Regional Recurrence Research Articles

Prognosis for local radical treatment in patients with esophageal squamous cell carcinoma with low-risk oligometastatic recurrence after curative resection: a retrospective cohort study.

Patients with esophageal carcinoma (EC) with recurrent disease have a poor prognosis. A limited numbers of metastases, safely treatable with curative intent, diagnosed after curative esophagectomy may be defined as oligometastatic recurrence (OLR). However, the appropriate number of metastases and metastatic organs involved remains incompletely characterized. And the role of local therapy in OLR after radical esophagectomy remains unknown. Therefore, this study aimed to more accurately define low-risk OLR in patients with esophageal squamous cell carcinoma (ESCC) treated with radical resection and investigate the role of chemotherapy combined with local treatment (CCLT) in these patients. A total of 83 sequential patients with ESCC who underwent radical esophagectomy, with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with ability to tolerate chemotherapy (CT) and local treatment, and with newly diagnosed recurrence between January 2010 and May 2019 in our hospital were recruited. Overall survival (OS) curves after recurrence were analyzed using the Kaplan-Meier method, and a log-rank test was used to assess the OS differences. Cox proportional hazards regression analysis was performed to identify independent factors associated with 2-year OS. Regular follow-up examinations were assessed by thoracic and upper abdominal computed tomography (CT) scanning every 3 months in the first year, every 6 months over the next 2 years, and yearly thereafter. Of the 83 patients with ESCC (71 males and 12 females), the median age was 56 years (range, 37-79 years). Thirty-five patients with ESCC with ≤5 metastases safely treatable with curative intent located in a single organ had a favorable OS compared to 48 patients with metastases located in 2-3 organs with or without regional recurrence and/or regional lymph node (LN) metastases. In our study, low-risk OLR was defined as the presence of ≤5 metastases safely treatable with curative intent in a single organ and was compared to patients with 2-3 organs involved. The 2-year OS of patients with low-risk OLR with liver oligometastases was significantly worse than survival in patients with lung oligometastases (0% vs. 61.1%, P=0.009). Patients with ESCC in the low-risk OLR group treated with CCLT had a better 2-year OS after recurrence than those who received CT alone (66.7% vs. 30.4%, P=0.003). The multivariable Cox regression model identified treatment method [hazard ratio (HR) 3.920, P=0.02] as an independent factor affecting OS after recurrence for low-risk OLR. Low-risk OLR was defined as ≤5 metastases safely treatable with curative intent in a single organ. Patients with ESCC with low-risk OLR after curative resection treated with CCLT have a favorable OS compared to those treated with CT alone. CCLT is a promising treatment option for patients with ESCC and low-risk OLR.

FGD-PET/CT three months after (chemo)radiotherapy for head and neck squamous cell carcinoma spares considerable number of patients from a salvage neck dissection

PurposeIn the last decades FDG-PET/CT is increasingly used in combination with the standard diagnostic modalities (MRI + US-FNA) to identify residual neck disease (RND) after (chemo)radiotherapy for head-and-neck squamous cell carcinoma (HNSCC). The purpose of the current study is to identify the impact of increasing use of FDG-PET/CT on the accuracy of patient selection for salvage neck dissection (SND). Materials and methodsBetween 2008 and 2022, 908 consecutive patients with node-positive HNSCC were treated with (chemo)radiotherapy in our institution. Primary endpoint: positive predictive value (PPV) of FDG-PET/CT for pathologic-confirmed RND (pRND) after SND, compared to the standard of care; MRI + US-FNA. Secondary endpoints: oncologic outcomes. ResultsOf the entire group, 130 patients (14 %) received SND. Of them only 53 patients (41 %) had pRND at the SND-specimens. The PPV of FDG-PET/CT for the detection of pRND was considerably better, compared to MRI + US-FNA; 89 % and 65 %, respectively. If FDG-PET/CT showed metabolic CR, these patients did not undergo SND. The NPV was 97.5 %, as only 2.5 % of these patients developed delayed regional failure.FDG-PET/CT considerably improved the accuracy of patient selection for SND, as significantly more patients treated in the second period, compared to first period of the study (n = 454 each) still had vital tumor at SND-specimen (53 % and 31 %, p = 0.008). Regional recurrence free-survival, DFS, OS and HNSCC-death were significantly worse in patients with pRND (p < 0.05) ConclusionsIncorporating FDG-PET/CT into the diagnostic pathway for the response evaluation after (chemo)radiotherapy significantly improved the accuracy of patient selection for SND and spared considerable number of patients (>20 %) from unnecessary SND. For patients with metabolic CR, SND can safely be omitted while for patients with no metabolic CR, SND is strongly advocated.

