Supraclavicular Nodes Research Articles

Trends in incidence of infrequent and frequent synchronous metastases from colorectal cancer

BackgroundPopulation-based data on the incidence of frequent colorectal metastases are fairly scarce, while that on rare metastatic sites are lacking. AimsThe aim of this study was to provide epidemiological indicators of metastatic sites frequency in patients with colorectal cancer. MethodsIncidence was modelled using Poisson and Joinpoint regressions in a population-based cancer registry study including metastatic colorectal cancers diagnosed between 1991 and 2020 (N = 5,199). Tumor molecular markers were collected for the [2016–2020] period. ResultsLiver, peritoneum, lung and bone were the most frequent metastatic sites. Among frequent sites, incidence of liver and lung sites decreased in men respectively since 1999 and 2010, whereas in women incidence of liver and peritoneum sites increased steadily throughout the whole period. Each of the other sites concerned less than 3% of metastatic colorectal cancer cases and presented standardized incidence rates between 0.19 and 1.39 per 1,000,000. Among rare sites, incidence of adrenal glands, supraclavicular lymph node, mediastinum and ascites had doubled in [2016–2020] as compared to the 25 previous years. BRAFV600E variant was more frequent in presence of carcinomatosis, and absence of liver and lung metastasis while KRAS variant was more frequent in presence of lung metastasis. ConclusionThis study provides unprecedented incidence indicators for rare synchronous metastases of colorectal cancer.

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

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

Evaluating the efficacy of chemoradiotherapy combined with immunotherapy for local-regional recurrent esophageal cancer patients after esophagectomy: A retrospective analysis.

e16085 Background: Chemoradiotherapy has been the standard-of-care for esophageal cancer patients with local-regional recurrent disease after esophagectomy without prior chemoradiation. Recent studies have demonstrated that immune checkpoint inhibitors confer survival benefits to patients with esophageal cancer. However, the effectiveness of chemoradiotherapy combined with immunotherapy remains undetermined in patients experiencing local-regional recurrence. Methods: Esophageal cancer patients treated at our institution were screened retrospectively for the following inclusion criteria: histological confirmation of squamous cell carcinoma; loco-regional recurrence after surgery-based first-line treatment; received chemoradiotherapy combined with immunotherapy regimen after loco-regional recurrence. Patients with prior radiotherapy were excluded. The endpoints of the study were overall survival (OS) and progression-free survival (PFS). Loco-regional recurrence was defined as recurrences from below the hyoid to the lower margin of the first lumbar vertebra, including supraclavicular, mediastinal, abdominal lymph nodes, and the tumor bed. PFS was defined as the time from the date of postoperative recurrence until disease progression, recurrence, death, or the last follow-up day; OS was determined as the duration from postoperative recurrence to the date of death from any cause or the last follow-up date. Results: Between January 2020 and July 2023, 685 patients were screened and 61 patients were finally enrolled in this study. The median follow-up period was 14 months (2.9~45.5 months). Regarding the regions of recurrence, 31 patients experienced exclusive mediastinal recurrence, and 30 patients had recurrence beyond the mediastinum (supraclavicular lymph node [n = 21], abdominal lymph node [n = 8], both supraclavicular and abdominal lymph node [n = 1]). In these cases, 26 patients (43%) experienced recurrence after receiving chemoradiotherapy combined with immunotherapy (loco-regional failure [n = 15], distant metastasis [n = 3], and both loco-regional failure and distant metastasis [n = 8]). Fourteen (23%) patients died from disease progression. The median PFS was 18 months (95%CI, 9.6-26.4) and the median OS was not reached. The 2-year OS rate was 65%. In univariate analysis, patients with recurrence in supraclavicular/abdominal lymph nodes had a worse prognosis (P = 0.014, HR = 2.765). Conclusions: Chemoradiotherapy combined with immunotherapy showed a favorable efficacy in radiotherapy-free esophageal cancer patients experiencing loco-regional recurrence post-surgery. Additionally, the regions of recurrence may influence patient outcomes.

