Regional Lymph Research Articles

Impact of Retroperitoneal Lymphadenopathy (RPLN) on the Outcomes of Locally Advanced Gall Bladder Cancer (GBC) Following Chemotherapy (CT) or Chemotherapy Followed by Consolidation Chemoradiotherapy (CTRT).

Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT. Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250mg/m2 to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20. Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9months (95% CI 7.6-10.3months) vs 10months (95% CI 8-9.8months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7months vs 8months, while in those who received CT followed by CTRT, the median OS was 14months vs 13months (p = 0.65) in non-RPLN group vs RPLN group, respectively. Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

Investigation of the distribution of inguinal lymph nodes and delineation of the inguinal clinical target volume using 18F-FDG PET/CT

ObjectiveRadiotherapy is a crucial treatment modality for pelvic cancers, but uncertainties persist in defining the clinical target volume (CTV) for the inguinal lymphatic drainage region. Suboptimal CTV delineation may compromise treatment efficacy and result in subpar disease control. This study aimed to investigate and map the distribution of lymph node metastases (LNM) in the groin area to facilitate an improved and detailed CTV definition using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).MethodsInguinal LNM in patients with biopsy-proven pelvic malignancies were identified using 18F-FDG PET/CT scan. The longitudinally nearest axial plane was determined based on six typical bony landmarks, and the axial direction relative to the femoral artery of LNM was recorded. The distances from the LNM to the nearest edge of the femoral artery were measured on the axial plane. An optimal margin to cover 95% of LNM was estimated to develop contouring recommendations.ResultsIn this study, 500 positive LNM were identified by 18F-FDG PET/CT among 185 patients with primary pelvic malignancies. Relative to the femoral artery, lymph nodes were distributed laterally (10:00–11:00, n = 35), anteriorly (12:00–1:00, n = 213), and medially (2:00–4: 00, n = 252). For CTV delineation, the recommended distances from the femoral artery on the SFH were lateral 19 mm, anterior 19 mm, and medial 25 mm; on the SGT were lateral 26 mm, anterior 20 mm, and medial 25 mm; on the SPS were lateral 28 mm, anterior 29 mm, and medial 26 mm; on the IPS were anterior 29 mm and medial 28 mm; on the IIT were anterior 27 mm and medial 27 mm; on the ILT were anterior 25 mm and medial 23 mm. Use interpolation to contour the area between six axial slices, including any radiographically suspicious LNM.ConclusionsUsing 18F-FDG PET/CT, we investigated the distribution pattern of inguinal LNM and propose a more comprehensive guideline for inguinal CTV delineation.

Acute radiation morbidities and dosimetric evaluation of DARS structures: Results from the phase III randomized SWOAR trial.