Predicting Regional Recurrence and Prognosis in Stereotactic Body Radiation Therapy-Treated Clinical Stage I Non-small Cell Lung Cancer Using a Radiomics Model Constructed With Surgical Data

BackgroundRisk stratification of regional recurrence (RR) is clinically important in the design of adjuvant treatment and surveillance strategies in patients with clinical stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). PurposeTo develop a radiomics model predicting occult lymph node metastasis (OLNM) using surgical data and apply it to the prediction of RR in SBRT-treated early-stage NSCLC patients. MethodsPatients with clinical stage I NSCLC who underwent curative surgery with systematic lymph node dissection from January 2013 to December 2018 (the training cohort) and from January 2019 to December 2020 (the validation cohort) were included. A pre-operative CT-based radiomics model, a clinical feature model, and a fusion model predicting OLNM were constructed. The performance of the three models was quantified and compared in the training and validation cohorts. Subsequently, the radiomics model was used to predict RR in a cohort of consecutive SBRT-treated early-stage NSCLC patients from two academic medical centers. ResultsA total of 769 patients were included. Eight CT features were identified in the radiomics model, achieving areas under the curves (AUCs) of 0.85 (95% CI 0.81-0.89) and 0.83 (95% CI 0.80-0.88) in the training and validation cohorts, respectively. Nevertheless, adding clinical features did not improve the performance of the radiomics model. With a median follow-up of 40.0 (95% CI 35.2-44.8) months, 32 of the 213 patients in the SBRT cohort developed RR and those in the high-risk group based on the radiomics model had a higher cumulative incidence of RR (p<0.001) and shorter regional recurrence-free survival (p=0.02), progression-free survival (p=0.004) and overall survival (p=0.006) than those in the low-risk group. ConclusionThe radiomics model based on pathologically confirmed data effectively identified patients with ONLM, which may be useful in the risk stratification among SBRT-treated patients with clinical stage I NSCLC.

Recurrence Patterns of Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck.

The objective of this study was to describe risk factors and recurrence patterns that can guide the creation of evidence-based surveillance guidelines for advanced cutaneous squamous cell carcinoma of the head and neck. This was a single-institution retrospective case series. High-volume academic head and neck surgical oncology practice. Patients who underwent surgery for cutaneous squamous cell carcinoma of the head and neck staged Brigham and Women's Hospital T2b and T3 from 2003 to 2023 were reviewed. Patient demographics, clinicopathologic history, cancer data, treatment, and outcomes were abstracted. Disease-free survival and risk factors for recurrence were described. A total of 183 patients were included. Fifty-six (30.6%) experienced recurrence. This included local recurrence in 21 (11.5%), regional in 21 (13.3%), and distant in 11 (6%). The majority of regional and distant recurrences occurred within 1 year of surgery. The majority of disease recurrence occurs in the first 1 to 2 years following surgical excision of advanced-stage cutaneous squamous cell carcinoma of the head and neck. Close surveillance and frequent imaging within those years are critical to catch subclinical and distant diseases.

Lymph Node Evolution in Eyelid and Orbit Squamous Cell Carcinomas.

To describe a large cohort of eyelid and periorbital SCCs, to compare the location of the tumor and of the pathological lymph nodes, and to analyze the risk factors for lymph node involvement among tumor characteristics. All patients managed inside our institution for an eyelid and periorbital SCCs were included. Tumor characteristics, imaging setup, excision margins, lymph node evolution features, local, regional, and distant recurrences rates, and global survival were reported. The risk for lymph node involvement and location of pathological lymph nodes were analyzed through univariate and multivariate analyses. Between January 2012 and August 2022, 115 patients were included, and 18 presented a lymph node evolution (15.7%), involving the parotid gland in 16 cases (88.9%), the submental and submandibular areas in seven cases (38%), and the jugular and carotid areas in four cases (22%). Tumor size above 20 mm, infiltration of the external canthus and periorbital structures, the presence of perineural invasion or vascular embolism, the depth of infiltration, and the presence of a local recurrence were significantly associated with the risk of lymph node evolution. Periorbital and eyelid SCCs present a true potential for lymph node evolution especially through the parotid gland. Extension setup including the parotid gland and neck should be mandatory, and lymph node dissection should be associated in case of parotidectomy for lymph node involvement. IV Laryngoscope, 2024.