Prognosis of locoregional recurrence after early breast cancer with immediate breast reconstruction.

e12595 Background: Several studies have shown no difference in the prognosis of breast cancer patients who underwent total mastectomy (MT) with or without immediate breast reconstruction (IBR), which is now a standard surgical technique in the treatment of breast cancer. While some studies have reported a poor prognosis for locoregional recurrence (LRR) following breast cancer surgery, the prognosis of LRR without simultaneous distant metastasis after IBR is not known. We conducted a multi-facility retrospective observational study to investigate the prognosis of breast cancer patients with LRR after IBR. Methods: Of the 4,726 primary breast cancer patients for whom IBR was performed at 12 Japanese medical facilities between January 1, 2008, and December 31, 2016, MT or skin-sparing mastectomy (SSM) was performed in 3,295 patients. LRR was observed in 87 of these patients, 17 of whom had distant metastasis (n=13) or metastasis to the supraclavicular or internal mammary lymph nodes (n=4) before LRR was excluded. The measured outcomes were IBR-LRR-related prognostic factors, five-year distant metastasis-free survival (DMFS), and five-year overall survival (OS). The statistical analyses employed Kaplan–Meier curves and a Cox proportional hazards model. Results: The median observation period was 39.3 months and the median age at which IBR was performed was 44 years. There were 61 cases (87.1%) of invasive cancer. Sixty-one cases (87.1%) were ER-positive, 54 (77.1%) were PR-positive, and 13 (19.7%) were HER2-positive. Fifteen cases (21.4%) had pathological lymph node metastasis (pN), 60 cases (85.7%) underwent implant reconstruction, 33 cases (47.1%) had a disease-free interval ≤ 36 months, 9 cases (12.9%) had regional lymph node recurrence (RR), and 65 cases (92.9%) underwent surgical resection to treat LRR. The five-year DMFS after LRR was 92.4%, and the five-year OS was 91.2%. The relationship between DMFS and clinical pathology factors was analyzed using a Cox proportional hazards model. Univariate analysis revealed significant differences for pN (HR 10.634, 95% CI 1.102–102.616, P=0.041) and RR (HR 9.960, 95% CI 1.400–70.862, P=0.022), and multivariate analysis indicated that RR was the only independent prognostic factor for DMFS (HR 7.834, 95% CI 1.085–56.587, P=0.041) (Table 1). Univariate analysis revealed significant differences for post-mastectomy radiation therapy (PMRT) (HR 130.676, 95% CI 1.552–412.278, P=0.023) and RR (HR 8.181, 95% CI 1.106–60.503, P=0.043), and multivariate analysis indicated that both PMRT (HR 61.281, 95% CI 2.540–1478.426, P=0.010) and RR (HR 15.687, 95% CI 1.354–181.772, P=0.028) were independent prognostic factors for OS. Conclusions: This is the first study to report the prognosis of breast cancer patients with LRR after IBR. Although these patients have a favorable prognosis overall, our results indicate that RR may be a significant factor for poor prognosis.

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

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

The role of immunotherapy in the treatment of lip squamous cell carcinoma: A series of six cases and a review of the current literature

BackgroundSquamous cell carcinoma (SCC) of the lip is a distinct subtype of oral cavity SCC, accounting for about 10–20 % of all oral cavity cancers. According to National Comprehensive Cancer Network (NCCN) guidelines, treatment consists of surgical resection with adjuvant radiotherapy or chemoradiotherapy as indicated. The role of immunotherapy as a treatment modality remains unclear. MethodsWe identified six patients with SCC of the lip who had locally advanced or recurrent disease and treated with PD-1 inhibitors, either as monotherapy or as part of a chemo-immuno regimen. Three patients were diagnosed with locoregional recurrences after conventional treatment failure, one of whom concurrently diagnosed with distant metastases. Two cases involved treatment with immunotherapy as an alternative to surgery or radiotherapy. Clinical and radiological responses were assessed, and side effects were recorded. ResultsAll patients exhibited complete clinical response, five showed complete radiological responses per PET-CT. One patient was yet to be assessed radiologically. Another had a PET-avid supraclavicular node negative for malignancy. The median follow-up time since treatment initiation was 11.49 months (IQR 7.77 - 29.03). Adverse effects included severe myositis (n = 1), arthralgia (n = 1), psoriasis (n = 1), esophagitis (n = 1), mild hepatitis (n = 1) and pruritus (n = 2). Management included corticosteroids (topical or systemic) and/or 2nd generation antihistamines and treatment cessation as indicated. ConclusionImmunotherapy shows promise for lip SCC after conventional treatment failure or as an alternative to surgery or radiotherapy in unsuitable candidates, suggesting a tumor biology resembling cutaneous rather than oral cavity SCC. Patients should be closely monitored for potential side effects.

