was 2(2) (range: 1 to 11). Postoperative transient hypoparathyroidism occurred in 2 cases. Permanent hypoparathyroidism and vocal cord palsy didn't occur. Other surgical complications included hematoma, surgical site infection and perforation of chin flap, retrospectively in 1 case. Local regional lymph node recurrence wasn't developed during 1 to 7 months follow-up. All patients were satisfied with the postoperative cosmetic outcomes,NSS was 9.4±0.8 (range: 8.7 to 9.6). Conclusion: Transoral robotic thyroidectomy is safe and effective, suitable for early thyroid cancers without lateral lymph node metastasis, and has superior cosmetic results when the patients are selected carefully.

Outcomes of 1 000 cases of robotic thyroidectomy by bilateral axillo-breast approach: a retrospective study in a single center

Objective: To examine the surgical outcome, completeness and safety of robotic thyroidectomy by bilateral axillo-breast approach (BABA). Methods: From February 2014 to May 2019, 1 000 cases of robotic thyroidectomy via BABA at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army were performed. The clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes of patients underwent robotic thyroidectomy were collected and reviewed retrospectively. There were 216 males and 784 females, aging (42.3±11.5) years (range: 7 to 75 years). There were 270 cases with benign tumors, and 730 cases with malignant cancers (the tumor diameter was (7.9±6.7) mm (range: 0.1 to 60.0 mm)). Results: There were 999 patients received robotic thyroidectomy using BABA approach successfully, while only 1 case conversed to open operation. The postoperative hospital stay was (7.5±2.5) days (range: 2 to 30 days). Among the 730 patients with thyroid cancers, 725 cases (99.3%) were papillary thyroid carcinoma, 579(79.3%) cases were with papillary thyroid microcarcinoma. Lymph node metastasis was observed in 371(50.8%) cases. The retrieved central lymph node number was 11.2±6.1 (range: 1 to 44),and the retrieved lateral lymph node number was 14.0±8.8 (range: 1 to 52). Postoperative transient hypoparathyroidism and vocal cord palsy occurred in 247(24.70%) and 56(5.60%) cases. Both of permanent hypoparathyroidism and vocal cord palsy occurred in 2 (0.20%) cases. Other surgical complications included chyle leakage (6.1%, 28/460), trachea injury (0.40%, 4/1 000), carotid artery injury (0.10%, 1/1 000). Local regional lymph node recurrence was developed in 4 patients. All patients were satisfied with the postoperative cosmetic outcomes. Conclusions: Robotic thyroidectomy by BABA is safe and effective, suitable for large benign tumors and early thyroid cancers with central or lateral lymph node metastasis. It could obtain superior cosmetic results.