Supraclavicular Nodes Research Articles

OGC P57 Are Cervical Lymph Node Dissections in Oesophageal Cancer Patients Undergoing Oesophagectomy Beneficial?

Abstract Background Cervical lymph node dissection in patients undergoing oesophagectomy can be indicated when there is suspicion of involved cervical nodes, although there is controversy around the benefits of this additional procedure on the prognosis of these patients. This study aims to assess the consequences and survival after cervical lymph node dissection, and to weigh the risks and benefits of this procedure. Methods This retrospective study included seven patients with oesophageal squamous cell carcinoma (SCC), and one with oesophageal adenocarcinoma who underwent cervical lymph node dissection in addition to oesophagectomy at the Churchill Hospital. There was a male to female ratio of 1:3, and all had neoadjuvant chemotherapy and were staged with PET-CT. PET staging scan results were compared pre and post neo-adjuvant therapy (NAT) to assess nodal involvement. Final histopathology was also recorded. Results All patients had evidence of cervical nodal involvement on PET scan, two of whom developed nodal involvement only after NAT. Only two patients had neck node involvement on histopathology: one had SCC and showed good response to NAT; the other had undifferentiated carcinoma and showed new para-tracheal node involvement after NAT, later developing supraclavicular node recurrence. Two cases were complicated by recurrent laryngeal nerve (RLN) injury, one with bilateral and one with partial vocal cord palsy. There was a 5-year survival rate of 62.5%, with non-survivors uniquely having recurrent disease. Conclusions Lymph node dissection alongside oesophagectomy achieved good 5-year survival in this small cohort, but with a significant risk of RLN injury. Further studies investigating the proportion of metastatic neck nodes found on dissection, long term survival benefits and cancer reoccurrence are required.

NCMP-21. AQP4-MOG DOUBLE-POSITIVE PARANEOPLASTIC NEUROLOGICAL SYNDROME IN A PATIENT WITH TRIPLE NEGATIVE BREAST CANCER

Abstract We report a rare case of paraneoplastic neurological syndrome (PNS) with dual seropositivity of anti-aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) antibodies in a 40 year-old lady with metastatic triple negative breast cancer with involvement of mediastinal, right axillary, and supraclavicular lymph nodes. She received multiple lines of anti-neoplastic treatment including immunotherapy with pembrolizumab as well as chemotherapy with taxol, carboplatin, gemcitabine, capecitabine, cytoxan, sacituzumab and nevalbine. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis extending from T11-12 that symptomatically improved with high dose intravenous methylprednisolone. One month later she developed left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid (CSF) analysis during both episodes revealed normal glucose, protein, elevated white blood cell count. Cytology was negative for malignancy. CSF was positive for neuromyelitis optica (NMO) IgG antibody APQ-4 and autoimmune myelopathy panel was positive for MOG antibody. Patient had significant clinical and radiographic improvement after completion of plasmapheresis and intravenous immunoglobulin. There was resolution of pleocytosis on repeat CSF testing. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every six months and daily low dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case demonstrates that these antibodies can occur concurrently and cause clinical features like both neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or CSF profile negative for leptomeningeal carcinomatosis.

Outcomes and Prognostic Analysis of Surgical Resection for Oligometastasis from Hepatocellular Carcinoma.

This study aimed to evaluate the outcomes of patients who underwent resection for oligometastasis from hepatocellular carcinoma (HCC) and identify the prognostic factors associated with poor survival. Patients who underwent resection for oligometastasis from HCC between January 2000 and April 2021 were retrospectively investigated. Oligometastasis was defined as 1-5 single organ metastases that were detected preoperatively in this study. Clinical characteristics and treatment outcomes were analyzed, and independent risk factors for poor prognosis were identified using cox proportional hazards model. A total of 33 patients were included in this study. Eleven oligometastases were located in the intraabdominal lymph node, 8 in the adrenal gland, 5 in the lung, 4 in the peritoneum, 3 in the pleura, and 1 each in the supraclavicular lymph node and abdominal wall. No re-operation or operative death occurred in this study. The median OS was 44.6 months (range=5.1-150.6 months), and the median survival after primary HCC diagnosis was 116.5 months (range=7.1-253.6 months). The median cumulative incidence of recurrent HCC was 7.2 months (range=0.3-94.7 months). The multivariate analysis showed that an alpha-fetoprotein level ≥20 ng/ml and multiple primary HCC tumors were independent poor prognostic factors. Clinical characteristics and treatment outcomes of patients who underwent resection for oligometastasis from HCC were demonstrated. A high alpha-fetoprotein level and multiple primary HCC tumors were independent poor prognostic factors. Surgical resection can be one of the treatment options for oligometastasis from HCC.

Diagnostic dilemma of the supraclavicular lymph node in oncology.

Diagnostic dilemma of the supraclavicular lymph node in oncology.

