5-year DFS Research Articles

Is Programmed Death Ligand 1(PD-L1) Expression in Vulvar Cancer Prognostic for Locoregional Control?

Vulvar cancer is a rare female genital neoplasm in which surgery and radiotherapy play an integral role in the treatment paradigm; however, locoregional recurrence remains the predominant pattern of failure. Little is known about the impact of PD-L1 status in vulvar cancer and its value for clinical outcomes and response prediction to immunotherapy. We sought to explore clinical outcomes of patients with positive PD-L1 expression in vulvar cancer. Single-institution retrospective analysis of patients with surgically resectable invasive vulvar carcinoma from 2001-2021 was performed. Patients with locally advanced disease not amendable to upfront surgery or de novo metastatic disease were excluded. Immunohistochemical PD-L1 expression was assessed using the Combined Positive Score (CPS) with positive expression defined as ≥1, and Tumor Proportion Score (TPS) with positive expression defined as ≥1%. Survival and disease control outcomes were calculated using the Kaplan-Meier Method with log-rank t-test. Multivariable analysis was conducted using a parsimonious cox regression analysis using forward conditional selection. A total of 85 patients were identified with a median age of 69 years old (IQR: 59-78), 54% (n = 46) FIGO stage I-II, 97% (n = 82) squamous cell carcinoma histology, 41% (n = 35) p16 positive status, 74% (n = 63) without a history of lichen sclerosis, 40% (n = 34) without co-existing vulvar intraepithelial neoplasm (VIN), and 49% (n = 42) treated with surgery alone. There were 72% (n = 61) with positive PD-L1 TPS (≥1%), and 81% (n = 69) with positive PD-L1 CPS (≥1) expression. The median follow up was 49 months (IQR: 21-75 months). The 5-year OS was 79% (95% CI, 70%-89%), DFS 55% (95% CI, 43%-67%), local control (LC) 59% (95% CI, 47%-72%), regional control (RC) 86% (95% CI, 78%-94%), and distant metastasis (DM) 96% (95% CI, 92%-100%). PD-L1 expression was associated with lower LC and DFS by TPS ≥1%. The 5-year LC of 82% (95% CI, 65%-98%) for PD-L1 negative versus 50% (95% CI, 34%-65%) positive disease (p = 0.03). The 5-year DFS was 77% (95% CI, 59%-95%) for PD-L1 negative versus 46% (95% CI, 31%-61%) positive disease (p = 0.03). No significant DFS or LC difference was noted by CPS levels ≥1. No significant difference was observed for RC, DM, or OS. On multivariable analysis, PD-L1 TPS remained a significant predictor for LC (HR = 3.01, 95% CI, 1.07-8.95, p = 0.04). No significant difference in DFS was observed for PD-L1 TPS on multivariable analysis. PD-L1 expression is associated with higher rates of local recurrence and may represents a potentially important actionable target independent of p16 status to improve the predominant pattern of relapse in this uncommon malignancy.

Interim Analysis of a Non-Randomized Prospective Trial Comparing Hypofractionated Post-Mastectomy Radiotherapy (HF-PMRT) to Conventional Post-Mastectomy Radiotherapy (CF-PMRT) for Breast Cancer (BC) Patients

The standard of care for treatment for LABC patients who have undergone modified radical mastectomy (MRM) is PMRT. Post-mastectomy RT (PMRT) for LABC patients has been established in three trials to improve locoregional control and overall survival (OS). A published trial from China showed that HF-PMRT was non-inferior to CF-PMRT. This study was conducted to determine if HF-PMRT can provide similar efficacy and toxicity. A non-randomized prospective trial design was employed to compare HF-PMRT and CF-PMRT in post-MRM BC patients. Patients with pathologically proven BC who underwent MRM without positive margins and with less than 8 positive nodes were included. Informed consent was obtained. Patients decided which treatment they will receive. They received either HF-PMRT of 43.2 Gy in 16 fractions (fx) [2.7 Gy/fx] or CF-PMRT of 50-50.4 Gy in 1.8-2.0 Gy/fx to both chest wall and regional nodes (axillary and supraclavicular) in both regimens. Primary endpoints were 2-year OS and 2-year local recurrence free survival (LRFS). Secondary endpoints include acute and late toxicities. Analysis was done as intention-to treat. An interim analysis of 2-year results is presented. A total of 37 patients were enrolled in two separate cohorts: a single-arm cohort that recruited 10 HF-PMRT patients from 2014-2015 and a two-arm prospective trial that started recruitment last 2019 and included 12 HF-PMRT and 15 CF-PMRT patients. Median follow-up was 35 months. There were more Stage IIB and Stage III for the CF-PMRT arm [p = 0.040]. Treatment interruptions were more frequent in the CF-PMRT arm (100% vs 68%, p = 0.028). The duration of interruption was also longer in CF-PMRT (median 8 vs 3 days) [p < 0.003]. Acute and late toxicities were not statistically different. There was one patient each with RTOG Grade 2 acute skin toxicity in the HF-PMRT (4.55%) and CF-PMRT arms (6.67%) [p = 0.703]. For late toxicities, the HF-PMRT arm had 6 Grade 1 late skin toxicities and 1 Grade 3 late skin toxicity vs 1 Grade 1 late skin toxicity for CF-PMRT arm [p = 0.196]. 2-year OS rate (86.3% vs 100%, p = 0.403) 2-year DFS rate (68.18% and 73.33%, p = 0.126) were both not statistically different. There were no reported locoregional recurrences (LCR). In terms of local control, both arms have showed no LCRs. 2-year OS and DFS rate were no different. As the study has not yet reached the adequate sample size, the non-inferiority of HF-PMRT cannot be definitively concluded. Acute and late toxicities were no different. There was a significantly higher rate of treatment interruptions in the CF-PMRT compared to the HF-PMRT arm. The results of this interim analysis prove to be promising and patients will continue to be accrued. The final results of this study might have tremendous implications in local practice.