Treatment of sebaceous carcinoma with Mohs micrographic surgery versus wide local excision: a systematic review

AbstractSebaceous carcinoma (SC) is a rare neoplasm affecting periocular and extraocular sites. If inadequately treated, it can recur and cause morbidity. Specific management guidelines have not been established. Wide local excision (WLE) has been traditionally used; however, Mohs micrographic surgery (MMS) can be advantageous because of complete margin assessment and tissue‐sparing nature. This analysis aims to systematically review the surgical modalities used for the management of SC. Articles meeting eligibility criteria were identified using MEDLINE (via PubMed), Embase, Cochrane, and Scopus databases. All studies investigating surgical management of SC with WLE or MMS were considered. Seventy studies met inclusion criteria, including retrospective cohort studies, case series, and case reports. WLE was used in 32 studies, MMS in 29, and MMS and WLE in 9. Subgroup analysis showed that MMS has lower recurrence rates. For WLE, local, regional, and distant recurrence rates were 23.4%, 13.3%, and 11.0%, respectively, and for MMS, 6.8%, 4.3%, and 4.6%, respectively. Patients treated with WLE were more likely to have local recurrence than patients treated with MMS (P = 0.001). WLE cases were more likely to have a regional (P = 0.05) and distant recurrence (P = 0.001). Limitations of the study include heterogeneity of case reports, case series, and retrospective studies, variable follow‐up times between the two groups, and large tumors included in the WLE category. In addition, disease‐specific survival was not evaluated. MMS cases showed a superior outcome for local, regional, and distant recurrence, making it a good option for the management of SC.

The role of histology on the outcome of sinonasal carcinomas treated with radiotherapy: a single institution experience.

Sinonasal malignancies are a rare group of head and neck cancers. We aimed to report the oncological outcomes based on histological types in patients who underwent radiotherapy. In this single-institution study, we retrospectively retrieved and analyzed data of patients with sinonasal carcinomas who underwent radiotherapy during 2011-2016 as part of their treatment. The 3-year rate of local, regional, and distant recurrences, and overall survival were evaluated according to the histological type. A total of 28 patients were evaluated in this study, the majority of whom were male (60%). Squamous cell carcinoma (SCC), adenoid cystic carcinoma (ACC), and adenocarcinoma (ADC) were found in 15 patients (53.5%), 8 (28.5%), and 5 (18%), respectively. The highest rates of local and regional recurrences were observed in ACC and SCC, respectively. Distant recurrences were numerically more common in ADC. The 3-year OS was 48%, 50%, and 73% in SCC, ADC, and ACC, respectively. Different histopathologies of sinonasal cancer seem to have different patterns of failure, and this may be considered in the treatment approach.

Efficacy and safety of the combination of tisleizumab with chemoradiotherapy in oligorecurrence esophageal squamous cell carcinoma: A prospective phase II study.

4057 Background: The postoperative recurrence and metastasis rate of esophageal squamous cell carcinoma (ESCC) remains high and prognosis is poor. PD-1 immune checkpoint inhibitors have shown efficacy in targeting advanced esophageal cancer. This phase II study aims to explore the efficacy and safety of concurrent chemoradiotherapy and immunotherapy for ESCC patients with oligometastatic recurrence after radical surgery. Methods: This phase II study enrolled ESCC patients from 3 hospitals in China, diagnosed oligometastatic recurrence after radical surgery. The 1st stage, with 10 patients enrolled, was designed to explore the safety level and the 2nd stage was to explore efficacy. The oligorecurrence is defined as progression occurring three months after the operation with no more than three metastatic regions. The local recurrence was defined as tumor bed or anastomotic recurrence. The regional lymph node recurrences were regarded as mediastinal region and celiac lymph, respectively. The distal recurrences were considered as supraclavicular, retroperitoneal region and other distal organs. All of the positive regional lymph nodes were collectively counted as one lesion if regional lymph node recurrences existed. Tisleizumab was delivered on D1,22. Nab-paclitaxel 150mg/m2 (starting on D2,23) and cisplatin, 75mg/m2(starting on D2-4,22-24) were administered for two cycles. The radiotherapy was delivered with 50.4-60Gy, 1.8-2Gy per fraction. After CRT, patients received Tisleizumab every 3 weeks for 3-6 months and 2-4 cycle consolidation chemotherapy. The primary endpoint was 1-year OS, the second endpoints were 1-year PFS, ORR and toxicities. Results: Between Jan 2021 and May 2023,50 patients were screened for enrolment and 44 patients met the eligibility criteria. The metastatic regions were made up by the local (15.9%),regional (47.7%), distal (13.6%) and mixed recurrence (22.7%). In the 1st stage, one patient had a grade-3 Immune-related erythra out of ten patients. All patients were delivered chemoradiotherapy, 36(81.8%) patients had completed two cycles of immunotherapy. The ORR rate was 84.1%. During concurrent chemoradiotherapy, the incidence of grade≥3 treatment-related adverse events was nausea (9.1%), vomit (4.5%), anorexia (4.5%), leukopenia (13.6%), hepatitis (2.3%), radiation esophagitis (1.4%), erythra (4.5%). There were 5 cases of Immune-related adverse, including 2 cases of erythra, 1 case of hypothyroidism, hepatitis, gastroenteritis, respectively. With the median follow-up time of 19 months (range:4-30 months), 1-year OS and PFS was 83.2% and 79.2%. The median OS and the median PFS were not reached. Conclusions: Concurrent chemoradiotherapy and immunotherapy yielded satisfactory 1-year OS rate and manageable toxicities in oligometastatic recurrence patients with ESCC after radical surgery. Clinical trial information: NCT04821765 .