False-positive supraclavicular lymph node detected on chest computed tomography in oncology patients: Clinical implication based on subsequent neck ultrasonography and ultrasonography-guided tissue sampling.

The purpose of this study was to assess the prevalence and clinical implications of false-positive supraclavicular lymph node (LN) detected on chest computed tomography (CT), using subsequent neck ultrasonography (US) and US-guided tissue sampling. Among 172 patients with suspected supraclavicular LNs identified on CT, 87 underwent neck US or US-guided tissue sampling. Receiver operating characteristic curve and logistic regression analyses were performed to determine the diagnostic performance of US and independent predictors of false-positive LNs. Among 87 patients, 49 (56.3%) were pathologically confirmed as metastases, 26 (29.9%) were negative for malignancy, and 12 (13.8%) had pseudolesions or schwannomas. The diagnostic indices were as follows: sensitivity, 91.8%; specificity, 92.3%; PPV, 95.7%; NPV, 85.7%; and accuracy, 92.0% (AUC = 0.921; 95% CI: 0.832-0.970, p < 0.001). The false-positive group had a higher mean age than the true-positive group (mean age, 69.8 ± 9.2 vs. 63.9 ± 9.8, p = 0.003). Logistic regression analyses revealed that age ≥ 65 years was the only independent predictor of false-positive LNs (OR = 4.391; 95% CI: 1.037-18.582; p = 0.044). Subsequent US can be helpful for evaluating suspicious supraclavicular LNs detected on CT to establish appropriate management, especially in older patients.

Axillary Lymph Node Metastasis from Ovarian Carcinoma: A Systematic Review of the Literature.

Axillary lymph node metastasis is a rare stage IV ovarian carcinoma manifestation. This manuscript aims to systematically review the literature regarding axillary lymph node metastasis from ovarian carcinoma. We searched three medical internet databases (PubMed, Scopus, and Web of Science) for relevant articles published until 22 July 2023. Cases describing supraclavicular or intramammary lymph node metastases and concurrent metastasis to the breast were excluded. After applying eligibility/inclusion and exclusion criteria, twenty-one manuscripts describing twenty-five cases were included from the English literature. Data were collected and analyzed regarding demographic, clinical, laboratory, radiological, histopathological, and oncological characteristics. We analyzed the clinical and oncological characteristics of patients with axillary lymph node metastasis from ovarian carcinoma, presented either as an initial diagnosis of the disease or as a recurrent disease. The analysis we performed showed a significant difference only in the serum CA-125 level (p = 0.004) between the two groups. There was no observed difference in womens' survival.

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.

Correlation between Baseline Conventional Ultrasounds, Shear-Wave Elastography Indicators, and Neoadjuvant Therapy Efficacy in Triple-Negative Breast Cancer.

In patients with triple-negative breast cancer (TNBC)-the subtype with the poorest prognosis among breast cancers-it is crucial to assess the response to the currently widely employed neoadjuvant treatment (NAT) approaches. This study investigates the correlation between baseline conventional ultrasound (US) and shear-wave elastography (SWE) indicators and the pathological response of TNBC following NAT, with a specific focus on assessing predictive capability in the baseline state. This retrospective analysis was conducted by extracting baseline US features and SWE parameters, categorizing patients based on postoperative pathological grading. A univariate analysis was employed to determine the relationship between ultrasound indicators and pathological reactions. Additionally, we employed a receiver operating characteristic (ROC) curve analysis and multivariate logistic regression methods to evaluate the predictive potential of the baseline US indicators. This study comprised 106 TNBC patients, with 30 (28.30%) in a nonmajor histological response (NMHR) group and 76 (71.70%) in a major histological response (MHR) group. Following the univariate analysis, we found that T staging, dmax values, volumes, margin changes, skin alterations (i.e., thickening and invasion), retromammary space invasions, and supraclavicular lymph node abnormalities were significantly associated with pathological efficacy (p < 0.05). Combining clinical information with either US or SWE independently yielded baseline predictive abilities, with AUCs of 0.816 and 0.734, respectively. Notably, the combined model demonstrated an improved AUC of 0.827, with an accuracy of 76.41%, a sensitivity of 90.47%, a specificity of 55.81%, and statistical significance (p < 0.01). The baseline US and SWE indicators for TNBC exhibited a strong relationship with NAT response, offering predictive insights before treatment initiation, to a considerable extent.

Diagnostic Performance of PSMA-Based 18F-DCFPyL PET/CT in Prostate Cancer Patients After Definitive Treatment With PSA Level ≤0.2 ng/mL.