Real-World Experience of Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Anal Cancer with Long-Term Follow up and Clinical Outcomes

The standard treatment for epidermoid anal cancer (AC) is concurrent chemoradiation (CRT). Here we present real world evidence of the safety and outcomes of AC patients managed by IMRT and concurrent chemotherapy at a single academic cancer center. We retrospectively reviewed the outcomes of 180 AC patients treated with definitive CRT between 2011 and 2018. Patients were managed according to a prospectively designed protocol of IMRT with radiation dose escalated according to tumor stage: 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively, and 36 Gy for elective nodal RT. Involved nodes were given the same dose based on T category. Concurrent chemotherapy consisted of two cycles of mitomycin C (MMC, 12 mg/m2) and 5-fluorouracil (5FU, 1000 mg/m2/day x 4 days) given on week 1 and 5. There was no planned treatment break. Univariate and multivariate analysis for outcomes were performed using Cox proportional hazard method and likelihood ratio statistics. Overall survival (OS) disease free (DFS), colostomy-free survival (CFS) and local failure rates (LFR) were described by Kaplan-Meier methods. There were 128 female and 52 male patients with a median age of 64 (IQR 55-74). The median size of the primary was 4.0 cm (0.6-11.0 cm). There were 18 T1, 91 T2, 38 T3 and 33 T4 lesions; 50.6% (91/180) of the patients had N0 disease. Thirteen (7.2%) did not receive concurrent chemotherapy, and 16 (8.9%) failed to complete treatment as planned. Forty-three (23.9%) patients had a treatment gap >5 (6-33) days. Eighteen of 147 (12%) with T1-3 disease failed locally, LF was observed in 13/33 (39%) T4 lesions (P = 0.0002). The 5-year OS, DFS, CFS and LFR were 85.1%, 75.6%, 87.6% and 15.5% respectively. On multivariate analysis, increasing age and N+ disease were significant for worse OS, and increasing size of the primary tumor was the only significant factor for worse DFS, CFS and LFR. Grade ≥3 acute toxicities were observed in 42.8% of patients, with grade ≥3 neutropenia and febrile neutropenia observed in 18.9% and 13.9% of patients respectively. Six patients (3.3%) died of acute toxicities. Thirteen (7%) patients experienced grade ≥3 late toxicities. Size of the primary appears to be the most important determinant of outcome following standard CRT using IMRT for AC. Despite IMRT, almost 1 in 4 patients required a treatment break, and over 40% experienced grade ≥3 acute toxicities including neutropenia and febrile neutropenia. Future studies with RT dose escalation or de-escalation, stratifying patients based on tumor size, HPV status and molecular markers are necessary to improve outcomes and decrease treatment related toxicity.

Adjuvant Radiation Therapy Improves Local Control in the Treatment of Adnexal Carcinoma