Association of Radiation-Induced Acute Esophagitis With Dosimetric Parameters of Oesophagus in Breast Carcinoma Patients Receiving Supraclavicular Nodal Irradiation.

We conducted this investigation to ascertain the dosimetric properties such as the mean and maximum radiation dosage during radiotherapy as well as the extent of radiation exposure to the esophagus. These factors can potentially impact the development of esophagitis in breast cancer patients undergoing supraclavicular radiation. From January to June 2023, an observational study was conducted at Bangabandhu Sheikh Mujib Medical University in Bangladesh. The patients received radiation therapy (40.05 Gy in 15 parts) to the chest wall and supraclavicular node for three weeks. We were able to guess the following from the dose volume histogram (DVH) data: the length of the esophagus in the treatment area (i.e., the size of the esophagus that was visible on the planning CT scan), the maximum dose (Dmax), the mean dose (Dmean), and the volume of the 10Gy (V10Gy) and 20Gy (V20Gy) doses that were given to the esophagus. During radiotherapy, patients were checked on once a week, and the radiotherapy oncology group was used to evaluate and grade esophagitis Results: Patients with left-sided breast cancer showed a higher Dmean, Dmax, and length of the esophagus compared to those with right-sided breast cancer. Specifically, the Dmean was 6.7 (±2.1) Gy, the Dmax was 39.2 (±1.5) Gy, and the length of the esophagus was 6.1 (±1.2) Gy. Patients with left breast cancer had elevated V10Gy and V20Gy values for the esophagus, but the difference was not statistically significant. The incidence of V10Gy for right-sided breast cancer and left-sided breast cancer was 4.2% (±2.6%) and 19.8% (±9.2%), respectively. The V20Gy was 2.4% (±0.9%) for right-sided breast cancer and 13.09% (±5.0%) for left-sided breast cancer Conclusion: In conclusion, there is a strong association between the mean oesophageal dose and radiation to the left supraclavicular region following surgery in women with breast cancer and acute esophagitis. We can reduce esophageal toxicity by prescribing dose restrictions and performing precise delineation of the esophagus.

Feasibility and Toxicity of Hypofractionated Radiation Therapy in Patients Undergoing Post Mastectomy Radiation Therapy

Introduction: Post mastectomy radiation (PMRT) plays major role in breast cancer treatment. Hypofractionated radiation is a relatively newer modality. Hypofractionation is more commonly used after breast conservation surgery. Landmark trials that studied hypofractionation had fewer PMRT subjects. Here we report our study on feasibility and toxicity profile of hypofractionated PMRT. Aim: To describe the clinical and toxicity profile of patients undergoing hypofractionated 3D conformal radiation therapy in breast cancer patients. Materials & Methods: This study included patients who are eligible for post mastectomy radiation therapy above 18 years planned for adjuvant PMRT (40.05Gy in 15 fractions delivered over 3 weeks in 3D conformal radiation) to the chest wall and supraclavicular nodes between April 2021 to October 2022., active lung infection, patient preference for conventional fractionation. Dosimetric parameters to target & organs at risk were analyzed. Toxicities including hematologic, dermatitis, pharyngitis & other were monitored. Results: Of 71 patients, 70 patients were female and 1 is male. Majority (46%) of patients belonged to 46-55 years age group. Age ranged from 34 to 85 years. Mean age is 52 years. Clinical Stage IIIA was the most common stage with 29.5% patients followed by Stage IIB with 25.3% patients. Majority received adjuvant chemotherapy (52%). Mean treatment time is 21 days. All patients completed treatment without any major complications. Follow up ranged from 17 months to 27 months. Out of 71 patients, 1 patient expired on follow up after 4 months of radiation therapy due to non cancer related cause (Chronic pancreatitis). On follow up, 3 patients had distant metastasis alone (lung, bone metastasis, brain metastases) and 1 patient had both local disease and distant metastasis. 3 patients who progressed had stage IIIC disease & 1 had stage IIIB disease. The V90 to the Planned Target volume (PTV) ranged from 90.4% to 99% to right sided disease, 90.3% to 96.5% to left sided disease. Heart V17Gy ranged from 1.27% to 12.5% & heart V35Gy was 0.16% to 7.2%. Dermatitis was the most common adverse effect in this study. 31 patients (43.6%) developed fatigue during treatment. They continued their daily activities without any limitations. 35 patients (49.2%) had throat pain, of which 2 patients had it in 1st week, 21 patients had it in 2nd week and 12 patients had it in 3rd week. They were treated with non opioid analgesics. Shoulder pain was observed in 10 patients (14%) during treatment. Blood parameters were monitored weekly during treatment. No changes were observed. Conclusion: Hypofractionated post mastectomy radiation therapy is well tolerated in our study group. None of them developed any major acute reactions during and post treatment in the follow up period. Patients completed their treatment without any breaks during treatment. Respiratory motion management especially left sided disease patients should be used for achieving dose constraints.