The aim of this study was to investigate the role of 18F-DCFPyL PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment and with low-level prostate-specific antigen (PSA) level of ≤0.2 ng/mL. This retrospective study was conducted in PC patients who received definitive treatments with PSA level of ≤0.2 ng/mL and underwent 18F-DCFPyL PET/CT within a 1-week interval of PSA examination, and without interval treatment change or history of other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on 18F-DCFPyL PET/CT were collected. Patients with minimal 6-month (median, 11 months; range, 6-21 months) follow-up or definitive biopsy results of the suspected PET/CT findings were included. Imagine findings were reached with consensus among experienced board-certified nuclear medicine physicians. Comprehensive follow-up and/or biopsy results were used as definitive determination of presence or absence of disease. Comparisons between groups of positive and negative 18F-DCFPyL PET/CT were done by using descriptive statistics. A total of 96 18F-DCFPyL PET/CTs from 93 patients met the inclusion criteria. The median Gleason score (GS) of positive group is 8 (range, 6-10), whereas negative group is 7 (range, 6-10). The median age of positive group is 71 (range, 50-90), whereas negative group is 69 (range, 45-88). There were 49 positive (51%) and 47 negative 18F-DCFPyL PET/CTs (49%). Detection rates at PSA level of ≤0.1 and 0.2 ng/mL were 58.7% (27/46) and 44% (22/50), respectively. The scan-based sensitivity, specificity, positive predictive value, and negative predictive value are 100%, 95%, 96%, and 100% in group with PSA level of ≤0.1 ng/mL, and 100%, 97%, 95%, and 100% in group with PSA level of 0.2 ng/mL, respectively. Sites of involvement on positive 18F-DCFPyL PET/CTs were prostate bed, pelvic lymph nodes, bone, chest and supraclavicular lymph nodes, lung, and adrenal glands. The SUVmax value on positive lesions ranged from 1.9 to 141.4; the smallest positive lymph node was 0.4 cm. High GS of 8-10, known metastatic status (M1), presence of extraprostatic extension, presence of seminal vesicle invasion, and very high-risk PC are significantly associated with positive 18F-DCFPyL PET/CT results (P < 0.05). Of all analyzed treatment regimes, upfront surgery (radical prostatectomy with or without pelvic lymph node dissection) had strong correlation with negative PET/CT results (P < 0.001). If patients received ADT only, or ADT plus chemotherapy, the PET/CT results were most likely positive (P = 0.026). For other treatment regimes, there were no statistical differences between the groups (P > 0.05). In the presence of low PSA level in PC patients after definitive treatment, 18F-DCFPyL PET/CT is most beneficial in detection of disease in patients with GS of 8 or higher at the time of diagnosis, and the ones who have history of ADT only, or ADT plus chemotherapy. There is excellent negative prediction value of 18F-DCFPyL PET/CT. However, there is no cutoff PSA level for 18F-DCFPyL PET/CT indication and no correlation between PSA level and SUVmax of positive lesions on 18F-DCFPyL PET/CT.

SAT564 Metastatic Malignant Pleural Effusion In A Patient With Remote History Of FTC

Abstract Disclosure: D.M. Lee: None. M. Gong: None. C. Czerlanis: None. A. Arif: None. R. Arceo-Mendoza: None. Introduction: Differentiated thyroid follicular epithelial-derived cancers include Papillary (PTC) and Follicular Thyroid Cancer (FTC). FTC is less common, accounting for only 5-15% of all thyroid cancers. It is more common in older patients and spreads via hematogenous route, with distant metastases in 10-15% of patients, commonly in the lungs and bone. We describe an unusual case of a patient with a remote history of FTC who presents with recurrence more than 50 years later in the form of a malignant pleural effusion. Clinical Case: A 79/M with a remote history of FTC that was diagnosed in the 1960s presents with one week of L sided pleuritic chest pain and dyspnea. CXR on admission showed opacification of the L hemidiaphragm. A chest CT confirmed the L sided pleural effusion. Thyroid US showed surgically absent thyroid and a 1.1cm solid nodule in the L surgical bed. PET/CT demonstrated hypermetabolic rim of L pleural effusion with no uptake in the neck. Thoracentesis was done which showed exudative pleural fluid concerning for malignancy. Immunohistochemical stains were positive for TTF-1 and thyroglobulin, consistent with metastatic thyroid cancer. He also underwent L supraclavicular lymph node FNA with findings suspicious for metastatic thyroid cancer with follicular features, with NO nuclear features of PTC. On further history, the patient reports having radiation therapy for acne around age 17 and was then diagnosed with FTC in his 20s. He underwent total thyroidectomy and RAI treatment. He recalls being told that he had a few weeks to live, and an “experimental treatment” was offered at the time, which we suspect was cobalt radiation. The patient unfortunately was eventually lost to endocrine follow up but denies any known recurrence prior to this admission. Upon discharge, an I-123 WBS was performed showing multiple foci in the R neck. Uptake is also noted in bilateral lung base, greater on the left. He was treated with 250 mCi I-131. He is currently doing well overall, asymptomatic, and with stable surveillance imaging. He is on levothyroxine suppression therapy with Tg level on a downward trend. Clinical Lesson/Conclusion: Involvement of pleural fluid by metastatic thyroid cancer though reported, is relatively rare, accounting for only less than 1% in all the patients with malignant pleural effusion. To our knowledge, there are no reported cases of malignant pleural effusions from metastatic FTC presenting remotely so many years after the initial diagnosis. The diagnosis of metastatic thyroid cancer in pleural fluid can be challenging and knowledge of the clinical context, even with remote history dating back 50 years ago just like in our case, and supporting immunohistochemical stains is essential for making the right diagnosis. Presentation Date: Saturday, June 17, 2023