Adnexal carcinoma (AC) is a rare subset of cutaneous malignancies derived from skin adnexa. There are limited data on the role of adjuvant radiation therapy (RT). This study investigates outcomes associated with adjuvant RT at our high-volume referral center. Using an institutional pathology database we identified 45 patients with locoregionally-confined AC treated between 2001-2020 with curative intent surgery and RT at initial diagnosis or at the time of locoregionally-confined recurrence. Clinicopathologic variables were described and time to relapse events were assessed by the Kaplan-Meier method. Median age was 64 yrs (IQR 57-71). Primary tumors were in the head and neck (H&N, n = 36, 80%), trunk/extremities (n = 8, 18%) or unknown (n = 1). The most common histologic subtypes were: sebaceous-14 (31%), microcystic adnexal carcinoma-9 (20%), eccrine-6 (13%), and trichilemmal-5 (11%). Twenty-two (50% of known primaries) had PNI. All patients had primary tumor excision. Six had clinically evident lymphadenopathy (13%), all of whom had lymph node dissection (LND). Five patients without evidence of nodal disease (13%) had sentinel lymph node biopsy (SLNB) with one having SLN+ disease. Thirty patients (67%) received adjuvant locoregional RT at initial diagnosis with the following targets: 21 (30%) primary only, 4 (13%) nodal only, and 5 (17%) both. Of those receiving nodal RT, 7 (78%) had LN+ LND with 2 of those receiving concurrent platinum-based chemoradiation. Sixteen were treated at recurrence with the following targets: 4 (25%) primary only (1 having had prior adjuvant nodal RT), 4 (25%) nodal only, and 8 (50%) both. Across the full cohort, median RT dose was 60 Gy in 30 fractions. Median follow-up from initial surgical resection was 60 months (IQR 30-160). 5-year LC, NC, DFS and DSS were 71%, 86%, 66%, and 91% respectively. The only evaluated factor associated with better outcome was adjuvant primary site RT (5-yr LC 83% vs. 56%, p = 0.01 and 5-yr DFS 83% vs. 46%, p = 0.0003). All 15 patients with local recurrence (LR) had salvage surgery with median subsequent follow-up of 75 months (IQR 2-94). Overall, 5 patients receiving adjuvant primary site RT at any time (initial or salvage) developed subsequent local recurrence (13%). Of the 8 patients who developed nodal recurrence (NR) during follow-up, 1 received adjuvant nodal RT at initial diagnosis. Six of 7 who did not receive prior RT then received adjuvant nodal RT after LND and only 1 developed subsequent NR. AC is a rare skin cancer with a primarily locoregional recurrence pattern. In our experience, adjuvant RT was associated with improved LC which, depending on the tumor location, may help prevent morbid or cosmetically-impactful salvage surgery. Patients with AC would benefit from radiation oncology referral to discuss adjuvant treatment.

Comparison of Pathologic Response and Survival Outcomes between Neoadjuvant Immunochemotherapy (nICT) and Neoadjuvant Chemoradiotherapy (nCRT) in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis

The neoadjuvant immunochemotherapy (nICT) is a novel treatment, which is likely to be safer for locally advanced, surgically resectable Esophageal squamous cell carcinoma (ESCC) that comparing with the traditional neoadjuvant therapy. However, the efficacy of nICT was controversial and the survival benefit remain unknown. This study included 313 patients with locally advanced ESCC who underwent surgery following neoadjuvant therapy at Sichuan Cancer Hospital from June 2017 and September 2021. The patients were divided into nICT group and neoadjuvant chemoradiotherapy (nCRT) group according to the neoadjuvant strategy. A 1:2 propensity score matching (PSM) was used to balance potential bias across several covariates between two groups with a caliper 0.05. Among the 146 patients after PSM, the baseline factors were comparable between two groups. Compared with the nCRT group, the nICT group shown a lower pathologic complete response(pCR) rate (11.54% vs 35.11%; P = 0.0039) and lymph nodes uninvolved rate (ypN0: 44.23% vs 62.77%; P = 0.0154), but a higher perineural invasion (32.69% vs 12.77%; P = 0.0075) and angioinvasion rate (40.38% vs 10.64%; P = 0.0001). However, the 2-year OS and DFS rates were similar between the nICT group and the nCRT group in overall study cohort, and these data were confirmed in the matched samples (2-year OS, 78.2% vs 77.2% [p = 0.95]; DFS, 56.9% vs 58.0% [p = 0.69]). Our preliminary findings indicate that, for individuals with locally advanced ESCC, nICT followed by surgery appears to be less effective in pathologic outcomes, while having a comparable survival rate to nRCT. These results imply a complicated and possibly multifaceted link between the kind of neoadjuvant therapy, the pathologic outcomes, and the final survival.

Evaluation of survival outcome and prognostic factors for oral cavity cancer treated with volumetric arc therapy.