Contact x-ray brachytherapy for the treatment of rectal cancer: A systematic review and meta-analysis.

e15628 Background: Rectal cancer is a highly prevalent disease, particularly among the elderly and frail populations. While surgical resection has traditionally been the primary management approach, it carries inherent risks, including operative mortality, morbidity, and poor long-term functional outcomes. These risks are particularly pronounced in older, co-morbid individuals. Evidence presented in the 2023 phase III OPERA randomised trial suggests that Contact X-ray Brachytherapy (CXB) is a viable organ-preserving alternative to radical surgery. We conducted a systematic review and meta-analysis to assess the clinical effectiveness of CXB in the treatment of rectal cancer. Methods: This systematic review was prospectively registered (CRD42021284969) and reported in accordance with PRISMA guidelines. PubMed, EMBASE, SCOPUS and Cochrane CENTRAL Libraries were interrogated using the search terms “Rectal cancer”, “Contact Brachytherapy”, and synonym terms. Literature search and data extraction were conducted by two reviewers, with recourse to a senior author for resolution of conflicts. Clinical complete response (cCR) was the primary outcome. Secondary outcomes include local regrowth, regional recurrence, salvage surgery rates, long-term disease control post-salvage surgery and survival outcomes. Proportional meta-analyses were conducted and presented as forest plots with summary proportions and 95% confidence intervals. The Higgins I2 statistic was used to assess for heterogeneity. The random effects model was employed in studies reporting substantial heterogeneity (I2&gt; 50%). Results: The literature search identified 973 studies, of which 48 studies encompassing 5,447 patients were included in the meta-analysis. Pooled estimates of outcomes were as follows: cCR rate = 80% (95% CI 76-88%), local regrowth = 15% (95% CI 12-18%), regional failure rate = 3% (95% CI 2-4%), salvage surgery rate = 14% (95% CI 11-18%), long-term disease control post-salvage surgery rate = 88% (95% CI 78-96%) and organ preservation 82% (95% CI 75-88%). A subgroup analysis was conducted and stratified by concomitant therapy (CXB alone, CXB &amp; EBRT, CXB &amp; EBCRT). CXB, in conjunction with EBCRT, leads to a statistically significant reduction in both local regrowth and regional failure. The local regrowth rates were 16% (95% CI 11-21%), 17% (95% CI 11-23%), and 10% (95% CI 8-13%) respectively, with a p-value of 0.05. The regional failure rates were 4% (95% CI 2-8%), 4% (95% CI 2-5%), and 1% (95% CI 0-2%), p = 0.02. Conclusions: CXB, combined with EBCRT, in the appropriately selected patient can achieve long-term disease control whilst avoiding major surgery. Salvage surgery is a viable option for patients who experience disease regrowth, with excellent long-term disease control. CXB may be considered a safe alternative to surgery in the appropriately selected patient.