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

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

“A Concealed Malignancy” A Case Series on Primary Fallopian Tube Carcinoma

Background: As rare as it is, primary fallopian tube carcinoma presents with a varied range of nonspecific signs and symptoms making its preoperative diagnosis a clinical challenge. It is often missed and is usually recognized later by histopathology. This paper aims to present four cases of fallopian tube cancer managed in our institution in a 5-year period with varied presentation and to discuss updates in diagnosis, management and prognosis in the light of recent literature. Methods and Results: All of the four cases were of different age group, presented differently and were diagnosed preoperatively to be of another etiology. The first case, 44 year old, initially presented with recurrent vaginal discharge. The patient then presented with supraclavicular nodes to be of metastatic origin. The second case, 58 year old, presented with vaginal spotting and on imaging, a pelvic mass that may represent ovarian new growth. The third and fourth case, 71 and 66 year old respectively, presented with a history of gradually enlarging abdominal mass with an imaging showing an adnexal mass. Intraoperatively, the first and third case revealed a fallopian tube that was thinned out and dilated to a granular and friable tissue. The second case had a right fallopian tube that cannot be grossly identified but an adnexal mass was noted. The fourth case showed a left fallopian tube that was converted to a tan irregular mass. Histopathology revelaed all of these cases as high grade fallopian tube serous carcinoma. Conclusion: To raise suspicion in the diagnosis of this rare carcinoma preoperatively should be given more importance so that a prompt investigation would be made and catching this disease in an early stage would be achieved. This paper showcased the varied presentation of this disease so as to avoid preoperative misdiagnosis and have a better head start on proper management.

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

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

Estimated Doses to the Heart, Lungs and Oesophagus and Risks From Typical UK Radiotherapy for Early Breast Cancer During 2015–2023

PurposeBreast cancer radiotherapy can increase the risks of heart disease, lung cancer and oesophageal cancer. At present, the best dosimetric predictors of these risks are mean doses to the whole heart, lungs and oesophagus, respectively. We aimed to estimate typical doses to these organs and resulting risks from UK breast cancer radiotherapy. MethodsA systematic review and meta-analysis was conducted of planned or delivered mean doses to the whole heart, lungs or oesophagus from UK breast cancer radiotherapy in studies published during 2015–2023. Average mean doses were summarised for combinations of laterality and clinical targets. Heart disease and lung cancer mortality risks were then estimated using established models. ResultsFor whole heart, thirteen studies reported 2893 doses. Average mean doses were higher in left than in right-sided radiotherapy and increased with extent of clinical targets. For left-sided radiotherapy, average mean heart doses were: 2.0 Gy (range 1.2–8.0 Gy) breast/chest wall, 2.7 Gy (range 0.6–5.6 Gy) breast/chest wall with either axilla or supraclavicular nodes and 2.9 Gy (range 1.3–4.7 Gy) breast/chest wall with nodes including internal mammary. For right-sided radiotherapy, average mean heart doses were: 1.0 Gy (range 0.3–1.0 Gy) breast/chest wall and 1.2 Gy (range 1.0–1.4 Gy) breast/chest wall with either axilla or supraclavicular nodes. There were no whole heart dose estimates from right internal mammary radiotherapy. For whole lung, six studies reported 2230 doses. Average mean lung doses increased with extent of targets irradiated: 2.6 Gy (range 1.4–3.0 Gy) breast/chest wall, 3.0 Gy (range 0.9–5.1 Gy) breast/chest wall with either axilla or supraclavicular nodes and 7.1 Gy (range 6.7–10.0 Gy) breast/chest wall with nodes including internal mammary. For whole oesophagus, two studies reported 76 doses. Average mean oesophagus doses increased with extent of targets irradiated: 1.4 Gy (range 1.0–2.0 Gy) breast/chest wall with either axilla or supraclavicular nodes and 5.8 Gy (range 1.9–10.0 Gy) breast/chest wall with nodes including internal mammary. ConclusionsThe typical doses to these organs may be combined with dose-response relationships to estimate radiation risks. Estimated 30-year absolute lung cancer mortality risks from modern UK breast cancer radiotherapy for patients irradiated when aged 50 years were 2–6% for long-term continuing smokers, and <1% for non-smokers. Estimated 30-year mortality risks for heart disease were <1%.

