Postoperative Chemoradiotherapy Research Articles

The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma

ObjectiveIn advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC.MethodsIn this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT.ResultsOverall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 – 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 – 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 – 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 – 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 – 4.27, p = 0.03) were significant risk predictors.ConclusionDelays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.

The relationship between splenic dose and radiation-induced lymphopenia.

Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.

Number of positive lymph nodes and lymph node ratio predict recurrence and survival in hypopharyngeal cancer based on SEER database and validation of real-world data.

This study investigated the impacts of the number of positive lymph nodes (NPLN) and lymph node ratio (LN ratio) for patients with hypopharyngeal squamous cell carcinoma (HPSCC) based on SEER database, which were validated in the real-world data of China. A total of 520 patients from SEER database were analyzed. Then 195 patients with pathologically stage III or IV HPSCC in our center were retrospectively studied. In the SEER database, NPLN ≥ 3 was found in 36.9% of patients. Multivariate analysis revealed that LN ratio ≥ 0.138 was significant with poorer overall survival (OS) (hazard ratio [HR] = 1.525, p = 0.001) and cancer-specific survival (CSS) (HR = 1.697, p < 0.001), so was the NPLN ≥ 3 (HR = 1.388, p = 0.013; HR = 1.479, p = 0.008). Patients with NPLN ≥ 3 were found in 103 (52.8%) in our center. Multivariate analysis confirmed a significant association regarding OS (p = 0.005) or CSS (p = 0.003) between patients with LN ratio ≥ 0.138 or not. In addition, disease recurrence rate differed significantly between the patients with NPLN ≥ 3 (27.2%) and NPLN < 3 (14.1%, p = 0.026). Moreover, postoperative chemoradiotherapy (CCRT) was significantly associated with better prognosis in patients with NPLN ≥ 3. In the SEER database, NPLN ≥ 3 and LN ratio ≥ 0.138 were independent poor prognostic factors for patients with HPSCC. Whereas identifying worldwide cut-off values for LN ratio is difficult and surgeon-dependent. In our cohort, adjuvant CCRT was beneficial for OS in patients with NPLN ≥ 3.

Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer

Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. ClinicalTrials.gov Identifier: NCT03239613.

A approach of gastric conduit via the anterior of pulmonary hilum route during minimally invasive McKeown esophagectomy

BackgroundThe gastric conduit is the most commonly used replacement organ for reconstruction after minimally invasive McKeown esophagectomy. Although the optimal route of gastric conduit remains controversial, the posterior mediastinal route is physiologically preferable but is not without disadvantages. Here, we report the safety and efficacy of a method of gastric conduit reconstruction via the anterior of the pulmonary hilum route.MethodsWe have used the anterior of the pulmonary hilum route since 2021. This procedure involves pulling the gastric conduit up through a substernal tunnel between the right thoracic cavity and the abdominal cavity and passing it into the neck via the anterior of the pulmonary hilum route. In this retrospective study, we compared the clinical outcomes between 20 patients who underwent this procedure and 20 patients who underwent the posterior mediastinal route from 2021 to 2022.ResultsNo mortality was reported in either group. No significant differences were observed between the two groups in duration of surgery, blood loss, incidence of postoperative complications, and postoperative hospital stay. As a result of the anterior of the pulmonary hilum route, the primary tumor bed and lymph node drainage area were effectively bypassed, which facilitates postoperative adjuvant radiotherapy or chemoradiotherapy. The distance of the gastric conduit accompanying the airway was significantly shorter in the anterior of the pulmonary hilum route group.ConclusionsOur method is considered to be a safe and useful technique for the reconstruction of gastric conduit.