A comparative study on quality of life of patients with breast cancer receiving subcutaneous gland resection combined with primary prosthesis implantation: Minimally invasive versus open surgery.

e12597 Background: Subcutaneous gland resection of the breast combined with primary prosthesis reconstruction is mostly used for reconstruction of early breast cancer (EBC) patients. In this study, we compared the long-term quality of life (QOL) of patients who underwent these procedures in a minimally invasive or open approach. Methods: The baseline data of EBC patients who underwent subcutaneous gland resection of breast combined with primary prosthesis reconstruction in a minimally invasive or open approach from 2008 to 2020 were retrospectively analyzed. The patients receiving minimally invasive surgery were regarded as minimally invasive group, and open surgery were regarded as open group. The BREAST-Q questionnaires were used to evaluate patients’ satisfaction with breasts, implants, animation deformity, psychosocial well-being, sexual well-being, physical well-being (chest) and breast sensation. Results: A total of 546 patients were enrolled, patients with local and regional recurrence, distant metastasis, death and prosthesis (44, 44, 22,12, respectively) were excluded, 423 patients were given questionnaires to evaluate their quality of life. Totally 226 questionnaires were recovered, with a response rate of 53.43%. Except 5 questionnaires with incomplete answers, 221 questionnaires were finally valid. There were 105 cases in the minimally invasive group, with an average follow-up time of 107.48 months (range 39-185 months), and 115 cases in the open group, with an average follow-up time of 77.97 months (range 36-188 months). The age was 43.0 [37.0, 47.0] years in all patients, 43.0[38.0, 47.0] years in the minimally invasive group and 42.5[36.8, 47.0] years in the open group. The patients in stage T1-2 accounted for 96.19% in the minimally invasive group and 97.42% in the open group, stage N0-1 accounted for 90.48% and 93.97, respectively. Prosthetic implant size showed no significant difference between two groups (220 [180, 240] cm3 vs 200 [180, 245] cm3, p=0.083). No significant difference was observed in patients’ race, education, marital status, income, job and breast size between the two groups ( p&gt;0.05). The scores of the minimally invasive group in satisfaction with breasts (54.0 [47.0, 59.0] vs 49.0 [44.8, 55.0], p&lt;0.01), animation deformity (70.0 [59.0, 100.0] vs 62.0 [57.0, 84.0], p=0.016), psychosocial well-being (66.0 [53.0, 93.0] vs 62.0 [49.0, 83.0], p=0.027), and physical well-being(chest) (48.0 [32.0, 56.0] 42.0 vs [32.0, 52.0], p=0.038) were significantly higher compared with the open group. There was no significant difference in implants, sexual well-being and breast sensation between the two groups. Conclusions: Minimally invasive subcutaneous gland resection combined with primary prosthetic implantation may improve postoperative quality of life in patients with EBC.

Association of lung cancer-associated cachexia with the metastatic spread to pleura.

12095 Background: Cancer-associated cachexia (CAC), a major contributor to mortality in patients with non-small cell lung cancer (NSCLC), is characterized by alterations in body composition. Here, we explore the associations between body composition changes and the pattern of lung cancer metastatic spread. Methods: Computer tomography (CT) images from cancer diagnosis and recurrence were used to quantify subcutaneous and visceral adipose tissue (SAT, VAT) and skeletal muscle (SKM) tissue areas at the 3rd lumbar vertebrae level, using an DAFS AI-based software, Voronoi Analytics, in 101 NSCLC pts, who relapsed after surgical treatment of the primary tumor at the Medical University of Gdansk Hospital. The decrease in SKM, SAT and VAT of more than 5% or 10% at cancer relapse was compared with the pattern of cancer recurrence. Results: The median time to recurrence after primary tumor resection was 1.6 years (0.4–6.4 years). There were 38% local or regional recurrences, 59% distant recurrences, and 13% second primary lung cancers. Among the cases with distant recurrence, there were 19% brain recurrences, 22% pleural metastases, 34% lung metastases, 17% bone metastases, and 11% cases of liver relapse. More than one site of distant recurrence occurred in 51 (50%) of patients. Loss of &gt; 5% of SKM, SAT and VAT occurred in 61%, 33% and 41% respectively. Loss of &gt;5% or &gt;10% of SKM was associated with the pleural metastases at the time of cancer recurrence, ( P &lt; 0.001). Median muscle loss was –11.6% for patients with pleural relapse and –5.3 % for patients with other metastatic locations ( P &lt; 0.001). There were no significant associations between other body composition changes and the pattern of recurrences, tumor histology or age. Conclusions: NSCLC relapse to the pleura after surgical treatment of the primary tumor, appears to be associated with a decrease in the skeletal muscle compartment. This finding may inform the design of the future studies aiming to investigate molecular correlates of sarcopenia and cancer-associated cachexia.