This study aimed to evaluate the survival outcomes and identify prognostic factors for patients with oral cavity cancer (OCC) who underwent adjuvant treatment with volumetric arc therapy (VMAT) using simultaneous integrated boost (SIB). Data was collected for post-operated patients of carcinoma of oral cavity who received adjuvant VMAT with SIB between June 2018 and December 2022. The data was entered and analyzed using SPSS software version 20.0. Survival rates were estimated using Kaplan Meier method. To determine survival difference between the groups, log rank test was used. Multivariate analyses were performed with Cox proportional hazard model and p value < 0.05 was considered as significant. A total of 178 patients were included in the study. The median follow-up period was 26months (range 3-56months). The 3-year OS, DFS, and LRC rates were 78% (95% CI 77-79%), 76% (95% CI 74-77%), and 81% (95% CI 80-82%), respectively. Univariate analysis identified age ≥ 50years, lymph node involvement, extracapsular extension (ECE), and N2-N3 disease as significant adverse prognostic factors for OS, DFS, and LRC. Multivariate analysis confirmed age ≥ 50years and nodal involvement as independent predictors of worse OS, DFS, and LRC. Additionally, ECE independently affected OS and DFS. Adjuvant treatment with VMAT using SIBin patients with OCC is effective. Age and nodal involvement had significant impact on LRC, DFSand OS while ECE on DFSand OS.

Fertility-sparing approach to malignant ovarian germ cell tumors - Oncologic and obstetric outocome: A retrospective study.

To evaluate oncologic (such as disease-free and overall survival) and obstetric outcomes in patients diagnosed with malignant ovarian germ cell tumors (MOGCTs). Patients diagnosed with MOGCTs between March 2007 and February 2022 were evaluated and patients who underwent fertility sparing surgery were included in this retrospective study. The obstetric and oncologic outcomes were evaluated by collecting data up until the patient's last follow-up visit from the hospital records and patient files. The study was approved by Başkent University Institutional Review Board (KA23/124). Seventy FSS patients were included in this study. The median age of the patients was 22.5 years (range: 11-37). The median follow-up time was 92.0 months (10-189). Immature teratoma was the most common histological subtype (32.9%). Bilateral involvement was detected in only one patient with immature teratoma (1.4%). The 5-year DFS rates of immature teratoma, dysgerminoma, yolk sac, and mixed germ cell histologic types were 91.1%, 94.1%, 82.4%, and 88.9%, respectively (P: 0.716). The 5-year OS rates of the same histologic types were 95.7%, 100%, 88.2%, and 88.9%, respectively (P = 0.487). All patients (100%) had a regular menstrual cycle after the completion of adjuvant treatment. The mean time between the last chemotherapy and menstruation was 4.38 months. To date, a total of 34 patients tried to conceive after the completion of disease treatment. A total of 23 (67.6%) patients conceived, resulting in 27 live births in 22 (100%) patients. Fertility preservation should be the first treatment option in MOGCTs in young patients due to the unilateral involvement of the disease and its chemosensitive nature.

Comparative analysis of hypomethylating agents as maintenance therapy after allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia

We retrospectively analyzed the outcomes of 136 consecutive patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center. Among them, 76 cases used hypomethylating agents (decitabine, n = 40; azacitidine, n = 36) as post-transplant maintenance therapy, whereas 60 contemporaneous patients did not adopt maintenance therapy. The 3-year incidences of relapse in two groups were 16.6% and 39.2% (p = .001). The 3-year OS and DFS in maintenance group were 84.0% and 78.6%, which were remarkably improved than in control group (60.0% and 58.0%) (p = .004, p = .011). Moreover, the 3-year relapse rates for patients receiving decitabine and azacitidine therapy were 8.5% and 25.0%, respectively (p = .019). Patients utilizing decitabine had more common possibility of grade 3–4 neutropenia than azacitidine (20.0% vs. 2.8%, p = .031). These results indicate that maintenance therapies using hypomethylating agents could reduce the risk of post-transplant recurrence, resulting into remarkable superior survival. Decitabine might lower relapse after allo-HSCT with somewhat more severe myelosuppression when being compared to azacitidine.

The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on stage I non–small cell lung cancer with sensitive EGFR mutations

Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of adjuvant EGFR-TKIs with observation in such patients by incorporating an established 14-gene molecular assay for risk stratification. This retrospective cohort study was conducted at the First Affiliated Hospital of Guangzhou Medical University (Study ID: ChNCRCRD-2022-GZ01). From March 2013 to February 2019, completely resected stage I NSCLC (8th TNM staging) patients with sensitive EGFR mutation were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics. A total of 227 stage I NSCLC patients were enrolled, with 55 in EGFR-TKI group and 172 in the observation group. The median duration of follow-up was 78.4 months. After IPTW, the 5-year DFS (HR=0.30, 95% CI, 0.14-0.67; P=0.003) and OS (HR=0.26, 95% CI, 0.07-0.96; P=0.044) of the EGFR-TKI group were significantly better than the observation group. For subgroup analyses, adjuvant EGFR-TKIs were associated with favorable 5-year DFS rates in both IA (100.0% vs. 84.5%; P=0.007), and IB group (98.8% vs. 75.3%; P=0.008). The 14-gene assay was performed in 180 patients. Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant improvement in 5-year DFS rates compared to observation (96.0% vs. 70.5%; P=0.012), while no difference was found in low-risk patients (100.0% vs. 94.9%; P=0.360). Our study suggested that adjuvant EGFR-TKI might improve DFS and OS of stage IA and IB EGFR-mutated NSCLC, and the 14-gene molecular assay could help patients that would benefit the most from treatment. This work was supported by China National Science Foundation (82022048, 82373121).