The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma

BackgroundPostoperative radiotherapy (PORT) and concurrent chemoradiation (CCRT) are indicated for patients with advanced oral cancer. However, the benefits for pT1-2N1 disease without adverse pathological features are controversial. MethodsThis retrospective study using the Taiwan Cancer Registry database included patients with pT1-2N1 oral cancer from January 1, 2011, to December 31, 2017. Overall survival was analyzed in patients receiving surgery alone, PORT, or CCRT. ResultsAmong the 862 patients, the five-year overall survival rate in patients receiving surgery alone, PORT, and CCRT was 62.2%, 58.7%, and 71.1% (P = 0.03), respectively. CCRT was associated with longer survival than PORT (P = 0.008). Survival in patients with pT2 disease was significantly higher with CCRT than PORT (P = 0.001), but no difference was observed in pT1 disease. ConclusionCCRT demonstrated a favorable impact on survival outcomes in patients diagnosed with pT2N1 oral cancer when compared to PORT. However, no significant survival benefits were observed for patients with pT1 disease.

Squamous cell carcinoma of mandibular gingiva producing both parathyroid hormone-related protein and granulocyte colony-stimulating factor: a case report.

We describe a case of mandibular gingival carcinoma with hypercalcaemia and leukocytosis caused by tumour-derived parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF). A 54-year-old man presented to our Department of Oral and Maxillofacial Surgery with a chief complaint of a left-sided mandibular gingival ulcer. A 42mm × 20mm sized ulcer was found on the left lower molar gingiva. Squamous cell carcinoma was pathologically diagnosed. The patient underwent a hemimandibulectomy, left-sided radical neck dissection, plate reconstruction, pectoralis major musculocutaneous flap reconstruction, and tracheostomy under general anaesthesia. Pathologically, two metastatic lymph nodes were identified. Residual tumour was suspected at the resection margins. Eight weeks after surgery, the patient started postoperative concurrent chemoradiotherapy (CCRT). Two weeks after CCRT, the patient developed hypercalcaemia. Serum levels of PTHrP and G-CSF increased in parallel with the progression of hypercalcaemia and leukocytosis. Immunohistochemical analysis of the surgical specimen showed positivity for G-CSF. Based on these clinical and pathological findings, the patient was diagnosed with hypercalcaemia and leukocytosis associated with malignancy and was treated with denosumab. Irradiation was terminated at 50Gy because CT showed rapid disease progression. Chemotherapy was initiated, however, four weeks after the start of chemotherapy, a CT scan showed increased metastases and pleural dissemination. Therefore, chemotherapy was discontinued. One week after the chemotherapy was discontinued, the patient died of respiratory failure.

Impact of remoteness and rurality on the treatment and survival of patients with glioblastoma in the north of Scotland

BackgroundThe geographical catchment area served by the Neurosurgical Unit in Aberdeen, Scotland is the largest in the United Kingdom. We examined whether a distance-decay effect on survival exists for patients diagnosed with glioblastoma, who have to travel substantial distances for neurosurgical and oncological treatment in the north of Scotland. MethodsElectronic medical records of adult patients with glioblastoma, referred for treatment between 2007 and 2018, who underwent surgical resection were reviewed. Travel time by car (as a measure of distance travelled) was calculated from the patients’ home to their general practice (GP) and to their main neuro-oncological centre. ResultsThere were 122 patients; 71 (58.2%) were male and the mean age was 57.8 years. The urban-rural split was 61.5% and 38.5%, respectively. Median driving time to the neuro-oncological centre was 36 min and to the GP this was 6 min. Most patients underwent either sub-total (49.6%) or gross total (46.3%) surgical resection. Post-operative treatments included: radiotherapy only (15.6%), chemotherapy only (6.6%), and chemotherapy with radiotherapy (63.1%). Temozolomide was used in 70.5% of patients. Seventeen patients did not receive any post-operative chemo-radiotherapy. The median survival time was 345 days. There was no statistically significant association between distance travelled and survival time in days. MGMT methylation status, extent of resection, Charlson co-morbidity index and treatment received significantly affected survival. ConclusionsThere was no evidence of disadvantage on survival time for patients living further from their neuro-oncological centre compared to those who live nearer.