Burkitt lymphoma in a scalp region: a case report of it’s recurrence in a 13-year-old child

Introduction: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma characterized by chromosome 8 MYC gene translocation. It manifests in three clinical types: immunodeficiency-related, sporadic (nonendemic), and endemic (African), each differing in epidemiology and clinical behavior. Treatment typically involves enrollment in clinical trials or intensive chemotherapy regimens like R-CODOX-M/IVAC. The authors present a case of recurrent BL following treatment. Case report: A 13-year-old female presented with a gradually progressive swelling in the left parieto-occipital region. Examination revealed normal vital signs and a Glasgow coma scale, with seronegative findings on investigations. An excision of a subganglion soft tissue tumor was performed, revealing histopathological features suggestive of a small round blue cell tumor. After chemotherapy, the patient experienced a recurrence in the scalp region, diagnosed as BL. Discussion: While scarce reports exist on BL in the scalp region, cases have been documented in various body locations. Treatment strategies, including chemotherapy and surgery, have shown promising results in managing the disease and improving symptoms. Conclusion: The recurrence of BL is rare, highlighting the importance of vigilance in monitoring patients post-treatment. The authors report a case of recurrent BL in a 13-year-old female, emphasizing the need for continued research and surveillance in managing this aggressive malignancy.

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.

Personalized cell-free tumor DNA analysis for patients with HNSCC: Liquid biopsy for minimal residual disease detection in head and neck squamous cell carcinoma (LIONESS).

3010 Background: Early relapse and development of metastatic disease are some of the primary reasons for the poor prognosis of patients with head and neck squamous cell carcinoma (HNSCC). We conducted LIONESS, a single-center prospective cohort study to assess ctDNA in plasma and saliva from 76 patients with HNSCC receiving primary surgery with curative intent. Our objectives were to determine whether postoperative ctDNA detection can act as a biomarker for surgical tumor clearance and detection of molecular residual disease (MRD) and to evaluate the potential of tumor-informed ctDNA analysis for early molecular-level detection of relapse or prior to clinically confirmed recurrence. Methods: Plasma and saliva samples from 76 HNSCC patients (37% stage I/II, 63% stage III/IV; 93% p16-negative) were collected pre- and postoperatively and during clinical follow-up. Whole exome sequencing was performed on FFPE tumor tissue. Tumor-specific variants for personalized assay design (RaDaR, NeoGenomics Laboratories) were selected and used in the analysis of serial samples for evidence of MRD. ctDNA levels were correlated to tumor volumes from staging CT, as well as pathological and other clinical parameters. Results: 617 longitudinal plasma and 128 saliva samples were collected pre- and postoperatively and during clinical follow-up (median follow-up time of 805 days). In plasma, ctDNA was detected at a median estimated variant allele frequency (eVAF) of 0.036% (0.000327% - 18.43%). 34% of positive samples had ctDNA levels detected at an eVAF of ≤0.01%. Increased plasma ctDNA levels were detected postoperatively in 96% of cases with confirmed clinical recurrences (21/22) with a median lead time of 160 days (6 – 763 days). Of the remaining 54 patients with no clinically confirmed relapse, ctDNA was detected immediately postop in 7 of them. In 5 patients, adjuvant therapy resulted in persistent ctDNA clearance, while 2 patients are deceased. ctDNA was also detected in baseline saliva samples from patients with HNSCC of various anatomical locations with a 74% overlap with the corresponding plasma ctDNA profiles. There was a strong linear correlation between larger tumor volumes and higher eVAF and a trend towards higher eVAF in cases with regional and distant recurrences in comparison to local relapse. Pathological tumor stage and lymph node involvement were both strongly correlated with preoperative ctDNA shedding. Conclusions: The use of ctDNA detection in surgically treated patients with HNSCC has significant potential to guide treatment decisions, improve disease outcome and potentially spare patients unnecessary, partially invasive interventions during clinical follow-up. Our work demonstrates the feasibility of tumor-informed ctDNA assays for detection of MRD postoperatively and for monitoring for early detection of relapse.

Total neoadjuvant therapy with split-course hypofraction radiotherapy combined with CAPOX and envafolimab followed by local excision for locally advanced very low rectal cancer (TRACE-LE): An open-label, single-arm, multicenter, phase II trial.