TPS149 Background: The SWOAR is a phase III trial (ClinicalTrials.gov ID NCT05187091) evaluating sparing of dysphagia/aspiration related structures (DARS) & submandibular gland by IMRT. Methods: Patients with T1-4, N0-3, M0 of oropharynx, larynx and hypopharynx treated with radical RT were randomized to arm A (standard IMRT) or arm B (DARS IMRT) in 1:1 manner. Treatment allocation was done based on T stage, concurrent chemotherapy use (weekly 40mg/m2) & subsite. A10-point improvement in MD Anderson Dysphagia Inventory (MDADI) composite score (primary end point of study) at 6 months post RT with SD of 17, power as 90% and two-sided alpha of 5% estimated sample size. SIB IMRT delivered dose of 66Gy (gross disease+0.5cm), 54Gy (gross disease+1cms+regional lymphatics) in 30 fractions. Acute radiation morbidities were scored by RTOG scoring criteria. Aspiration prevention assessment was done by PAS measured by FEES. Results: A total of 166 patients till date have been enrolled, 81 in Arm A & 85 in Arm B. Median age was 58 years, 73.4% had oropharyngeal primary, 89% had stage III-IV & received concurrent chemotherapy. Median composite MDADI scores pre-RT in Arm A was 70.5 (IQR 56.8-75.8) & 69.5 (56.8-75.8) in arm B. Post-RT median score dropped to 54.2 (48.8-60) in arm A & 54.8 (51.6-65.3) in arm B. Reduction in MDADI score pre & post RT in arm A was median 11.1 (0-21) & arm B was 7.9 (0-20) (p=0.28). Pre RT-PAS score was similar in both arms 1 (IOR 1-2), post-RT PAS in arm A was 1 (1-2) & arm B was 1 (1-1). Median of mean dose to SCM was 56.2Gy (46.8Gy-61.2Gy) vs 48.9Gy (36Gy-57.6Gy) p<0.003, MCM 58.5Gy (52.7Gy-63.1Gy) vs 56.2Gy (47.8-63.6) p=0.11, ICM 48.5Gy (46.8Gy-57.7Gy) vs 37.8Gy (26.5-62.4) p<0.001, base of tongue 60.5Gy (53.9Gy-64.3Gy) vs 53.9Gy (40.2Gy-62.4Gy) p=0.001,supraglottic larynx 57.7Gy (49.2Gy-64.4Gy) vs 60.5Gy (46.7-64.6) p=0.63, larynx 46.0Gy(42.4Gy-53.7Gy) vs 28.3Gy (21.5Gy-49Gy) p<0.001, cricopharyngeus 46.0Gy(43.6Gy-49.9Gy) vs 32.6Gy (27.3Gy-47Gy) p<0.001, esophageal inlet 44.6Gy (41.3Gy-47.9Gy) vs 27.2Gy (22.8Gy-39.1Gy) p<0.001, contralateral submandibular gland 52.8Gy (48.5Gy-57.2Gy) vs 40.4Gy (37.3-49.6) p<0.001, all arm A vs arm B respectively. Acute grade 3 occurred in 68.4% in arm A & 54.4% arm B, p=0.07. Acute grade 3 mucositis developed in 34.2% in arm A vs 16.7% arm B, p=0.009. Conclusions: Swallowing-sparing IMRT significantly reduced dose to contralateral submandibular gland & all the DARS structures (except middle constrictor muscle & supra glottic larynx). Dosimetric advantage gained by delivery of Swallowing-sparing IMRT resulted in significant reduction in development of acute grade III mucositis & showed a trend towards reduction in all acute grade III toxicities. Clinical trial information: NCT05187091 .

Risk factors, impact and treatment of postoperative lymphatic leakage in children with abdominal neuroblastoma operated on by laparotomy

BackgroundLymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures.MethodsA retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed.ResultsThe incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44–48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day.ConclusionsLymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day.Level of evidenceLevel III, Treatment study (Retrospective comparative study).

Transoral endoscopic thyroidectomy in the thyroid cancer in children

BACKGROUND: Transoral endoscopic thyroidectomy (TE) by the vestibular access is an advanced technique in modern domestic oncology as it enables to have a perfect cosmetic results without any asymmetry caused by the scar strain on the visualized surface of the neck skin. CLINICAL CASE DESCRIPTION: The article presents the first Russian experience, obtained in the research and clinical institution specializing in oncological diseases, in the application of transoral endoscopic TE by the vestibular access in children suffering of differentiated thyroid cancer. 9 children with thyroid cancer (TC), who were hospitalized to the A. Tsyb Medical Radiological Research Center from July 5, 2022, till December 20, 2022, were taken in the study. Tumor stage was estimated by the International Classification TMN TC (UICC, 8th ed., 2017): cT1a — 6 patients, cT1b — 3 patients. The age ranged from 6 to 17 y.o., average 15.2±1.1 (5 boys, 4 girls). All patients survived endoscopic surgery on the thyroid gland (TG) by the vestibular access: 6 patients — hemithyroidectomy (HTE) and 3 patients — TE, selective cervical lymphadenectomy (level VI). All nine endoscopic surgeries on the thyroid gland by the vestibular access were successful, without conversion. In all patients, paratracheal, pretracheal and prelaryngeal groups of lymph nodes on the lesion side (level VI) were removed. Surgery duration ranged from 59 to 143 minutes, average 95±20.5 minutes. No complications, such as laryngeal nerve paresis or hypoparathyroidism, were observed. Intradermal hematoma and chin skin paresthesia were registered as local postoperative complications which did not require any treatment. All patients were satisfied with their cosmetic outcomes. CONCLUSION: Transoral endoscopic thyroidectomy by the vestibular access is a safe and feasible alternative surgical intervention for neoplasms in the carefully selected infants so as to avoid scar formations on the frontal neck surface. Transoral endoscopic interventions in the thyroid gland and regional lymphatic regions by the vestibular access should be performed only in highly specialized oncological centers equipped with modern endoscopic devices.

Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.

Integral evaluation of thyroid lymphatic region in phytocorrection of hypothyroidism consequences

To date, the integrative involvement of thyroid lymphatic region structures in providing tissue homeostasis in hypothyroidism and during rehabilitation remains a poorly understood problem. The use of phytotherapy is attractive for reducing the effects of hypothyroidism. This issue requires scientific justification during the rehabilitation phase.Material and methods. The work was performed on 160 white Wistar rats using light and electron microscopy according, data of morphometry and statistical matrix analysis. An adequate model of hypothyroidism was created by mercazolil administration. After the mercazolil withdrawal, we investigated the reversibility of thyroid and regional lymph node changes during the rehabilitation period (on 7, 14, 21 days) on the background of bioactive phytocomposition intake and without it. Phytocomposition from laminaria and medicinal plants of Siberia was used at a dose of 0.2 g/kg for three weeks after the cancellation of mercazolil.Results and discussion. The study showed a unidirectional change in thyroid and lymph node structure with a preferential decrease in indicators in hypothyroidism. The value of the total normalized index for the lymphatic region (lymphothyroostat) is negative during the recovery period without phytocorrection. The index has a negative value initially and up to 14 days and becomes positive only by the end of 21 days of the study reflecting the inertia of the structural response of organs. Phytotherapy provides high rationed index rates for lymphothyrostat. The index becomes positive starting at day 14. There is an intensification of compensatory and adaptive reactions at all levels of lymphothyrostat organization, starting with ultrastructural. The lymph node contributes significantly to the provision of homeostasis of the lymph region of the thyroid gland.Conclusions. Reorganization of the lymph node and thyroid gland is interconnected in hypothyroidism. The active role of the lymph node in providing tissue homeostasis in the lymph region of the thyroid is apparent. Thyroid and lymph node function can be enhanced by phytotherapy. Phytocomposition reduces the effects of hypothyroidism. It is a kind of modifier of thyroid and lymph node structure and function

Evaluating Panchvalkala Ointment’s Healing Properties in Suppurated Cervical Lymphadenitis: A Case Report

An inflammatory or non-inflammatory enlargement of the lymph nodes is known as lymphadenopathy. The prevalence of lymphadenopathy illnesses increases with age. In Ayurveda, lymphadenopathy is generally described as five diseases, namely Arbuda (Tumor), Granthi (Cyst), Apachi (Cervical lymphadenitis), Gandamala (scrofula), and Pashangardabh (Temporomandibular inflammation). The case described here is Apachi. Acharyas focused on the disease's site of occurrence while characterizing Apachi. The book described the following locations as the site of occurrence: Hanuasthi (mandible bone), Kaksha (axillary), Akshak (clavicle), Manya (neck), and Vangshan (medial aspect of thigh). These were the lymph nodes mostly superficial lymphatic outflow regions. The method followed here was pre-operative medications followed by surgical management, i.e., Bhedana (Incision) leading to immediate drainage of tubercular cervical abscesses along with post-operative management and successive dressing of the wound until complete healing of the cavity through Ayurvedic Panchavalkal ointment. The problem was completely cured as a result of the prescribed Wound care ointment treatment followed by Incision and Drainage. This case study described how to successfully combine surgical and Ayurvedic treatment to treat Manyagata Apachi, or tubercular cervical lymphadenitis, which developed into an abscess. Suppurative cervical lymphadenitis is a frequently encountered condition with various aetiologies. Early recognition, Accurate diagnosis, and appropriate management are essential to prevent complication and promote optimal patients’ outcomes.

The role of micrometastasis in high-risk skin cancers.

The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.

Proton Therapy in the Treatment of Men with Breast Cancer

PurposeMale breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and MethodsMen who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. ResultsFive male patients were identified. All had estrogen receptor (ER)–positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41–80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0–1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0–14.2), and median follow-up was 2 years (range, 0.75–6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. ConclusionIn a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing.