Multimodal assessment after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer accurately predicts complete responders.

This study aimed to compare local regrowth rates after total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy (SNCRT) in locally advanced rectal cancer (LARC) patients that were strictly selected and assessed with a multimodal approach. Secondary outcomes were 4-year disease-free (DFS) and overall survival (OS) rates. Locally advanced rectal cancer patients without distant metastases treated at Koç Healthcare Group between January 2014 and January 2021 were included. Patients were assessed for complete response with a combination of digital rectal exam, endoscopy, and magnetic resonance imaging with a dedicated rectum protocol. The systemic evaluation was performed with an upper abdomen MRI using intravenous hepatobiliary contrast agent and a thorax CT. Of the 270 patients with LARC, 182 fulfilled the inclusion criteria. Ninety-seven (53.3%) underwent TNT, while 85 (46.7%) underwent SNCRT. A cumulative combination of pathological and sustained clinical complete response was significantly higher in the TNT group than in the SNCRT (45.4% vs. 20.0%, p < 0.0001). After a median follow-up of 48months, seven patients in the W&W group had regrowth [TNT: 4 (10.8%) vs. SNCRT: 3 (23.1%), p = 0.357]. Based on pathological examination, complete/near complete mesorectum rates (p = 1.000) and circumferential resection margin positivity rates (p = 1.000) were similar between the groups. The 4-year DFS and OS rates were comparable. The patients with clinical or pathological complete response had significantly longer overall survival (p = 0.017) regardless of the type of neoadjuvant treatment. Multimodal assessment after TNT effectively detects complete responders, resulting in low local recurrence and increased cumulative complete response rates. However, these outcomes did not translate into a survival advantage.

Humanized anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.

Chemoradiotherapy effcacy in squamous cell rectal cancer: a propensity score matched analysis

Introduction. Sporadic cases of squamous cell carcinoma of the rectum (rSCC) do not allow a comparative characterization of tumor aggressiveness and its response to chemoradiotherapy in relation to more common squamous cell entities, in particular, anal squamous cell carcinoma (aSCC). Objective: comparative evaluation of the short- and long-term results of chemoradiation therapy in patients with rSCC and aSCC. Material and Methods. In this retrospective study we included patients with nonmetastatic squamous cell carcinoma of the rectum (rSCC) and anal canal squamous cell carcinoma (aSCC) who received chemoradiotherapy and compared them in a 1:1 ratio using propensity-score matching. The dynamics of tumor response to treatment were compared by Kaplan-Meier survival analysis (OS and RFS) followed by Log-Rank verifcation, rate of complete response after 6 months. Results. A total of 15 pairs of matched patients were evaluated. Patients in both groups had reliably similar sex, age, histological grade, initial primary tumor size, differing only in tumor histological subtype. In the aSCC group, 60 % of patients had metastases to pelvic lymph nodes, while in the rSCC group metastases had 46.67 % (p=1). The median follow-up was 44 months. The 3-year OS in the aSCC group of patients was 76.9 %, and 71.4 % in the rSCC group (p=0.567). The 3-year DFS in the aSCC group was 66.7 %, and in the rSCC group 34.7 % (p=0.406). The rate of achieving complete clinical response to CRT after 6 months was 86.7 % for the aSCC group and only 46.7 % for the rSCC group (p=0.05). Organ-saving treatment was achieved in 93.3 % of aSCC patients and 73.3 % of rSCC patients (p=0.33). Conclusion. Overall and recurrence-free survival rates were not signifcantly decreased for rSCC patients relative to aSCC patients. This indicates a similar course and prognosis in the two diseases, but rSCC is characterized by a signifcantly lower rate of complete response to treatment.

Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

545 Optimal Surgical Approach for Mid-Transverse Colon Cancer; a Systematic Review and Meta-Analysis

Abstract Background and Aim The incidence of cancer colon below the age of 50 has increased dramatically. in addition, the database lacks a review to analyze the outcomes of surgeries for mid-transverse colon cancer with several recent controversial studies. Our aim was to compare the outcomes of extended hemicolectomy versus transverse colectomy for mid-transverse colon cancer. Method PubMed, Scopes, Web of Science and Cochrane library were searched for eligible studies from inception to 1 May 2022 and a systematic review and meta-analysis were done to detect Results according to eligibility criteria 8 studies (2237 patients) were included in our study. The pooled results of the included studies showed no difference in the 5-year OS, 3-year DFS and 5-year DFS between the two types of surgery (5-year OS, RR = 1.15, 95% CI = 0.94-1.39, P = 0.17), (3-year OS, RR = 0.96, 95% CI = 0.88-1.06, P = 0.42) and (5-year DFS, RR = 1.21, 95% CI = 0.91-1.62, P = 0.20). In addition to that, the recurrence rate and the incidence of complications were similar in the two groups (Recurrence rate, RR = 1.08, 95% CI = 0.62-1.89, P = 0.79) and (Complications, RR = 1.07, 95% CI = 0.74-1.54, P = 0.72). however, the number of LN harvest and the time of the operation was more in case of extended hemicolectomy. Conclusions Despite harvesting less LN, transverse colectomy has similar oncological outcomes to extended hemicolectomy for mid-transverse colon cancer. Moreover, no significant difference in the incidence of complications.

Impact of HR-HPV infection on oncological outcomes in early cervical cancer.

This study aimed to investigate the differences in long-term oncological outcomes between high-risk human papillomavirus (HR-HPV) negative and HR-HPV positive early-stage cervical cancers. We retrospectively analysed 2061 cases of early-stage cervical cancer from the Chinese cervical cancer clinical diagnosis and treatment database. Kaplan-Meier curves were used to describe the survival outcomes of different HR-HPV infections. Cox proportional hazard regression model was used to analyze and determine independent risk factors. K-M analysis revealed no significant difference in 5-year OS between HR-HPV negative and HR-HPV positive groups (OS: 95.0% vs.95.6%, P=0.900). A significant difference was observed in 5-year DFS between the HR-HPV negative and HR-HPV positive groups (DFS: 87.2% vs.91.9%, P=0.025). Cox proportional hazard regression model indicated that HR-HPV infection (negative vs. positive) was an independent factor influencing 5-year DFS after early cervical cancer surgery (DFS: hazard ratio [HR]=1.862, P=0.022). HR-HPV infection (negative vs positive) was not an independent factor influencing 5-year OS after early cervical cancer surgery (OS: P=0.813). After 1:1 PSM pairing, there was no significant difference in 5-year OS and DFS between HR-HPV negative group and HR-HPV positive group (OS: 91.6% vs.95.0%, P=0.297; DFS: 87.2% vs.85.1%, P=0.758). Cox multivariate analysis indicated that HR-HPV infection was not an independent factor influencing 5-year OS and DFS after early cervical cancer surgery (OS: P=0.806, DFS: P=0.251). The tumour results of HR-HPV negative group and HR-HPV positive group were similar, after eliminating the differences in known variables that affect the oncological outcomes of cervical cancer. The treatment plan of HR-HPV positive cervical cancer is suitable for HR-HPV negative cervical cancer.

Complete Mesocolic Excision (CME) versus Conventional RT Hemicolectomy (CRH) in Patients with Right Sided Colon Cancer: A Systematic Review and Meta-Analysis

Abstract Background We live in an era with improved worldwide average living standards and increased access to adequate healthcare that has considerably improved the diagnosis and treatment of diseases. These measures have had an impact on average life expectancy in most regions of the world. Aim of the Work The aim of this study is to perform a systematic review and meta-analysis to investigate safety and long-term out- comes of Complete Mesocolic Excision (CME) Versus Conventional RT Hemicolectomy (CRH) in patients with right sided colon cancer. Materials and Methods This study is a systematic review and meta-analysis. Literature search, study design, and data analysis were performed following PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Five medical databases were used in this research: MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science, and Embase. The keyword was as follows: ―complete mesocolic excision.‖ I select studies published up to December 2020. I select only articles written in English and we did not include abstracts or unpublished data. After literature search, 30 studies have been recorded. Screening by titles and abstracts led to the identification of 20 possibly relevant articles. Of these records, 8 studies were excluded because patients with distal transverse and/or left colon cancer were also evaluated. Moreover, in 3 studies, only the most recently record was selected. Lastly, 8 studies, published between 2010 and 2020, met inclusion criteria. All selected studies were observational; 4 of them were prospective. Overall, 1762 patients were enrolled in qualitative and quantitative analysis, 700 in the CME group and 1062 in the CRH group. Results Postoperative complications were reported in 9 studies showing that no difference was observed between techniques. Six studies separately analyzed surgical and non-surgical postoperative complications. No significant variation was reported between the 2 groups in the 2 different types of complications (surgical complications OR 1.09, 95% CI 0.72–1.63, p = 0.69, no surgical complications OR 1.37, 95% CI 0.79–2.36, p = 0.26, respectively). No significant difference was al- so observed between the two groups in terms of anastomotic leakage, while a significant negative median was reported for intraoperative bleeding in favor of CME group. 4 studies evaluated the procedure time which was significantly shorter for CRH, although heterogeneity levels among studies was high. The analysis of postoperative length of stay showed no difference between the two groups of patients. Number of lymph node yield was reported in 8 studies. The pooled analysis of 1762 patients found a positive median retrieval of 9.17 in CME group. High heterogeneity among the included studies was detected. Seven studies reported data of 3-year OS with a significant OS benefit in CME group. This data was characterized by moderate between-study heterogeneity. Furthermore, 76.4% of patients undergoing CME surgery were alive at 5 years, compared with 68.2% of CRH. Meta-analysis of 3 studies reporting 5-year DFS con- firmed the significant DFS benefit for patients undergoing CME. No significant heterogeneity was observed between the 3 studies. Conclusion My study confirm that CME with CVL associated with D3 lymphadectomy in right-side colon cancer improved not only staging but also prognosis, particularly in II and III stage; CME was a significant independent predictive factor for disease-specific survival at 3 years and 5 years compared with CRH associated with D2 lymphadectomy. CME is a safe and reproducible procedure with acceptable morbi-mortality.