TPS3647 Background: In the treatment of patients with locally advanced very low rectal cancer, neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is considered a standard therapeutic approach. Short-course hypofractionated radiotherapy, in combination with subsequent chemotherapy, has been shown to be comparable to long-term chemoradiotherapy in terms of neoadjuvant therapy effects in rectal cancer. Additionally, it has been observed that hypofractionated radiotherapy, when combined with programmed death L-1 (PD-L1) blockade, can enhance the immune response. This study aims to investigate efficacy and safety of organ preservation in patients with locally advanced very low rectal cancer by utilizing total neoadjuvant therapy involving split-course hypofraction radiotherapy in conjunction with CAPOX and Envafolimab (a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment). Methods: TheTRACE-LE trail is an open-label, single-arm, multicenter, phase II trial. The target sample is 72 participants. Key eligibility criteria include individuals aged 18-75, confirmed rectal adenocarcinoma, cT3-4N0/cT1-4N1-2 with lower margin ≤ 2cm from anorectal ring's upper edge (MRI) and ECOG performance status of 0-2. The treatment protocol include preoperative split-course hypofractionated radiotherapy (5×7Gy), in conjunction with 6 cycles of CAPOX chemotherapy and Enverolimab (300 mg subcutaneous injections) administered in a 3-week treatment cycle. The primary outcome measure is organ preservation, specifically the rectum intact, owing to no radical total mesorectal excision (TME), no locoregional regrowth unless amenable to limited, curative (R0) salvage surgery by local excision (LE) and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes). The secondary outcome measures encompass ypT0-1 rate, pathological complete response (pCR) rate, acute and late toxicity as per NCICTCAE V.5.0, local recurrence rate, local regional recurrence rate, disease-free survival, quality of life, and anorectal function. Clinical trial information: NCT05970900 .

Second primary squamous cell cancers in the HPV de-escalation Quarterback Trials.

e18049 Background: Patients with HPV oropharyngeal cancer (HPVOPC) have a cure rate approaching 90%, and will live for decades with the sequelae of therapy. Trials evaluating treatments for HPVOPC select patients by p16 status rather than using more accurate molecular testing; a fraction of these patients, approaching 5%, are HPV16 negative. Recurrent cancers are often not tested molecularly and may not be tested for p16. Applying molecular diagnostics for HPV at diagnosis and relapse can avoid significant mis-assignment, mistreatment, and inaccurate results in clinical trials. We reviewed and report results from the Quarterback Trials (QT) where molecular testing confirmed HPV status at diagnosis and recurrence. Methods: Patients entered on the QT were required to have &lt; 20 py smoking history, not be active smokers, have non-metastatic locally advanced disease, and have a molecularly confirmed HPV status, including genotype (PCR based DNA Sequencing). Subjects were treated with TPF chemotherapy for 3 cycles and patients with an adequate response were eligible for de-escalation of chemoradiotherapy (CRT) to 5600 cGy (RD). The first 20 patients were randomized to standard dose (SD) 7000 cGy (8) or RD (12). Patients who withdrew from the study or had an inadequate response to TPF, were treated with SD. Patients were monitored for recurrent disease by routine surveillance with physical examination and PET scan. Recurrences were confirmed with tissue biopsy. We performed a retrospective analysis of 2nd in-field primaries (SP) and compared them to local regional recurrences (LRF) in the entire eligible population. Results: 62 patients were consented on to the QTs. 2 patients failed screening and are not considered any further. 14 patients received 7000 cGy: 8/14 were randomized to SD, 5/14 had an inadequate response to TPF and 1/14 patient withdrew consent. One patient randomized to SD withdrew consent and stopped CRT at 5200cGy. There were 7 HPV+ LRF: (1 SD and 6 RD); and 4 molecularly documented in-field non-HPV SP squamous cell cancers: 2/14 SD (14%) and 2/46 RD (4%). 1 of 4 SP tumors was p16+; all were molecularly negative for HPV and had documented p53 mutations. Median time to LRF was 8 mo. (4-49) and 66 mo. (35-84) for SP. Median survival after LRF is 11 (4-72+) and after SP 18+ (3-36+). 4/11 (36%) of post treatment local regional squamous cancer events were not HPV related. Conclusions: Non-HPV SP SCC were not rare events in this documented HPV+, non-smoking population. SP were more common in the SD than the RD treated patients suggesting an RT dose dependency and causality, although other biologic explanations are possible. SP will increase and be a major cause of mortality in this population indicating a need for awareness during surveillance. p16 is inaccurate for determining HPV16 status at diagnosis and recurrence in HPV critical clinical trials and in-field cancer events should be molecularly assessed to determine if they are LRF or SP.