Impact of Radiotherapy Volumes on Late-Term Cosmetic Outcomes and Quality of Life in Patients With Unifocal and Multifocal/Multicentric Breast Cancer After Breast-Conserving Surgery.

Breast-conserving surgery (BCS) followed by radiotherapy (RT) is the standard treatment for early-stage breast cancer. The use of an additional RT dose (boost) to the tumour bed improves local control but may worsen quality of life (QOL) and cosmetic results. Multifocal/multicentric tumours (MMTs) pose a challenge as they require larger boost volumes. This study investigated the impact of RT volumes on late-term cosmetic outcomes and QOL in patients with unifocal and MMTs who underwent adjuvant RT after BCS. Retrospective data of 367 patients who underwent BCS between 2012 and 2014 were reviewed. A cohort of 121 patients with at least six months of completed RT were prospectively included in the study. Cosmetic results were evaluated using a modified scoring system, and QOL was assessed using The European Cancer Treatment and Organization Committee tools. The results showed that the inclusion of regional lymphatics in the RT treatment field significantly affected QOL, particularly in terms of role functioning and social functioning. Higher boost volume ratios were associated with increased pain-related symptoms. However, the presence of MMTs did not significantly affect cosmetic outcomes compared to unifocal tumours. The size of the boost and inclusion of regional lymphatics in RT significantly impact QOL in patients undergoing BCS. Tumour foci number does not affect cosmetic outcomes. These findings emphasize the need for careful consideration of RT volumes to minimize long-term adverse effects on QOL. Future prospective studies should evaluate early side effects and baseline QOL scores to provide a comprehensive assessment.

ОЦЕНКА ЭФФЕКТИВНОСТИ ИСПОЛЬЗОВАНИЯ РЕГИОНАРНОЙ ЛИМФОТРОПНОЙ ТЕРАПИИ ПРИ ЭКССУДАТИВНОМ СРЕДНЕМ ОТИТЕ В ЭКСПЕРИМЕНТЕ

In lymphology, there is a great potential of knowledge about the role of the lymphatic system in the implementation of water homeostasis, as one of the most important factors of the constancy of the internal environment of the body, drainage, and detoxification of tissue fluid and lymph. The lymphatic system is one of the first to react to the inflammatory process in any region of the human body; therefore, an obligatory element of the standard of examination of patients is to assess the condition of regional lymph nodes. At the same time, the lack of data on the involvement of the lymphatic system in the development of exudative otitis media hinders the development of new pathogenetically sound modern methods of lymphotropic therapy of one of the diseases common in otorhinolaryngology. In this work, the features of structural transformations of different groups of neck lymph nodes (superficial, facial, deep) belonging to the lymphatic region of the middle ear are studied and shown under physiological conditions, when modeling exudative otitis media and after lymphotropic therapy involving the introduction of a mixture of drugs into tissues using low-frequency ultrasound. According to the degree and nature of the response of the structural components of the nodes to the modeling process in the experiment of exudative inflammation in the middle ear and therapeutic measures aimed at lymphosanation, nodes of the first order – deep lymph nodes, and of the second order – superficial lymph nodes were identified. Therapy aimed at the rehabilitation of the lymphatic region of the middle ear and associated cavities leads to complete normalization of the lymph nodes and relief of inflammatory processes, therefore it can be considered pathogenetically justified.

Comparative Study of Hypofractionated Palliative Radiotherapy 17 Gy in 2 Fractions vs. 30 Gy in 10 Fractions in Lethal Locally Advanced Non-small Cell Lung Cancer