SP8.5 Emergency laparoscopic and open right hemicolectomy for right colonic malignancy: A retrospective comparative single centre study

Abstract Aim Minimally invasive surgery has gained wide acceptance in general surgery and is being increasingly used to treat colon cancers. However, there are no randomized controlled trials comparing laparoscopic against open emergency colectomies. This study aims to compare the clinical and pathological outcomes for laparoscopic and open right colectomy in the emergency setting. Methods This single-centre study involved a total of 201 patients who underwent emergency laparoscopic and/or open right hemicolectomy for right colonic malignancy between 2009 and 2019. Results A total of 201 right colectomies were performed. Among these procedures, 84 were operated laparoscopically and 117 with an open midline laparotomy. In the laparoscopic group, 13 were converted to open procedures. Patient demographics were similar across both groups with regard to age, sex, BMI, ASA grade, and tumour stage. Patients in the laparoscopic group had significantly shorter hospital stays [Median = 8 vs. 13 days], higher number of lymph nodes harvested [Median = 22 vs 18]. Postoperative ileus was less common in the open group than in the laparoscopic group [9(7.7%) vs 7(8.3%), P= 1.000]. There was no significant difference in major complications, anastomotic leak, and mortality. Median 5-year DFS for the laparoscopic group was 9.9 months in comparison to 9.7 months. Median OS for the laparoscopic group was 15.6 months compared to 12.3 months in the open group. Conclusions Emergency laparoscopic right hemicolectomy seems to be safe with equivalent oncological outcomes to open surgery. Randomized control trials are required to further investigate the role of laparoscopy in emergency surgery for right colon cancers.

Relationship between STAP1 methylation in peripheral blood T cells and the clinicopathological characteristics and prognosis of patients within 5-cm diameter HCC.

The aim of this study is to explore the methylation of signal transduction adaptor protein 1 (STAP1) in peripheral blood T cells as a prognostic marker for hepatocellular carcinoma (HCC) ≤5 cm. A total of 66 HCC patients who visited our hospital from November 2012 to June 2016 were retrospectively analyzed, and 55 patients who met the inclusion and exclusion criteria were studied. Clinical and pathological data were collected from all patients to detect STAP1 methylation. STAP1 methylation expression was analyzed in HCC patients ≤5 cm with different clinicopathological features; univariate and independent prognostic factors were analyzed in HCC patients; and the relationship between STAP1 methylation expression and prognosis was analyzed in HCC patients. There was no significant difference in STAP1 methylation expression between patients with different gender, age, history of alcoholism, history of liver cirrhosis, recurrence, 3-year OS, 5-year OS, treatment, number of tumors, tumor diameter, HBV-DNA, HBSAg, Hbe-Ag expression, and AFP level (P>0.05); however, there was significant difference in STAP1 methylation expression between patients with different survival, 3-year DFS, and 5-year DFS (P<0.05). Multivariate Cox regression analysis showed that recurrence and STAP1 methylation were independent factors for OS and DFS (P<0.05). Kaplan-Meier survival curve results showed that the median survival time, OS, and DFS of STAP1 hypermethylation expression were shorter than those of hypomethylation (P<0.05). STAP1 methylation in peripheral blood T cells serves as a potential prognostic marker for HCC ≤5 cm.