SAT541 Pleural Effusion As First Manifestation Of Recurrent Follicular Thyroid Cancer

Abstract Disclosure: N.S. Kadakia: None. C.A. Poku: None. Pleural effusions are a rare presentation of Follicular Thyroid Cancer (FTC). We portray a case of a patient with a remote history of FTC who presented with pleural effusion 57 years later as the first sign of recurrence. A 80 year old male presented to the hospital 8/2021 with shortness of breath and was found to have a pleural effusion. He had a history of FTC diagnosed at age 23 status post total thyroidectomy, external beam radiation and radioactive iodine. He was started on thyroid hormone replacement and was subsequently lost to follow up. Chart review showed unremarkable neck ultrasounds completed in 2004 and 2006. During admission 8/2021, a malignant pleural effusion was diagnosed after the effusion tested positive for TTF-1 and thyroglobulin (Tg). He was diagnosed with recurrent metastatic thyroid cancer. A CT scan of the neck showed a small paratracheal nodule while a PET scan revealed hypermetabolic activity in the left pleura. A neck ultrasound reported a 2 cm cervical lymph node on the right with preserved fatty hilum and an ovoid 1 cm isoechoic solid nodule in the left surgical bed. There was evidence of bulky calcified lymph nodes on CT. The pleural lesion was not accessible however biopsy of a supraclavicular lymph node was consistent with metastatic follicular carcinoma. After a delay due to iodine contrast exposure, a whole body scan with radioactive iodine was completed in 1/2022 and showed multiple foci of uptake in the right neck, right thyroid, left clavicular region, and lung bases. He was treated with 250 mCi I-131 sodium iodide in 1/2022 and levothyroxine dose was increased with a target TSH of less than 0.1. His Tg level was mildly increased. Thyroglobulin antibodies (Tg ab) were positive but have continued to trend down after treatment. A follow up CT chest done 7/2022 had persistent pleural thickening but significant improvement in pleural effusion and thus thyroxine kinase inhibitors (TKI) chemotherapy has not been initiated. Malignant pleural effusion is a rare presentation of FTC metastasis with a reported median survival of 11 months (Kazushige). Pleural effusion is a poor prognostic sign in patients with FTC and distant metastases (Broome). This affirms that prompt recognition is of essence however it also raises the question of how effective current therapies are. A retrospective study evaluated 20 patients who received RAI for pulmonary metastasis from FTC, and found the efficacy rate was relatively low (40%). There is insufficient data to determine the effectiveness of RAI as treatment for metastatic FTC to the pleura. This case adds to the limited literature on recurrence of FTC with pleural effusion and highlights limitations of current management. If the response to RAI is deemed inadequate then consideration should be given to the use of TKI. Presentation Date: Saturday, June 17, 2023

SAT576 Change Is Not Always For The Best! A Transformation of Papillary Into Metastatic Anaplastic Thyroid Carcinoma