<i>Background</i>: Lung cancer kills the most people worldwide. Most Bangladeshi patients had regionally advanced surgically inoperable Non-Small Cell Lung Cancer (NSCLC), a deadly disease. Radiotherapy to main tumor and regional lymphatics with chemotherapy is conventional treatment. <i>Objective</i>: This study was done to investigate the symptoms relief and treatment related toxicities in hypo fractionated 17 Gy in 2 fractions which is effectively comparable to 30 Gy in 10 fractions. <i>Methods</i>: A total 60 patients were divided equally into Arm A and Arm B with locally advanced stage IIIA, and stage IIIB NSCLC patients with the objective to compare palliation of symptoms and to assess the toxicity profile. This Quasi Experimental study was carried out from January 2018 to December 2018 in the department of Radiation oncology, National Institute of Cancer Research and Hospital. Cases of Arm A were treated with 17 Gy radiotherapy in 2 fractions and those of Arm B were treated with 30 Gy radiotherapy in 10 fractions. <i>Results</i>: The mean age was 49.3±8.8 and 52.2±8.1 years for the Arm- A and the Arm-B respectively. Most patients in both groups were males, 80% in group A and 90% in group B. Adenocarcinoma (Arm A-70%, Arm B- 66.7%) was the most common pathological subtype in both groups, followed by Squamous cell carcinoma (30%, 33.3% respectively). This study showed that there was a significant palliation of these symptoms following radiotherapy as reported by patients and as assessed clinically with no statistically significant difference between two Arms. Hemoptysis had the highest rate of improvement, 100% in both arms and improvement in chest pain by 83.3% in arm A and 70% in Arm B. Cough was improved in 83.3% and 67.7% and dyspnea was palliated in 80.0% and 70.0% of patients in Arm A and Arm B, respectively as per clinical assessment of the patients. The early toxicities in both arms had no significant difference. Patients with locally advanced inoperable NSCLC have poor prognosis and less survival. The first goal was acceptable symptoms control as cough, dyspnoea, haemoptysis and chest pain. <i>Conclusion</i>: The result of this study showed that a significant palliation of symptoms with minimum toxicities improving quality of life following radiotherapy as reported by patients also assessed clinically and radiographically with no statistically significant difference among both arms.

The lymphatic system of the uterine cervix: towards a more precise definition of the drainage routes

Lymph node involvement in cancer of the uterine cervix is a major independent prognostic factor for overall survival. The aim of our study was to examine the lymphatic drainage regions of the different parts of the uterine cervix. An anatomical study of fresh cadavers was conducted by injecting patent blue in the anterior or posterior lip of the uterine cervix and dissecting drainage regions. Furthermore, a retrospective radiological and pathological studies were conducted on patients who were treated for early-stage cancer of the uterine cervix with lymph node involvement. Radiological analysis of pre-therapeutic MRIs and/or pathological analysis of surgical specimens showed the precise location of the tumour. A correlation between the anatomy of the primary lesion site and the lymphatic area involved was established. We administered 15 cadaveric injections: 8 in the anterior lip of the uterine cervix and 7 in the posterior one. For 100% of the anterior lip injections, lymphatic drainage was bilateral ileo-obturator (n = 8/8) combined with bilateral parametrial drainage. For the posterior injections, there was never any ileo-obturator drainage, and 6 of the 7 (75%) posterior injections drained in the posterior uterine serosa. Concerning the clinical study, we included 21 patients. We observed a non-significant tendency towards bilateral lymph node involvement when the tumour of the anterior lip. Physiological lymphatic drainage of the uterine cervix presents anatomical specificities, depending on the structure studied, anterior or posterior lip of the cervix. Better knowledge of these specificities should allow personalized surgery for each patient.

Incidence of Rib Fracture following Treatment with Proton Therapy for Breast Cancer.