Abstract PO5-06-03: Impact of curative-intent treatment on survival for metastatic breast cancer limited to distant lymph nodes

Abstract BACKGROUND: Metastatic breast cancer limited to distant lymph nodes is classified as stage IV but potentially represents an anatomically distinct entity amenable to curative treatment. Its optimal management is unclear, with existing studies limited by small sample sizes and short follow-up durations. We sought to investigate the impact of curative-intent treatment on breast cancer-specific survival (BCSS) and overall survival (OS) for patients with this diagnosis. METHODS: Three cohorts of patients diagnosed with breast cancer from 2010 to 2019 were identified from the Surveillance, Epidemiology, and End Results 17 registries database. The curative cohort consisted of patients with metastatic breast cancer involving only distant lymph nodes who received a combination of chemotherapy, surgery to the primary site, and radiotherapy (curative-intent treatment). The palliative cohort included patients who underwent chemotherapy but not curative-intent treatment. The N3c cohort was comprised of patients with ipsilateral supraclavicular lymph node metastases but no distant metastases who received curative-intent treatment. Weighting based on covariate balancing propensity scores was performed to balance age, sex, race, median household income, year of diagnosis, T stage, histology, pathological grade, and ER/PR/HER2 status between the cohorts. Weight-adjusted multivariable Cox regression models with the same covariates were then used to compare the BCSS and OS of the three cohorts. RESULTS: A total of 2,089 patients with a median follow-up of 37 months were eligible for analysis, of whom 577 (27.6%) were in the curative cohort, 905 (43.3%) were in the palliative cohort, and 607 (29.1%) were in the N3c cohort. After propensity score weighting, the maximal standardized mean difference for all covariates was less than 0.1. Five-year BCSS for patients in the weight-adjusted curative, palliative, and N3c cohorts were 63.0% (95% CI 58.1-68.3), 46.7% (42.4-51.4), and 66.4% (61.4-71.8), respectively; and five-year OS were 57.9% (53.0-63.2), 41.2% (37.2-45.7), and 62.2% (57.3-67.6), respectively. Compared to the palliative cohort, the curative cohort exhibited better BCSS (HR 0.47, 95% CI 0.38-0.57; P&amp;lt; 0.001) and OS (HR 0.48, 95% CI 0.40-0.58; P&amp;lt; 0.001). In contrast, the N3c cohort had similar BCSS (HR 0.93, 95% CI 0.73-1.17; P=0.53) and OS (HR 0.96, 95% CI 0.77-1.19; P=0.68) to the curative cohort. CONCLUSIONS: Patients treated curatively for metastatic breast cancer limited to distant lymph nodes had higher BCSS and OS than those receiving palliative chemotherapy and similar BCSS and OS to patients receiving curative-intent treatment for ipsilateral supraclavicular lymph node metastases. These results support the use of aggressive multimodal therapy for select stage IV breast cancer patients with only distant nodal metastases and, if confirmed, suggest that a substantial portion of such patients may be undertreated. Citation Format: Yang Xu. Impact of curative-intent treatment on survival for metastatic breast cancer limited to distant lymph nodes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-03.