Abstract Disclosure: J. Syeda: None. R. Zafar: None. K. Rajamani: None. INTRODUCTION: Anaplastic thyroid carcinoma (ATC) can occur de-novo or from preexisting well-differentiated thyroid carcinoma (1). The presence or absence of certain driver mutations can help predict the likelihood of this transformation process. We present a case of an elderly female with an initial diagnosis of well-differentiated papillary thyroid cancer (PTC) with a transformation into metastatic anaplastic thyroid carcinoma (ATC). CASE PRESENTATION: An 81-year-old female patient was initially seen 8 years ago with a 35-year history of goiter. At the initial presentation, she felt well and did not have any symptoms. Physical examination revealed an enlarged thyroid gland with left lobe nodularity. A thyroid ultrasound showed a multinodular thyroid gland including a 2x1.7x1.2 cm solid nodule with macro calcifications in the right lobe, 2.8x2.6x2.5 cm solid nodule, and 1.6x1.3x1.6 cm heterogeneous solid nodule with calcifications and irregular margins in the left lobe. She had a fine needle aspiration of these three nodules. The right nodule was non-diagnostic and both left nodules were positive for PTC. She underwent a total thyroidectomy and central lymph node dissection. Radioactive iodine treatment with 163mCi was administered after surgery. One and a half years after surgery, her thyroglobulin levels started trending upward. This led to a further workup including a PET/CT scan, which showed a hyper metabolic 6 mm left supraclavicular lymph node. Needle biopsy of this lymph node disclosed metastatic PTC. The pathologic diagnosis following surgical resection was positive for metastatic poorly differentiated thyroid carcinoma. A subsequent PET/CT scan and a thyroid ultrasound showed an abnormal uptake of the left neck lymph node and additional metastatic nodes in the left neck respectively. A core needle biopsy of these lesions was positive for ATC. Foundation One CDx testing was positive for BRAF V600E, TP53, and TERT promoter mutations. Cellblock from the initial thyroidectomy was reevaluated by pathology and confirmed no evidence of ATC. Foundation One CDx testing of the thyroidectomy specimen was positive for BRAF V600E and TERT promoter mutations. Surveillance imaging shows mediastinal adenopathy, left pleural thickening, and bone and liver metastases. DISCUSSION: Anaplastic transformation is not uncommon (1). This case supports the evidence that TERT promoter mutations may not trigger anaplastic transformation but may predispose to the aggressive PTC phenotype prone to conversion to ATC when one of the ATC-related “second hit” genetic events occurs (2). This case suggests that the “second hit” event is a TP53 mutation. The detection of a TP53 mutation in PTC with an aggressive phenotype may help predict anaplastic transformation. REFERENCES: 1-Endocrine Pathology. 2021 Mar; 32(3):347-356. 2- Semin Cancer Biol. 2020 Apr; 61: 23-29. Presentation: Saturday, June 17, 2023

SAT554 Follicular Variant of PTCA Initially Presenting with Widespread Metastases

Abstract Disclosure: N.N. Bisquera: None. R.C. Mirasol: None. Background: Papillary thyroid carcinoma accounts for most cases of thyroid cancer. Most cases of PTC have a good prognosis and low incidence of metastases. The follicular variant is the most common variant. First described in the 1960’s, the understanding of FV-PTC began to evolve with molecular profiling demonstrating a similarity with FTC, and clinical behavior profiling showing that a subtype may behave like PTC with a propensity for lymph node metastases. We are presented with an unusual case of an infiltrative FV-PTC presenting with widespread multiple metastases on diagnosis. Clinical Case: A 64-year-old female, presented with 1-year history of a slowly enlarging mass on the left mandible, which was also associated with an enlarging anterior neck mass. She had no constitutional symptoms and had previously been in good health. On examination, there was a 7x8x3 cm hard, fixed left mandibular mass. There was also a palpable right thyroid nodule measuring 2.5x2 cm. There was no difficulty in swallowing or breathing, but she had some difficulty in eating due to trismus. There were no associated symptoms of hypo/hyperthyroidism. Investigations revealed a euthyroid status. CT scan showed a solid lobulated heterogeneously enhancing mass measuring 4.2x5.1x5.2cm on the body and angle of the left mandible. Ultrasound showed multiple thyroid nodules, the largest - a mixed cystic and solid mass measuring 2.9 x 2.7 x 2.17 cm on the right thyroid lobe, for which FNA was performed. Histopathology showed benign follicular nodules. Incision biopsy of the mandibular mass showed presence of thyroid tissue. Further imaging showed metastases to the left frontal, parietal bone, T7 vertebra, and bilateral lungs. The case was discussed in a multi-disciplinary tumor board meeting. With a pre-operative diagnosis of a primary thyroid malignancy, the patient then underwent a total thyroidectomy with segmental mandibulectomy. Post-operative histopathology showed a metastatic multifocal infiltrative follicular variant of PTC. RAI was administered post-surgery, and she was started on suppressive thyroxine therapy. Steroids were given during RAI, with no untoward events post treatment. Post-ablative whole body scanning revealed increased tracer uptake in multiple areas: left frontal and parietal bone, bilateral thyroidal beds, left supraclavicular lymph node, the sternomanubrial junction, bilateral lung lobes, right humeral head and T7 vertebra. Further doses of RAI was planned and she is currently maintained on suppressive thyroxine therapy. Conclusion: Diagnosis of FV-PTC may be a greater challenge than conventional forms because of possible false-negative results on cytology. The infiltrative subtype has greater metastatic potential and higher recurrence rates. Multidisciplinary team management and careful preparation prior to treatment with RAI is indicated in these cases. Presentation Date: Saturday, June 17, 2023

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

Comparison of Supraclavicular Surgery plus Radiotherapy vs. Radiotherapy Alone in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis: A Multicenter Retrospective Study