To determine the rib fracture rate in a cohort of patients with breast cancer treated with proton therapy. From a prospective database, we identified 225 patients treated with proton therapy between 2012 and 2020 (223 women; 2 men). Clinical and dosimetric data were extracted, the cumulative incidence method assessed rib fracture rate, and Fine-Gray tests assessed prognostic significance of select variables. In-field rib fracture was defined as a fracture that occurred in a rib located within the 10% isodose line. Out-of-field rib fracture was defined as a fracture occurring in a rib location outside of the 10% isodose line. Of the patients, 74% had left-sided breast cancer; 5%, bilateral; and 21%, right-sided. Dual-energy x-ray absorptiometry scans showed normality in 20%, osteopenia in 34%, and osteoporosis in 6% (test not performed in 40%). Additionally, 57% received an aromatase inhibitor. Target volumes were breast ± internal mammary nodes (IMNs) (16%), breast and comprehensive regional lymphatics (32%), chest wall ± IMNs (1%), and chest wall/comprehensive regional lymphatics (51%). Passive-scattered proton therapy was used for 41% of patients, 58% underwent pencil-beam scanning (PBS), and 1% underwent a combination (passive scattering/PBS), with 85% of patients receiving a boost. Median follow-up was 3.1 years, with 97% having >12-month follow-up. The 3-year cumulative in-field rib fracture incidence was 3.7%. Eight patients developed in-field rib fractures (1 symptomatic, 7 imaging identified) for a 0.4% symptomatic rib fracture rate. Median time from radiation completion to rib fracture identification was 1.8 years (fractures were identified within 2.2 years for 7 of 8 patients). No variables were associated with rib fracture on univariate analysis. Three fractures developed outside the radiation field (0.9% cumulative incidence of out-of-field rib fracture). In this series of patients with breast cancer treated with proton therapy, the 3-year rib fracture rates remain low (in-field 3.7%; symptomatic 0.4%). As in photon therapy, the asymptomatic rate may be underestimated owing to a lack of routine surveillance imaging. However, patients experiencing symptomatic rib fractures after proton therapy for breast cancer are rare.

Abstract P1-10-08: Incidence of rib fracture following treatment with proton therapy for breast cancer

Abstract Purpose: To determine the rate of rib fracture in a cohort of patients with breast cancer treated with proton therapy and enrolled on a prospective registry. In series investigating photon therapy for breast cancer, the rib fracture rate ranges from 0.3-13% Methods: From a prospective database, we identified patients treated with proton therapy for breast cancer at our institution between January 1, 2012 and December 31, 2020. Clinical and dosimetric data was extracted from the electronic medical record. The cumulative incidence method assessed rib fracture rate; the Fine-Gray test statistic assessed prognostic significance select variables. Results: 225 patients were identified, 223 women and 2 men. Median age at the time of radiation was 57.8 years (range, 25 – 87). 26% of patients were black, 69% white and 5% were other races or race not disclosed. 5% were Hispanic. 74% of patients had left-sided breast cancer, 5% bilateral, and 21% right-sided. DEXA scan was normal in 20%, showed osteopenia in 34%, osteoporosis in 6%, and not performed in 40%. 57% of patients received antiendocrine therapy with an aromatase inhibitor. For 16% of patients, the breast +/- internal mammary nodes (IMN) were treated, while 32% underwent proton therapy to treat the breast and comprehensive regional lymphatics. 1% of patients had chest wall +/- IMN treated, while 51% underwent proton therapy to treat the chest wall and comprehensive regional lymphatics. 41% of patients were treated with passive scatter proton therapy (n=92); 52% of these had mastectomy. 58% of patients received treatment with pencil beam scanning (PBS) proton therapy (n=131); 53% of these had mastectomy. A combination of passive scatter and PBS was used for 2 patients (1%). 85% of patients received a boost. Median follow-up was 3.1 years (range, 0.2 – 9.1). 97% of patients had &amp;gt; 12 months of follow-up. The 3 year cumulative incidence of in-field rib fracture was 3.7% (95%CI: 1.6%-7.1%). In total, 8 patients developed in-field rib fractures, one symptomatic and 7 identified incidentally on surveillance imaging, for a 0.4% rate of symptomatic rib fracture. Median time from completion of radiation to identification of rib fracture was 1.8 years (range, 0.4-7.4 years). Rib fractures occurred within 2.2 years from radiotherapy completion for seven of the eight patients who experienced this side effect. Three patients developed rib fractures outside of the radiation field, for a cumulative incidence of out-of-field rib fracture of 0.9% (95%CI: 0.2-3.0%). No variables were associated with rib fracture on univariate analysis. Of those with in-field rib fractures, 3 had low and 3 had normal bone density while 2 had not undergone testing; of those with out-of-field rib fractures, 2 had osteopenia and 1 did not have testing. Conclusions: Although a proton beam has higher biological dose deposition at end-of-range than the assumed constant RBE=1.1, the 3 year rate of any in-field rib fractures in our series remains low at 3.7%, with a 0.4% rate of symptomatic rib fracture. Contouring ribs as an OAR and establishing a dose constraint warrants further investigation as a means to maintaining a low rate of rib fracture with proton therapy. Citation Format: Julie Bradley, Xiaoying Liang, Raymond Mailhot Vega, Chunbo Liu, Eric Brooks, Teena Burchianti, Emma Viviers, Roi Dagan, Oluwadamilola Oladeru, Christopher Morris, Nancy Mendenhall. Incidence of rib fracture following treatment with proton therapy for breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-08.