Abstract PO5-06-14: Genomic Landscape and Clinical Outcomes of Triple-Negative Invasive Lobular Carcinoma

Abstract Background: Triple-negative (TN) invasive lobular carcinoma (ILC) of the breast is a rare entity, comprising roughly 2% of primary ILC. Clinicopathologic studies have shown that TN ILC is associated with more pleomorphism, higher nuclear grade, older patient age, and worse disease-related outcomes compared to estrogen receptor-positive (ER+) ILC. Intrinsic subtyping indicates that TN ILC less frequently expresses basal markers than TN invasive ductal carcinoma (IDC). This prompted investigation of the genomic landscape and clinical management of TN ILC to provide insight into potential therapeutic approaches. Methods: Twenty patients with TN ILC were included in this study. Three patients were treated at a single academic center and underwent comprehensive genomic profiling (CGP) of breast or metastatic tissue; clinicopathologic details were obtained from their electronic health records. Seventeen patients with TN ILC who underwent CGP of breast or metastatic biopsies were included from the Foundation Medicine, Inc. database. PD-L1 testing for all patients was determined by immunohistochemistry (IHC) using the VENTANA SP142 or Dako 22C3 commercial assays. HER2 expression was determined by IHC. Negative HER2 expression was defined as an IHC score of 0, or IHC 1+ or 2+ with non-amplified fluorescence in situ hybridization (FISH). Results: In the Foundation Medicine database of patients with TN ILC, the most frequent genomic alterations were in CDH1 (15/17 patients [88.2%]), TP53 (10/17 patients [58.8%]), and PIK3CA (10/17 patients [58.8%]). Short variant mutations in ERBB2 were found in 3/17 patients (17.6%). Fourteen patients were HER2-low (HER2 IHC 1+ or 2+ with non-amplified FISH). No cases were MSI high or expressed PD-L1 (8 of 17 cases underwent PD-L1 assessment by SP142). Median tumor mutational burden (TMB) was 5 muts/Mb. Among the three patients with TN ILC treated at a single center, the most common somatic mutations were in CDH1 and TP53, and no cases were MSI high or expressed PD-L1 (by SP142 or 22C3). All three patients had pleomorphic ILC, histologic grade 2 or 3, and HER2 IHC 0. One patient with mpT1cN1a(sn) ER+/HER2- ILC of the right breast in 2011 received adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), breast/axillary radiation, and ten years of adjuvant endocrine therapy. She was diagnosed with TN ILC of the left supraclavicular nodes in 2022; she did not exhibit a response to docetaxel and carboplatin with pembrolizumab, and she subsequently received palliative radiation followed by capecitabine. Another patient with locally advanced TN ILC progressed on the KEYNOTE-522 regimen, immediately developed metastases, and is currently receiving palliative sacituzumab govitecan. The third patient with cT3N1 TN ILC progressed on neoadjuvant therapy (through the I-SPY 2 trial) with oral paclitaxel, encequidar, and dostarlimab, followed by dostarlimab with dose-dense doxorubicin and cyclophosphamide. Her surgical pathology demonstrated ypT3N3a disease with 10 × 7 cm of tumor, and she developed skin metastases on the chest wall within weeks post-operatively. She received comprehensive chest wall and nodal radiation and is currently receiving palliative capecitabine with neratinib given a high variant allele frequency driver somatic ERBB2 mutation. Conclusions: The most common somatic mutations among TN ILC patients included in this study were in CDH1, TP53, and PIK3CA. Currently the management of TN ILC is extrapolated from that of TN IDC, however our patients did not respond to chemoimmunotherapy. The presence of HER2-low status or somatic ERBB2 mutations may provide opportunities for treatment with an anti-HER2 antibody-drug conjugate or tyrosine kinase inhibitor. Studies with larger sample sizes of TN ILC are needed for molecular profiling and assessment of outcomes with specific therapeutic approaches. Citation Format: Hemali Batra-Sharma, Smruthy Sivakumar, Prashanth Ashok Kumar, Ethan Sokol, Rebecca Shatsky, Jeffrey Ross. Genomic Landscape and Clinical Outcomes of Triple-Negative Invasive Lobular Carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-14.