To evaluate and compare the outcomes of supraclavicular lymph node dissection (SLND) plus radiotherapy (RT) and RT alone for patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM). In all, 293 patients with sISLM across three centers were included. Of these, 85 (29.0%) received SLND plus RT and 208 (71.0%) received RT alone. All patients received preoperative systemic therapy followed by mastectomy or lumpectomy and axillary dissection. Supraclavicular recurrence-free survival (SCRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated by using the Kaplan-Meier method and multivariate Cox models. Multiple imputation was used for missing data. The median follow-up duration of the RT and SLND+RT groups were 53.7 and 63.5 months, respectively. For the RT and SLND+RT groups, the 5-year SCRFS rates were 91.7% vs. 85.5% (P = 0.522), LRRFS rates were 79.1% vs. 73.1% (P = 0.412), DMFS rates were 60.4 vs. 58.8% (P = 0.708), DFS rates were 57.6% vs. 49.7% (P = 0.291), and OS rates were 71.9% vs. 62.2% (P = 0.272), respectively. There was no significant effect on any outcome when comparing SLND+RT versus RT alone in the multivariate analysis. Based on four risk factors of DFS, patients were classified into three risk groups: the intermediate- and high-risk groups had significantly lower survival outcomes than the low-risk group. SLND+RT did not improve outcomes of any risk group compared with RT alone. Patients with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups.

Posterior Neck Coverage in Patients Receiving Regional Nodal Irradiation for Breast Cancer

Patterns-of-failure studies suggest the posterior neck (PN) may harbor microscopic disease in patients with locally advanced breast cancer. We compared target coverage, lung dose, and toxic effects in patients treated with either an anterior oblique field (AO) or opposed oblique fields (OO) to address the superior axillary and supraclavicular nodal (SCV) regions. We identified 119 consecutively treated patients who received regional nodal irradiation, including a "third field," to address the superior axillary and supraclavicular nodal regions with a monoisocentric technique in our institution. Coverage of the axillary clinical target volume (CTV), SCV CTV and PN CTV was determined based on the delivered treatment plan. Wilcoxon rank-sum test and Fisher's exact test were used to compare coverage of the axillary, SCV, and PN CTVs, lung dosimetry, and toxic effects (graded by the Common Terminology Criteria for Adverse Events v4.0) between patients receiving an AO or OO. There were 29 patients in the AO group and 80 in the OO group. All patients in the AO group received conventionally fractionated radiation versus 61% in the OO group. Modestly hypofractionated plans were delivered to 39% of the OO group. The body mass index and anterior-posterior separation at the matchline (measured at the center of the carotid artery) were similar in both groups. The median volume (%) of the SCV CTV receiving at least 90% of the prescription dose (V90%) was 91% (85, 99) in the AO group and 93% (91, 95) in the OO group (P = 0.2). The median V90% of the PN CTV was 30% (12, 49) in the AO group and 100% (100, 100) in the OO group (P<0.001). The median V90% in the axillary levels I, II and III CTVs were 98%, 95% and 90%, respectively, in the AO group and all 100% in the OO group (P<0.001). Maximum dose and heterogeneity in the SCV CTV were similar in both groups. Including only patients who received conventionally fractionated plans, the mean lung dose (cGy) was 1216 in the AO group and 1328 in the OO group (P = 0045). The lung V5 Gy, V10 Gy and V20 Gy were similar in both groups. Ipsilateral upper extremity lymphedema (all grade 1) was 3.4% in the AO group and 2.5% in the OO group (p>0.9). Moist desquamation in the neck was 0% in the AO group and 1.2% in the OO group (p>0.9). Pneumonitis (all grade 1) was 0% in the AO group and 1.2% in the OO group (p>0.9). Compared to a single anterior field, opposed oblique fields provide superior axillary and posterior neck coverage without increasing toxicity.

Variation in Left Anterior Descending Coronary Artery Accumulated Dose Estimates during Breast Cancer Radiotherapy