Microbubble contrast agent SonoVue: An efficient medium for the preoperative lymphatic mapping of thyroid carcinoma.

Objective: To assess the value of microbubble contrast agent SonoVue in the thorough preoperative lymphatic mapping of patients with thyroid carcinoma, including the lymphatic drainage region, the detection of sentinel lymph node (SLN), and the diagnosis of lymph node metastasis (LNM). Materials and methods: 55 patients with 62 thyroid malignancies proved by surgical pathology (59 papillary thyroid carcinomas and three medullary thyroid carcinomas) who underwent preoperative lymphatic contrast-enhanced ultrasound (LCEUS) with microbubble contrast agent SonoVue were enrolled. All LNM were confirmed by pathology. The location of thyroid lesions, ultrasonic features of lymph nodes, lymphatic drainage region, and detection of SLN were assessed. The diagnostic performance (sensitivity, specificity, positive predictive value, negative predictive value and accuracy) of different parameters for the LNM diagnosis was calculated. Results: SonoVue effectively demonstrated the lymphatic drainage region for all enrolled thyroid carcinomas. The most common lymphatic drainage region for thyroid carcinomas was region VI (93.55%), followed by region III (62.90%), region IV (48.39%) and region II (4.84%). When divided by the lesion location, the most common lymphatic drainage regions for the nodule in isthmus, superior lobe and inferior lobe of the thyroid were region VI, region III, and region VI respectively. SLN was detected in 96.77% (60/62) of cases. The two cases without SLN demonstration had pathologically proven LNM. The most common sonographic sign of LNM was perfusion defect (54.17%). The diagnostic accuracy of SonoVue in central and lateral compartment LNM was 86.67% and 91.67%, respectively. Conclusion: Microbubble contrast agent SonoVue is a valuable imaging contrast medium for thorough preoperative lymphatic mapping in patients with thyroid carcinoma, including the lymphatic drainage region, the detection of SLN, and the diagnosis of LNM. LCEUS with SonoVue alone has limitations of false negatives when there is lymphatic vessel obstruction and may need to be combined with other ultrasound modalities.

Proton therapy for isolated local regional recurrence of breast cancer after mastectomy alone.

To assess adverse events (AEs) and disease-specific outcomes after proton therapy for isolated local-regional recurrence (LRR) of breast cancer after mastectomy without prior radiotherapy (RT). Patients were identified from a multi-institutional prospective registry and included if diagnosed with invasive breast cancer, initially underwent mastectomy without adjuvant RT, experienced an LRR, and subsequently underwent salvage treatment, including proton therapy. Follow-up and cancer outcomes were measured from the date of RT completion. Nineteen patients were included. Seventeen patients were treated with proton therapy to the chest wall and comprehensive regional lymphatics (17/19, 90%). Maximum grade AE was grade 2 in 13 (69%) patients and grade 3 in 4 (21%) patients. All patients with grade 3AE received > 60 GyE (p=0.04, Spearman correlation coefficient=0.5). At the last follow-up, 90% of patients were alive with no LRR or distant recurrence. For breast cancer patients with isolated LRR after initial mastectomy without adjuvant RT, proton therapy is well-tolerated in the salvage setting with excellent loco-regional control. All grade 3 AEs occurred in patients receiving > 60 GyE.

IS TOXOPLASMA A DIFFERENTIAL IN SUPERFICIAL LYMPH NODE ASPIRATES SHOWING GRANULOMATOUS PATHOLOGY?