Survival Outcomes of Temporal Bone Squamous Cell Carcinoma: A Systematic Review and Meta‐Analysis

AbstractObjectiveTemporal bone squamous cell carcinoma (TBSCC) is a rare malignancy with poor prognosis, and optimal treatment for advanced cases is uncertain. Our systematic literature review aimed to assess 5‐year survival outcomes for advanced TBSCC across different treatment modalities.Data SourcesEMBASE, Medline, PubMed, and Web of Science.Review MethodsA systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for articles published between January 1989 and June 2023.ResultsThe review yielded 1229 citations of which 31 provided 5‐year survival data for TBSCC. The final analysis included 1289 patients. T classification data was available for 1269 patients and overall stage for 1033 patients. Data for 5‐year overall survival (OS) was 59.6%. Five‐year OS was 81.9% for T1/2 and 47.5% for T3/4 (P &lt; .0001). OS for T1/T2 cancers did not significantly differ between surgery and radiation (100% vs 81.3%, P  = .103). For advanced‐stage disease (T3/T4), there was no statistical difference in OS when comparing surgery with postoperative chemoradiotherapy (CRT) (OS 50.0%) versus surgery with postoperative radiotherapy (XRT) (OS 53.3%) versus definitive CRT (OS 58.1%, P  = .767‐1.000). There was not enough data to assess the role of neoadjuvant CRT.ConclusionMost patients will present with advanced‐stage disease, and nodal metastasis is seen in nearly 22% of patients. This study confirms the prognostic correlation of the current T classification system. Our results suggest that OS did not differ significantly between surgery and XRT for early stage disease, and combined treatment modalities yield similar 5‐year OS for advanced cancers.

A Study of the Prognostic Factors for Late Cervical Lymph Node Metastasis and Distant Metastasis in Patients with cT1-2N0 Tongue Cancer.

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor-stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers.

Radiochemotherapy and interstitial brachytherapy for cervical cancer: clinical results and patient-reported outcome measures.

To evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment. Between 2003 and 2023, atotal of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients' self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires. Five-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. Asignificant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB-IIIA: 79% vs. IIIB-IVA: 33%, p = 0.015), for overall treatment time (OTT; 50-65d: 64% vs. > 65d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. > 73 Gy: 38%, p = 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with asignificant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded. In patients with advanced cervical cancer, acombination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity.

Ferroptosis in head and neck squamous cell carcinoma: from pathogenesis to treatment.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide, with high morbidity and mortality. Surgery and postoperative chemoradiotherapy have largely reduced the recurrence and fatality rates for most HNSCCs. Nonetheless, these therapeutic approaches result in poor prognoses owing to severe adverse reactions and the development of drug resistance. Ferroptosis is a kind of programmed cell death which is non-apoptotic. Ferroptosis of tumor cells can inhibit tumor development. Ferroptosis involves various biomolecules and signaling pathways, whose expressions can be adjusted to modulate the sensitivity of cells to ferroptosis. As a tool in the fight against cancer, the activation of ferroptosis is a treatment that has received much attention in recent years. Therefore, understanding the molecular mechanism of ferroptosis in HNSCC is an essential strategy with therapeutic potential. The most important thing to treat HNSCC is to choose the appropriate treatment method. In this review, we discuss the molecular and defense mechanisms of ferroptosis, analyze the role and mechanism of ferroptosis in the inhibition and immunity against HNSCC, and explore the therapeutic strategy for inducing ferroptosis in HNSCC including drug therapy, radiation therapy, immunotherapy, nanotherapy and comprehensive treatment. We find ferroptosis provides a new target for HNSCC treatment.

Histopathology images-based deep learning prediction of prognosis and therapeutic response in small cell lung cancer

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer characterized by rapid tumor growth and early metastasis. Accurate prediction of prognosis and therapeutic response is crucial for optimizing treatment strategies and improving patient outcomes. In this study, we conducted a deep-learning analysis of Hematoxylin and Eosin (H&E) stained histopathological images using contrastive clustering and identified 50 intricate histomorphological phenotype clusters (HPCs) as pathomic features. We identified two of 50 HPCs with significant prognostic value and then integrated them into a pathomics signature (PathoSig) using the Cox regression model. PathoSig showed significant risk stratification for overall survival and disease-free survival and successfully identified patients who may benefit from postoperative or preoperative chemoradiotherapy. The predictive power of PathoSig was validated in independent multicenter cohorts. Furthermore, PathoSig can provide comprehensive prognostic information beyond the current TNM staging system and molecular subtyping. Overall, our study highlights the significant potential of utilizing histopathology images-based deep learning in improving prognostic predictions and evaluating therapeutic response in SCLC. PathoSig represents an effective tool that aids clinicians in making informed decisions and selecting personalized treatment strategies for SCLC patients.