Left anterior descending (LAD) coronary artery RT dose has been associated with the risk of coronary ischemic events in patients with breast cancer treated with radiotherapy (RT). However, consensus dose constraints commonly utilize mean heart dose, which has been shown to be an inadequate surrogate for LAD dose. Given the LAD is adjacent to the steep dose gradients of the left breast/chest wall, we hypothesize that variations in patient positioning or depth of breath hold may contribute to significant deviations in daily LAD dose exposure compared to predicted. Our objective was to investigate variations in accumulated LAD dose in patients with left-sided breast cancer treated with RT. Retrospective analysis of 10 consecutive patients with left-sided breast cancer treated between 2019-2022 with volumetric modulated arc therapy (VMAT) in the supine position. RT was delivered using daily cone beam computed tomography (CBCT) image guidance with deep-inspiratory breath hold technique and an optical surface monitoring system. Daily CBCT scans were individually registered to each planning CT based on daily positional changes. The LAD was manually segmented and transformed to each CBCT. Daily fractional dose was calculated (mean, volume receiving 15 Gy [V15 Gy], V30 Gy, and max) and summed to produce an accumulated dose which was compared to the predicted dose. Significant deviations in accumulated dose were defined as at least ±15% from predicted. The RT targets included breast/chest wall only (n = 1), supraclavicular nodes (n = 8), and/or internal mammary chain (n = 5). All plans were prescribed to 50 Gy in 25 fractions. The median predicted mean heart dose was 5.1 Gy. Overall, there were no significant differences between the median predicted vs. accumulated LAD doses: mean 10.4 vs. 10.2 Gy, V15 Gy 21% vs. 25%, V30 Gy 0% vs. 1%, max 24.5 vs 25.7 Gy (all p>.05). However, there was a subset of patients (n = 5, 50%) with significant deviations in accumulated vs. predicted dose (at least ±15%). For LAD mean, n = 2 had higher accumulated vs. predicted doses (16.6 vs. 11.6 Gy; 14.6 vs. 12.8 Gy), while n = 3 had lower (21.8 vs. 26.5 Gy; 2.7 vs. 4.2 Gy; 13.9 vs. 16.5 Gy). For LAD V15 Gy, n = 3 had higher accumulated vs. predicted doses (43 vs. 35%; 51% vs. 25%; 14% vs. 9%), while n = 2 had lower (49% vs. 61%; 37% vs. 56%). For LAD V30 Gy, n = 4 had higher accumulated vs. predicted doses (12% vs. 5%; 5% vs. 0%; 4% vs. 0%; 4% vs. 2%), while n = 1 had lower (32% vs. 44%). Daily setup differences, including the extent of inspiratory breath hold, may contribute to deviations in accumulated LAD dose (more than 15% of predicted) in approximately half of patients and were more pronounced in V15 and V30 Gy metrics. The potential for significant LAD dose uncertainty in a clinically meaningful subset of patients should be recognized and warrants further analysis in an expanded cohort.

Dosimetric Evaluation of a Novel Non-Metallic Dual Port Expander for Proton Therapy

This study evaluates a novel non-metallic (plastic) dual port expander and clinically utilized single/dual port metallic expanders for intensity modulated proton therapy (IMPT) in order to quantify the dosimetric implications in clinical treatment plans. Four previously treated breast cancer patients (3 left sided, 1 right sided) with tissue expanders were retrospectively planned for IMPT utilizing a treatment planning system. Utilizing the existing CT data sets, models of three Sientra tissue expanders (dual port plastic (DPP), dual port metal (DPM) and single port metal (SPM)) were inserted into the 3D dataset and aligned using the existing patient anatomy. Each patient was planned to a total dose of 50.4 Gy in 28 fractions using 3 incident proton fields and Monte Carlo calculation algorithm. A 5 mm expansion was placed around the metallic portion of the expander to define a beam avoidance region which no proton spots traversed or were placed to minimize dosimetric error. Robust optimization (5mm setup uncertainty, 3.5% range uncertainty) was employed to a total target volume which comprised the CTV chest wall, IMN, axilla and supraclavicular nodes. The subsequent treatment plans were evaluated for target and OAR coverage. Due to the non-metallic construction of the DPP expander, the metallic structure avoidance region was significantly smaller at 4.4cc on average than either the SPM (45cc average) or DPM (63.5cc average). This allowed the IMPT plans to be significantly less modulated, delivering a more uniform dose to the implant volume (SPM 47.1Gy; DPM 45.2 Gy; DPP 50.9 Gy) and thus enabling these plans to be inherently more robust to setup uncertainties. The additional benefit of the reduced avoidance region size is that the hinge angle of the lateral proton beams can be reduced for DPP plans thus reducing dose to the heart and contralateral breast. Average mean heart dose across the four cases presented is 0.68 Gy, 1.03 Gy, and 0.93 Gy, for the DPP, DPM and SPM cases respectively, while average contralateral breast/CW dose is 0.38 Gy, 0.58 Gy and 0.63 Gy. The V20 for the ipsilateral lung was, on average, reduced for the DPP expander at 14.3% across the 4 cases, while 18.8% and 17.0% for the DPM and SPM cases respectively. The minimization of metal in the DPP expander allows for a significantly smaller beam avoidance region, in-turn enabling creation of a more homogeneous plan that can be potentially more robust while also reducing dose to surrounding OARs. Additional work is underway to expand the study to include a larger patient cohort, while also evaluating the impact of different robustness goals on OAR sparing.