Treatment of anemic syndrome in patients receiving surgical and chemotherapeutic treatment for breast and colorectal cancer

Introduction. Anemia syndrome is a common disease that reduces the quality and life expectancy of cancer patients. Prevention, timely diagnosis and effective treatment of anemia are statistically significantly associated with a favorable clinical outcome of the treatment of patients, and also contributes to better tolerability of anticancer therapy.Aim. Evaluation of the effectiveness of oral iron preparations and parenteral use of erythropoietin-alpha in patients with breast cancer and colorectal cancer, iron deficiency anemia or severe iron deficiency, immediate and long-term results of treatment, as well as the quality of life of patients with breast cancer and colorectal cancer.Materials and methods. A retrospective analysis of the material from the Blokhin National Medical Research Center of Oncology, involved 133 patients (validation group 68 people, control group – 65 people), patients with breast cancer or colorectal cancer, suffering from anemia. Depending on the form of anemia, patients were prescribed therapy – oral iron preparations with epoetin alfa in combination or in monotherapy. The effectiveness of therapy was assessed by the rate of blood hemoglobin. Analysis and statistical processing of results using IBM SPSS Statistics 26.0. Survival analysis was carried out using the KaplanMeier method. Descriptive statistics methods are used to analyze socio-demographic and traditional patients.Results. With a median follow-up of 61.2 months, the exclusion groups did not have significant differences in overall survival (p &gt; 0.05). However, the group of patients with IDA who received therapy to correct the anemic syndrome and the group with FDA without adequate therapy had a greater significance in terms of 5-year OS (93.5 and 69.6%, respectively; p = 0.02). There were also no significant values for the 5-year DFS indicator (p &gt; 0.05). However, the groups of patients with IDA who received and did not receive therapy to correct anemia probably made a big difference in terms of 5-year DFS (90.3 and 63.9%, respectively; p = 0.025). The group of patients with IDA treated with anemia to correct anemic syndrome clearly differed from the group of patients with FAD without therapy to correct anemia in terms of 5-year OS (90.3 and 43.6%, respectively; p &lt; 0.001).Conclusions. Carrying out antianemic therapy can significantly increase the 5-year relapse-free survival in patients with iron deficiency anemia (90.3 and 63.9%, with and without therapy, respectively; p = 0.025).

Odontogenic Carcinosarcoma: Clinicopathologic and Molecular Features of Three Cases, a Literature Review and Nomenclature Proposal.

Odontogenic carcinosarcoma (OCS) is a rare odontogenic malignancy with limited characterization and unexplored molecular features. We report clinicopathologic and molecular findings in 3 additional OCS and review the literature. 3 OCS (5.1%) were identified among 59 malignant odontogenic tumors (in our archives from 1992 to 2022). Clinical, radiologic, histopathologic, immunophenotypic, and molecular findings were reviewed. Data from prior case reports and systematic or non-systematic reviews were extracted for analysis. Three mandibular OCS (age range: 66 to 72 years; 1 male, 2 females) were identified. Case 1 had novel clear-cell morphology, multiple recurrences, and a lethal outcome 28 months after resection. EWSR1 rearrangements were negative, but the tumor showed focal nuclear β-catenin and strong LEF-1 immunoreactivity. Case 2 demonstrated ameloblastic and sclerosing features and encased the inferior alveolar nerve; the patient was disease-free 22 months after resection with adjuvant chemoradiation therapy. LEF-1 was again strongly positive, and next-generation sequencing demonstrated 9p region-(CDKN2A, CDKN2B) copy number loss, and 12q region-(MDM2, CDK4) copy number gain. Case 3 showed clear-cell and markedly sclerosing features; no follow-up information was available. Literature review along with the current cases yielded 20 cases. OCS showed a male predilection (1.5:1), mandibular predominance (80%, typically posterior), and a bimodal age distribution (modes: 27.7 years, 62.7 years). OCS presented as masses (100%), often with pain (55%), and paresthesia (45%). Tumors were typically radiolucent (88.9%), with bone destruction (61.1%), and/or tooth effacement (27.8%). Preoperative biopsy was sensitive for malignancy (85.7%). At least 45% show evidence for a precursor lesion. 3-year DSS and DFS were 58% and 35%, respectively. Regional and distant (usually lung) metastatic rates were 25% and 31.3%, respectively. Increased mitotic rates and presence of tumor necrosis trended toward worse DSS and DFS. OCS is a rare but aggressive malignancy, often arising from precursor tumors and may represent a terminal phenotype rather than a distinct entity. We describe novel clear-cell and sclerosing morphologies. Wnt pathway alterations appear important. Mitotic rates and necrosis may be adverse prognosticators. In keeping with nomenclature trends in other sites, OCS may be more appropriately designated as "biphasic sarcomatoid odontogenic carcinomas."