Analysis of ctDNA assay as a strategy for watchful waiting in locally advanced esophageal cancer.

e16126 Background: Standard treatment for locally advanced esophagogastric (EG) cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. The treatment goal is curative in order to control the tumor in the thorax, prevent regional recurrence, and to help prevent or delay metastatic progression. Despite achieving pathologic complete response (pCR) after surgery, patients with supposed local control may have recurrence up to a third of the time. Circulating tumor DNA (ctDNA) is an evolving tool in the field of oncology used as an informative biomarker. We provide longitudinal, real world observation of ctDNA minimal residual disease (MRD) to predict pCR and risk of recurrence. Methods: 22 participants with newly diagnosed locoregional EG cancer were enrolled under single institution approved protocol [IRB#1864127-7]. CtDNA-based MRD levels were obtained by Natera SignateraTM bespoke mPCR-NGS assay. Additionally, Natera Altera TM was used as a non-invasive biopsy to provide the comprehensive tumor-specific genomic profile. We evaluated thirteen participants who underwent definitive surgery and those who did not. Non-invasive plasma samples were surveilled at various timepoints which included the time of diagnosis, during neoadjuvant CRT, after definitive surgery. The primary outcome is a comparison of assay recurrence (AR) to disease recurrence (DR) defined as radiologic or clinical disease recurrence in participants with locoregional disease. Exploratory endpoints examine the profile of tumor. Results: Baseline levels were detected (n = 22) at new diagnoses. Longitudinal results demonstrated ctDNA clearance in eight participants while undergoing neoadjuvant chemoradiaton. Residual ctDNA were found in five participants for which two had clinical disease recurrence. Esophagectomy was done in three participants achieving pCR. Post procedural ctDNA were detected in one participant. Conclusions: The clearance of ctDNA favors less clinical disease recurrence in this study. This may indicate that ctDNA clearance confers lower risk of relapase. However, a larger cohort prospective study will be needed to validate the application of ctDNA as an early biomarker. The future application of ctDNA can be used to identify patients who may benefit from a watchful waiting adjuvant strategy instead of proceeding with invasive esophagectomy.

Specifics of regional recurrences in lateral tissue of the neck after surgical treatment of highly differentiated thyroid cancer

Introduction: Despite the fact that highly differentiated thyroid cancer is included in the group of malignant neoplasms with a favorable prognosis, data on the high frequency and recurrence of relapses are reported. The presence of metastatic lymph nodes in HDTC increases the risk of regional relapse by up to 27 %. According to the literature, the factors that increase the risk of recurrence are: histological type, stage, depth of extrathyroid invasion, the presence of metastatic lymph nodes, age, and the volume of primary surgical intervention. Lateral neck dissection should be performed in patients with morphologically verified metastatic thyroid cancer, but there is still no clear consensus on the volume of dissection. Aim: Assessment of factors affecting the risk of regional recurrence in the lateral neck tissue and the localization of recurrence. Materials and methods: The study included 56 patients with HDTC, in whom metastatic lateral neck nodes were identified and verified. All patients previously underwent unilateral or bilateral neck lymph node dissection in various institutions. During the period of dynamic follow-up, these patients revealed regional recurrences in the lateral tissue of the neck. The patients were observed and treated for recurrence at the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. Results: Age over 55 years is a prognostically significant factor affecting the frequency of regional relapse in the lateral neck tissue (p = 0.002). The presence of metastatic nodes in the lateral tissue of the neck at the initial treatment is a prognostically significant factor that increases the risk of regional recurrence in the lateral tissue of the neck (p = 0.017). According to the results of a single-factor analysis, a statistically significant effect of the stage on the risk of regional relapses in the lateral neck tissue was noted (p = 0.014). In 35.7 % of cases, recurrent nodes were localized in the level V. Conclusion: Main risk factors for relapse are clinico-morphological, such as age, aggressive type of HDTC, stage of the disease, N1b status after primary surgery, as well as technical defects during primary surgical treatment.

Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance.

Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood. To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC). A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of P < 0.05 was considered to indicate statistical significance. Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 0.0083). The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.