Abstract C070: Management of resectable pancreatic adenocarcinoma: Results from a data-driven approach across University of California system

Abstract Introduction Practice guidelines for resection of surgical candidates in pancreatic adenocarcinoma are consensus-driven to ensure patients receive standardized care, but current evidence regarding peri-operative strategies regarding systemic and chemoradiation treatment is based on retrospective and metanalysis, which may lead to wide variation in implementation. Methods We used a database containing deidentified data patients with pancreatic adenocarcinoma who received surgical resections across five California academic medical centers to assess peri-operative outcomes and treatment strategies. We identified length of post-operative stay, rates of post-surgical hospital readmissions, pre-operative CA19-9 values, rates, type, duration and amount of neo-adjuvant, adjuvant, and chemoradiation therapy using structured data from EMR records at these sites. ANOVA, t-test and fisher exact tests were used to determine statistical significance of differences across institutions. Cox regression models were used to determine significance in survival differences between populations. Results. We identified 2,564 patients with PDAC diagnosis who had a surgical resection of the pancreas across five University of California sites. 1948 received pancreaticoduodenectomy, 549 received distal pancreatectomies, and 67 received total pancreatectomies. Median LOS was 8.0 days, with 7-day, 30-day, and 90-day readmission rates of 7.6, 17.7 and 23.2% respectively. There were significant differences in these rates across the five medical centers, though no association with site volume. Rate of completion of 6 months of peri-operative 5-FU based systemic therapy was 62% across all sites, but only 47% for 12 cycles of FOLFIRINOX. Patients receiving at least some NAC therapy more likely to complete the recommend six months than those who did not get any systemic therapy prior to surgical resection (77.8% vs 49.3%, p-value&amp;lt;0.001, Logistic regression with Wald test for significance). There were significant differences in the timing of peri-operative therapy across the sites, as well as the frequency of using pre- and post-operative chemo-radiation. Pre-operatively CA19-9, as well as use of perioperative Gemcitabine/Abraxane or FOLFIRINOX over Gemcitabine monotherapy were significant predictors of overall survival. Conclusion Post-operative length of stay and readmission rates were significantly different across these institutions, suggesting differential efficacy in supportive care strategies. Similarly, there is significant variation of peri-operative systemic therapy strategies. Patients receiving neoadjuvant systemic therapy are significantly more likely to complete the guideline recommended six months of treatment. Rates of peri-operative chemoradiation were significantly different across medical centers, without corresponding difference in overall survival. By comparing practice differences across institutions, we may better understand how these differences affect efficacy. Citation Format: Travis Zack, Amir Ashraf-Ganjouei, Kurt Giles, Mohammed Adam, Julian Hong, Margaret Tempero, Eric Collisson. Management of resectable pancreatic adenocarcinoma: Results from a data-driven approach across University of California system [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C070.

Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review.