Nodal Response to Neo-Adjuvant Systemic Therapy Predicts Prognosis of cN3c Breast Cancer Patients Receiving Multidisciplinary Therapy

cN3c breast cancer with ipsilateral supraclavicular (SCV) lymph nodal (SCLN) metastasis has a dismal prognosis. We investigated the survival outcomes, patterns and risks of recurrence in those patients after multidisciplinary therapy, as well as the predictors of candidates for SCV area boosting. Consecutive cN3c breast cancer patients without distant metastases from January 2009 to December 2020 in our institution were retrospectively reviewed. Based on nodal response to neoadjuvant therapy (NAT), patients were categorized into three groups: clinical complete response (cCR) not achieved in SCLN (Group A, n = 66), SCLN cCR but axillary node (ALN) did not achieve pathological complete response (pCR, Group B, n = 34), cCR in SCLN and pCR in ALN (Group C, n = 13). The median follow-up time was 32.7 months (range, 21.9-53.3months). The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 64.6% and 43.7% respectively. Multivariate analysis showed cumulative SCV dose and ypT stage, ALN response and SCV response to NAT were significantly associated with OS and RFS respectively. The 3-year for patients receiving the cumulative SCV dose of ≥60 Gy versus <60 Gy was 81.3% versus 69.0% (P = 0.042). Compared with Group A or B, Group C showed significantly improved RFS (3y-RFS: 53.8% vs 73.6% vs 100%, p = 0.003) and a numerically longer OS (3y-OS: 73.4% vs 86.7% vs 100%, p = 0.089). Meanwhile, Group C showed the lowest rate of DM as first failure (37.9 % vs 23.5% vs 0 in group A, B and C, respectively, p = 0.010). In patients of Group A, the 3-year OS rates for patients receiving the cumulative SCV dose of ≥60 Gy versus <60 Gy was 78.0% versus 57.3% (p = 0.029). Nodal response to NAT is an independent prognostic factor for survival and pattern of failure. cN3c breast cancer patients with SCLN cCR and ALN pCR after NAT are potentially curable. A cumulative SCV dose of ≥60 Gy is positively associated with improved OS, especially in patients of SCLN without achieving cCR. Our data supports the perspective of optimizing radiotherapeutic strategy based on nodal response.

Laryngo-Esophageal Dysfunction Free Survival of Chemoradiation for Cervical Esophageal Cancer

Chemoradiotherapy is often the treatment of choice for cervical esophageal cancer due to the invasiveness of surgery. However, toxicity after chemoradiotherapy often affects the quality of life related to swallowing and speech. This study evaluated laryngoesophageal dysfunction-free survival (LEDFS) in patients with cervical esophageal cancer, which has recently been used in head and neck cancer. We analyzed 59 patients with cervical esophageal cancer without distant metastases other than supraclavicular lymph node metastases who received radical chemoradiotherapy with 5-fluorouracilplus platinum between 2002 and 2018. Loco-regional control (LRC), overall survival (OS), LEDFS, metachronous esophageal cancer incidence rates, and late toxicities were evaluated. LEDFS events were defined as death, local recurrence, total or partial laryngectomy, tracheostomy for more than 2 years, and feeding tube use for more than 2 years, as recommended by the Larynx Preservation Consensus Panel. The Kaplan-Meier method was used to calculate survival rates. The generalized Wilcoxon test was used to compare the two groups. The Common Terminology Criteria for Adverse Events v5.0 was used to assess toxicities. The median age was 66 years (range, 38-83). There were 13 women and 46 men. Stage I, II, III, IVA, and IVB disease according to UICC 8th staging were 15, 9, 9, 10, and 16 patients, respectively. 22 received conventional radiotherapy and 37 received volumetric modulated arc therapy. The median total irradiation dose was 66 Gy. Platinum plus 5-fluorouracil chemotherapy was administered to all patients. The median follow-up for survivors was 87.5 months. The 5-year LRC, OS, and LEDFS rates were 54.2%, 48.9%, and 41.9%, respectively. The prognostic factors for OS were performance status (PS), hypopharyngeal extension, and clinical stage in univariate analysis and only clinical stage (hazard ratio [HR] 3.87, 95% Confidence interval [CI]: 1.52-9.87, p<0.01) in multivariate analysis; the prognostic factors for LEDFS were PS, hypopharyngeal extension and clinical stage in univariate analysis and hypopharyngeal extension (HR 2.38, 95% CI: 1.12-5.03, p = 0.02) and clinical stage (HR 4.07, 95% CI: 1.48-11.06, p<0.02) in multivariate analysis. Metachronous esophageal cancer was observed in 28.6% of patients at 5 years. As severe late toxicities, grade 3 pneumonitis, esophageal stricture, esophageal fistula, laryngeal stricture, and laryngeal edema were observed in 1 (2%), 1 (2%) and 4 (7%), 1 (2%) and 1 (2%), respectively. Grade 2 hypothyroidism was observed in 31 (53%) patients. Chemoradiation for cervical esophageal cancer showed good results. The prognostic factors for LEDFS were pharyngeal extension and clinical stage. Late esophageal and laryngeal toxicity, hypothyroidism, and metachronous esophageal cancer should be noted.