Survival After Contralateral Axillary Metastasis in Breast Cancer

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

Synchronous supraclavicular vascularized lymph node transfer and liposuction for gynecological cancer-related lower extremity lymphedema: A clinical comparative analysis of three different procedures

ObjectiveGynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular vascularized lymph node transfer (SC-VLNT) is a favored approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction. MethodsA cohort of 35 patients with GC-LEL was examined, comprising 13 patients who underwent single lymph nodes flap with a skin paddle (SLNF+P), 12 who received single lymph nodes flap without a skin paddle (SLNF), and 10 who accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and postoperative variables. ResultsThe median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patients noted subjective improvements in Lymphedema Quality of Life scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12-36 months), with no reported severe postoperative complications. ConclusionsFor advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.

Evaluation of Peripheral Lymphadenopathies in Children in a Single Center: Predictive Factors for Malignancy.

Lymphadenopathy (LAP) is a common finding in pediatric patients. It was aimed to determine predictive factors in distinguishing cases with malignant or benign lymphadenopathy in this study. Between January 2022 and January 2023, 101 patients (1-16 years old) with lymphadenopathy were retrospectively examined. LAP was localized in 80.2% (n=81) cases and generalized in 19.8% (n=20) cases. In 60 cases (59.4%), lymph node sizes were found to be greater than 20×20 mm in width and length. The most common infectious causative agent was Epstein Barr Virus (EBV). Seven (6.9%) patients underwent biopsy and all were diagnosed with malignancy. When the benign and malignant groups were compared, age, lymph node length, and width on physical examination, anteroposterior and longitudinal diameter of the lymph node on ultrasonography (USG) were statistically significantly higher in the malignant group (p<0.05). The presence of supraclavicular lymphadenopathy was found to be an important factor in differentiating the malignant group (p<0.003). The most important factors in distinguishing the groups are respectively were the anteroposterior diameter of the lymph node on ultrasonography and the presence supraclavicular lymph node in multivariate logistic regression analysis. It is not always easy to distinguish benign and malignant etiologies in patients with lymphadenopathy. A detailed history, a careful physical examination, laboratory studies, and excisional biopsy are guiding.

E033 Beyond the surface: artful imitation of Hodgkin’s lymphoma as axial spondyloarthritis

Abstract Background/Aims Rheumatic conditions may be associated with different neoplastic-diseases. Sacroiliitis is not defined as a paraneoplastic syndrome in the literature and considered as the direct involvement of the sacral/iliac bones or sacroiliac joints. There are only few reported cases of back pain and sacroiliac bones/joint involvement as an initial presentation of Hodgkin’s lymphoma. Methods An 18 year boy presented with low back pain of 18 months duration. He had significant morning stiffness and reported good response with non-steroidal anti-inflammatory drugs. He also complained of intermittent fever, insignificant weight loss and occasional dry cough. He denied peripheral joint pain, skin lesions, urethritis, conjunctivitis, uveitis and gastrointestinal disease. The family history was negative for spondyloarthritis (SpA) and neoplastic diseases. He was given empirical anti-tubercular drugs for 6 months with no significant improvement. He was evaluated by physician and rheumatologist elsewhere and treated as SpA in view of inflammatory low back pain, very high inflammatory markers and sacroiliac bones/joint involvement on MRI. The patient tested negative for HLA-B27 (PCR). He was initially started on sulfasalazine, however there was no induction of remission and later switched to tofacitinib since last 4 months. General examination was unremarkable. Bilateral sacroiliac compression and FABER tests were the only positive findings on systemic examination. Results There was leukocytosis (14,100/mm3) with predominant polymorphs, hemoglobin was 9.8g/dl, thrombocytosis (5.4 lakhs/mm3), serum CRP was markedly raised (123mg/L) and ESR was 57mm/hr. His workup for infectious diseases and rheumatic diseases were unremarkable. Repeat MRI according to SpA protocol showed altered marrow signal intensity in lumbar and sacral vertebral bodies and enhancing lytic lesion in right iliac bone till sacroiliac joint. PET-CT revealed multifocal FDG avid mixed lytic sclerotic lesions disseminated in the axial as well as appendicular skeleton with FDG avid sub-centimetric bilateral neck, supraclavicular, axillary, mediastinal and bilateral external/internal iliac and inguinal lymph nodes. Excision biopsy of right supra-clavicular node showed classical Hodgkin lymphoma (CD15 and CD30+ve). He was referred to the haematology clinic for further management. Bone marrow examination was suggestive of tumour infiltration. He received chemotherapy according to the protocol. He is under haematologist care and on a regular follow up with significant improvement in symptoms along with normal inflammatory markers. Conclusion There may be involvement of sacral/ iliac bones and sacroiliac joints by various malignancies including Hodgkin’s lymphoma. Morning stiffness, good response to NSAIDs and MRI findings may delay the diagnosis of primary malignancy, however we should keep a differential of lymphoproliferative disorders as in the aforementioned case and perform other diagnostic modalities. When the expected clinical response is not achieved, the physician must think of a malignancy in cases with persistently high inflammatory markers and marked constitutional symptoms. Disclosure P. Khatri: None. J. Yadavalli: None. K. Shivam: None. R. Gupta: None.