Dedifferentiation is a very rare phenomenon in uterine leiomyosarcoma (LMS). The aim of this study was to comprehensively analyze the clinicopathological characteristics of uterine dedifferentiated LMS (DDLMS). We reviewed electronic medical records and pathology slides from five patients with uterine DDLMS and performed immunostaining. The mean age of the patients was 56 years. Two patients presented with abdominal discomfort, while in three cases the uterine tumors were detected on routine medical examination. The mean size of the tumors was 17.0 cm. Four patients underwent hysterectomy. The initial stages were distributed as IB (2/5), IIIC (2/5), and IVC (1/5). Post-operative concurrent chemoradiation therapy, radiation therapy, and chemotherapy were administered in one, one, and two patients, respectively. Despite post-operative treatment, three patients developed metastatic recurrences in the abdominal and pelvic organs. Recurrence-free survival time ranged between 4 and 30 months. Histologically, the differentiated areas demonstrated the classic morphology of malignant smooth muscle differentiation, whereas the dedifferentiated areas resembled undifferentiated pleomorphic sarcoma and were characterized by large pleomorphic tumor cells admixed with haphazardly arranged atypical cells with marked nuclear pleomorphism. All cases also exhibited heterologous components, including chondrosarcoma (CSA; 3/5) and rhabdomyosarcoma (2/5). In two cases, the heterologous components were initially detected in primary tumors. In three cases, the primary tumors did not exhibit any dedifferentiated or heterologous components. Instead, more than half of the recurrent tumors consisted of heterologous components. Three cases showed a sharp demarcation between the LMS and CSA components, while in two cases the dedifferentiated area imperceptibly merged with the differentiated component. Immunostaining revealed that the dedifferentiated components exhibited a lack of desmin immunoreactivity in three of the four examined cases. A subset of uterine LMS represents various amounts and types of dedifferentiation and heterologous components in both primary and recurrent tumors. Routine recognition of DDLMS and distinction from its mimickers are required for accurate diagnosis and further characterization of these rare tumors.

Primary pulmonary adenoid cystic carcinoma: A clinicopathological study of 64 patients.

This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. Immunohistochemical staining showed that the tumors expressed CK7, S-100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.

A Case of Adenocarcinoma of the External Nose

Adenocarcinoma occurs very rarely in the paranasal sinuses; moreover, adenocarcinoma diagnosed in the external nose is rarely reported. A 58-year-old male patient visited our hospital with an enlarged right nasal mass. On image studies, a 1.5 cm sized mass was found on the right nasolabial fold, which was surgically removed via sublabial approach. Intraoperative frozen section examination showed inflammatory tissue without tumor cells. However, adenocarcinoma showing infiltration between the skeletal muscle layers was diagnosed on the final histopathologic examination after surgery. In the immunohistochemical staining test, CK7 positive, CK20 negative, and GCDFP-15 positive were confirmed, so metastasis of adenocarcinoma was considered first rather than primary cancer of the nasolabial fold. There was no recurrence and no tumor development in other sites after postoperative chemoradiation therapy of 32 months.

The value of subcutaneous xenografts for individualised radiotherapy in HNSCC: Robust gene signature correlates with radiotherapy outcome in patients and xenografts

PurposeTo assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets. Materials and methodsMice bearing xenografts (n = 59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n = 242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included. All patients received postoperative radiochemotherapy (PORT-C). Gene expression analysis was conducted using GeneChip Human Transcriptome Arrays. Xenografts were stratified based on their molecular subtypes and previously established gene classifiers. The dose to control 50 % of tumours (TCD50) was compared between these groups. Using differential gene expression analyses combining xenograft and patient data, a gene signature was developed to define risk groups for the primary endpoint loco-regional control (LRC). ResultsTumours of mesenchymal subtype were characterized by a higher TCD50 (xenografts, p < 0.001) and lower LRC (patients, p < 0.001) compared to the other subtypes. Similar to previously published patient data, hypoxia- and radioresistance-related gene signatures were associated with high TCD50 values. A 2-gene signature (FN1, SERPINE1) was developed that was prognostic for TCD50 (xenografts, p < 0.001) and for patient outcome in independent validation (LRC: p = 0.007). ConclusionGenetic prognosticators of outcome for patients after PORT-C and subcutaneous xenografts after primary clinically relevant irradiation show similarity. The identified robust 2-gene signature may help to guide patient stratification, after prospective validation. Thus, xenografts remain a valuable resource for translational research towards the development of individualized radiotherapy.