Background: Peripheral lymphadenopathy is frequently due to a local or systemic, benign, self-limited, infectious disease or malignancy. Cervical lymph nodes are involved more often than the other lymphatic regions. In India tuberculosis (TB) is a major benign cause in adults and children. Some studies have been conducted to assess sero prevalence of toxoplasmosis, another infectious disease of signicance. The clinical overlap of spectrum between various diseases like early TB, sarcoidosis and toxoplasmosis has led us to investigate in this grey zone. Methodology: FNAC from enlarged cervical nodes of 100 patients was done. DNA extraction from the aspirate and Antigen –antibody reaction (ELISA) on serum samples was done on 49 patients who showed granulomatous pathology on cytology smears, out of 100 samples collected. Results: There were no IgM antibodies detected in any serum sample. IgG was detected in 7 cases. PCR on the lymph node aspirates did not show any presence of B1 gene of Toxoplasma. We recommend that a differential of Toxoplas Conclusion: ma be kept as a possible diagnosis when Zeihl Neelsen does not detect AFB on the granulomatous lymphadenopathies. Serologic conrmation in all suspected cases of this self-limited condition should be done, for which no treatment is necessary

Study of Linear Energy Transfer Effect on Rib Fracture in Breast Patients Receiving Pencil-Beam-Scanning Proton Therapy

<h3>Purpose/Objective(s)</h3> To study the linear energy transfer (LET) effect upon rib fracture (RF) in breast cancer patients treated with pencil-beam scanning proton therapy (PBS) using dose-linear energy transfer volume histogram (DLVH). <h3>Materials/Methods</h3> After IRB approval, we retrospectively identified RF cases detected after workup of chest wall pain or incidentally on imaging in breast cancer patients treated with PBS to the breast/chest wall and regional nodes from 2015-2020. Control patients were selected to match the RF patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year. For all plans, a chest wall was contoured, incorporating ribs and intercostal muscles within the 50% prescription isodose line. Both dose and LET were calculated using a planning tool dose engine. DLVH was generated for each patient, using dose and LET as the two axes. The DLVH index, <i>V</i>(<i>d, l</i>), defined as <i>V</i>(% for normalized volume or cc for absolute volume) of the structure with a dose of at least <i>d</i> Gy[RBE] and an LET of at least <i>l</i> keV/µm, was calculated for all combinations of <i>d</i> and <i>l</i>. Conditional logistic regression model was used to establish the relation of <i>V</i>(<i>d, l</i>) and the observed RF at each combination of <i>d</i> and <i>l</i>. The derived <i>p values</i> constitute a <i>p value</i> map in the 2D dose and LET plane. Concordance and its standard error (se) maps were generated to evaluate the performances for all DLVH indices. A correlation coefficient map was obtained to determine the correlation between the featured DLVH indices. <h3>Results</h3> Eight RF cases were identified, and 16 controls were matched. Of RF patients, seven were treated with post-mastectomy (PMRT) and one was treated with post-lumpectomy radiotherapy. Six RF patients treated with PMRT received a dose of 50 Gy[RBE] in 25 fractions to the chest wall and regional lymph nodes; of these, four received a simultaneous integrated boost (SIB) of 56.25 Gy[RBE] to the chest wall (n=2) or axillary nodes (n=2), and one received a sequential boost of 14 Gy[RBE] in 7 fractions to the chest wall. One RF patient that received PMRT was treated with 40.05 Gy[RBE] in fifteen fractions to the chest wall and regional lymphatics. The post-lumpectomy patient received 50 Gy[RBE] in 25 fractions to the whole breast and regional nodes with a SIB of 56.25 Gy[RBE] to the lumpectomy cavity. Two characteristics correlated with RF (<i>p</i><0.2): 1) Smaller <i>V</i>(50-54 Gy[RBE], 0-4.4keV/µm) of the RF patients with a maximum concordance of 0.813 (se 0.114); 2) Larger <i>V</i>(0-36 Gy[RBE], 5.2-6.8keV/µm) of the RF patients with a maximum concordance of 0.875 (se 0.119) compared with controls. These two features were independent from each other with a weak negative correlation (-0.185). <h3>Conclusion</h3> The increase of high LET in moderate dose regions of the chest wall from constraining the adjacent heart and lung dose during PBS treatment planning may result in increased risk of RF.