Selpercatinib for treating recurrent mixed medullary and follicular cell-derived thyroid carcinoma: a case report

BackgroundMixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell–derived tumour cell populations within the same lesion. Due to its rarity, its etiology and clinical course remain unclear, and treatment for advanced or recurrent cases has not been established.Case presentationWe report a case of MMFCC treated with selpercatinib. The patient was a 69-year-old male presenting with tumors in the right thyroid lobe and in the upper mediastinum. Fine-needle aspiration (FNA) cytology of the right thyroid lobe tumor revealed a medullary carcinoma; germline RET mutations were not detected. After resection of the right thyroid lobe with central node dissection, rapid intraoperative diagnosis of the mediastinal mass confirmed malignancy, leading to total thyroidectomy with excision of the upper mediastinal tumor. Histologically, the tumor in the right thyroid lobe and the pretracheal lymph node revealed a mixture of medullary and follicular carcinoma components, diagnosed as MMFCC. The mediastinal lymph node exhibited only medullary carcinoma components. At 11 months postoperatively, computed tomography scans showed enlargement of the right supraclavicular and upper mediastinal lymph nodes. FNA cytology of the right supraclavicular lymph node suggested the recurrence of medullary thyroid carcinoma. The gene panel testing (The Oncomine Dx Target Test Multi-CDx system®, Thermo Fisher SCIENTIFIC) of metastatic lymph node revealed RET somatic mutation (M918T). Treatment with selpercatinib was initiated, and both the cervical and mediastinal lymph nodes showed a reduction in size.ConclusionsWe report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.

A novel use of endobronchial ultrasound bronchoscope to biopsy supraclavicular lymph node

Background: Accurate staging for patients with lung cancer is essential for management and prognostication. Percutaneous ultrasound-guided fine needle aspiration (US FNA) of supraclavicular lymph nodes is not always performed clinically for variety of reasons. Our study explores the utility of supraclavicular lymph node biopsy using the endobronchial ultrasound (EBUS) bronchoscope at the time of a mediastinal staging procedure as a possible alternative to US FNA. Methods: This study included 22 patients who underwent supraclavicular lymph node biopsy using the EBUS bronchoscope during lung cancer staging procedure from 2019 to 2021 at the University of Pennsylvania. Feasibility and safety of the procedure were reported. Descriptive statistics were performed for baseline demographics, imaging features, pathology results, tumor cellularity and adequacy for oncological testing. Results: The procedures were safely performed in all patients with no safety events reported. All patients were diagnosed with malignancy and EBUS-guided supraclavicular lymph node FNA showed definitive diagnosis in 19. Of the 16 patients with the final diagnosis of non-small cell lung cancer (NSCLC), 14 had tumor seen in supraclavicular lymph node sampling and 9 were upgraded to Stage IIIB disease from lower mediastinal lymph node staging. Eleven supraclavicular lymph node samples had tumor cellularity &gt;10%. Eight samples were sent for next generation sequencing (NGS). Three of them were the only source for NGS. Conclusions: Supraclavicular lymph node biopsy using the EBUS bronchoscope is a feasible and safe procedure to perform during lung cancer staging. Sampling has significant clinical value for accurate staging and oncologic testing.