10204-NQPC-7 EFFECTIVENESS AND PROBLEM OF CONVALESCENT REHABILITATION FOR INDEPENDENT LIVING IN THEIR HOUSE OF PATIENTS WITH BRAIN TUMOR

Abstract OBJECTIVE The goal of brain tumor (BT) treatment is to achieve independent living (IL) in the house that KPS (Karnofsky Performance Status) is 70. However, 30% of KPS after postoperative concomitant chemoradiotherapy is between 30 to 60. Therefore, it is necessary to achieve IL in these patients. We report effectiveness for improvement of KPS, achievement of IL, and influence for health-related quality of life (HR-QoL) of convalescent rehabilitation. METHODS 138 patients with BT (average of age: 63, male/female: 76/62) who admitted in our hospital in purpose of rehabilitation, whose KPS were from 40 to 60 were enrolled from 2017. The rate of improvement (RoI) that KPS upgrade by one degree and the rate of IL (RoIL) were evaluated, and the factors to influence them were analyzed. Additionally, HR-QoL using QLQ-C30 and BN-20 on admission and discharge was evaluated. RESULTS While rehabilitation for KPS 50 achieved 70% of RoI and 60% of RoIL, that with KPS40 or less resulted in 40% of RoI and 18% of RoIL. Primary GBM 47cases with KPS60 achieved 83% of RoI and RoIL, and with KPS40 also achieved 27% of RoI and 17% of RoIL. Multivariate analysis revealed that MMSE≥24 contributed to RoI, and MMSE≥24 and KPS≥50 to the RoIL with statistically significance. HR-QoL survey revealed that financial and future uncertainty in patients with BT were higher than that in stroke, QoL scales tended to deteriorate during the hospital, and this tendency was particularly strong in patients with malignancy. CONCLUSIONS Our data revealed that rehabilitation in in patients with BT for KPS 60 or less was significantly effective to achieve IL. On the other hand, it is the issue to improve ADL in patients with KPS40 or less by effective rehabilitation and to approach the improvement of mental health.

Association of genes in hereditary metabolic diseases with diagnosis, prognosis, and treatment outcomes in gastric cancer.

Aberrant metabolism is a major hallmark of cancers and hereditary diseases. Genes associated with inborn metabolic errors may also play roles in cancer development. This study evaluated the overall impact of these genes on gastric cancer (GC). In total, 162 genes involved in 203 hereditary metabolic diseases were identified in the Human Phenotype Ontology database. Clinical and multi-omic data were acquired from the GC cohort of the Affiliated Hospital of Jiangsu University and other published cohorts. A 4-gene and 32-gene signature was established for diagnosis and prognosis or therapeutic prediction, respectively, and corresponding abnormal metabolism scores (AMscores) were calculated. The diagnostic AMscore showed high sensitivity (0.88-1.00) and specificity (0.89-1.00) to distinguish between GC and paired normal tissues, with area under the receiver operating characteristic curve (AUC) ranging from 0.911 to 1.000 in four GC cohorts. The prognostic or predictive AMscore was an independent predictor of overall survival (OS) in five GC cohorts and a predictor of the OS and disease-free survival benefit of postoperative chemotherapy or chemoradiotherapy in one GC cohort with such data. The AMscore adversely impacts immune biomarkers, including tumor mutation burden, tumor neoantigen burden, microsatellite instability, programmed death-ligand 1 protein expression, tumor microenvironment score, T cell receptor clonality, and immune cell infiltration detected by multiplex immunofluorescence staining. The AUC of the AMscore for predicting immunotherapy response ranging from 0.780 to 0.964 in four cohorts involving GC, urothelial cancer, melanoma, and lung cancer. The objective response rates in the low and high AMscore subgroups were 78.6% and 3.2%, 40.4% and 7%, 52.6% and 0%, and 72.7% and 0%, respectively (all p<0.001). In cohorts with survival data, a high AMscore was hazardous for OS or progression-free survival, with hazard ratios ranged from 5.79 to 108.59 (all p<0.001). Importantly, the AMscore significantly improved the prediction of current immune biomarkers for both response and survival, thus redefining the advantaged and disadvantaged immunotherapy populations. Signatures based on genes associated with hereditary metabolic diseases and their corresponding scores could be used to guide the diagnosis and treatment of GC. Therefore, further validation is required.