Chemotherapy And Radiotherapy Research Articles

Is staging for cardiac damage in aortic stenosis associated with MACE in cancer patients with prior radiotherapy or chemotherapy that underwent transcatheter aortic valve replacement?

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’>14; and left ventricular ejection fraction <50%); stage 2 (left atrial volume index >34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension> 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p<0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p <0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p<0.001, CT HR 4.49 CI (2.27 – 8.89) p<0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage >3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p<0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Chemotherapy combined with radiotherapy can benefit more unresectable HCC patients with portal and/or hepatic vein invasion: a retrospective analysis of the SEER database.

The purpose of this study is to evaluate the effects of chemotherapy and radiotherapy on the prognosis of unresectable HCC patients with portal and/or hepatic vein invasion. A retrospective analysis of unresectable HCC patients with portal and/or hepatic vein invasion registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. The propensity score-matching (PSM) method was used to balance differences between groups. Overall survival (OS) and cancer-specific survival (CSS) were the interesting endpoints. OS was calculated from the date of diagnosis to the date of death caused by any cause or the last follow-up. CSS was defined as the interval between the date of diagnosis and date of death due only to HCC or last follow-up. OS and CSS were analyzed by using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model. A total of 2,614 patients were included. 50.2% patients received chemotherapy or radiotherapy and 7.5% patients received both chemotherapy and radiotherapy. Compared to the untreated group, chemotherapy or radiotherapy (COR) (HR = 0.538, 95% CI 0.495-0.585, p < 0.001) and chemotherapy and radiotherapy (CAR) (HR = 0.371, 95% CI 0.316-0.436, p < 0.001) showed better OS. In the COR group, Cox analysis results showed AFP, tumor size, N stage and M stage were independent risk factor of OS. Competing-risk analysis results showed AFP, tumor size and M stage were independent risk factor of CSS. In the CAR group, AFP and M stage were independent risk factors of OS. Competing-risk analysis results showed M stage were independent risk factor of CSS. Kaplan Meier analysis showed chemotherapy combined with radiotherapy significantly improves OS (10.0 vs. 5.0 months, p < 0.001) and CSS (10.0 vs. 6.0 months, p = 0.006) than monotherapy. AFP positive and distant metastasis are the main risk factors affecting OS and CSS of unresectable HCC patients with portal and/or hepatic vein invasion. Chemotherapy combined with radiotherapy significantly improves OS and CSS of unresectable HCC patients with portal and/or hepatic vein invasion.

Whole slide imaging-based deep learning to predict the treatment response of patients with non-small cell lung cancer.

This study developed and validated a deep learning (DL) model based on whole slide imaging (WSI) for predicting the treatment response to chemotherapy and radiotherapy (CRT) among patients with non-small cell lung cancer (NSCLC). We collected the WSI of 120 nonsurgical patients with NSCLC treated with CRT from three hospitals in China. Based on the processed WSI, two DL models were established: a tissue classification model which was used to select tumor-tiles, and another model which predicted the treatment response of the patients based on the tumor-tiles (predicting the treatment response of each tile). A voting method was employed, by which the label of tiles with the greatest quantity from 1 patient would be used as the label of the patient. The tissue classification model had a great performance (accuracy in the training set/internal validation set =0.966/0.956). Based on 181,875 tumor-tiles selected by the tissue classification model, the model for predicting the treatment response demonstrated strong predictive ability (accuracy of patient-level prediction in the internal validation set/external validation set 1/external validation set 2 =0.786/0.742/0.737). A DL model was constructed based on WSI to predict the treatment response of patients with NSCLC. This model can help doctors to formulate personalized CRT plans and improve treatment outcomes.

Microvascular Flap Reconstruction for Head and Neck Cancers in Previously Operated and/or Radiated Neck: Is It Safe?

Microvascular reconstruction after oncologic resection with curative intent in recurrent or second primary cancer cases is challenging not only because of the complexity of the defect but also due to difficulty in finding suitable donor vessels in the neck that has already been subjected to surgery and subsequent adjuvant treatment. In our present study, we evaluated the success of free flaps, reexplorations, and factors associated with reexploration and with flap failures in previously operated and/or radiated neck. In this retrospective study, we analyzed patients who underwent microvascular reconstruction from January 2016 to December 2018 in patients with previous surgery and/or radiation, considered as "already treated neck" (ATN). These cases were reviewed to analyze variables that included age, sex, indication for surgery (recurrence, second primary, osteoradionecrosis, and secondary reconstruction), duration since previous surgery or radiation, free flap done, donor vessels used, the need to go to the contralateral neck or outside the neck, need for vein grafts, flap reexploration rate, flap survival rate, and hospital stay of the patients. We also tried to identify factors that predisposed for a reexploration after performing reconstruction with a free flap in ATN. Of 1522 free flaps done, 371 patients were included in the study. Flap success rate was 90.8% in ATN, which was comparable to naive neck (94%; P = 0.108). The reexploration rate in ATN (16.2%) was significantly higher (P = 0.0003) than in naive neck (9.8%). The previous treatment (neck dissection) received [P = 0.001; odds ratio, 13.7 (1.87-101.6)] was the most significant predisposing factor, and patients undergoing osteocutaneous flaps were more prone to undergo reexplorations (P = 0.05). Side of anastomosis, vessel used for anastomosis, comorbidities, and time since previous treatment did not affect the reexploration rate significantly. Microvascular reconstruction can be safely performed in ATN with good success rates, and it should not be a deterrent in whom free flap is required to achieve best functional outcome. However, it may be associated with increase in reexploration rates in the postoperative period. Patients having undergone a previous neck dissection are at more risk of undergoing this reexploration in comparison with radiotherapy (RT)/chemotherapy and radiotherapy (CTRT) alone.

Arsenic Trioxide-based Nanomedicines as a Therapeutic Combination Approach for Treating Gliomas: A Review

Glioblastoma is one of the fatal and aggressive types of brain tumors. The current standard treatment for glioblastoma multiform (GBM) is surgical resection coupled with radiotherapy and chemotherapy. Although ample research has been performed, and multiple novel pharmacological approaches have been investigated for developing effective therapeutic drugs for treating GBM, the success of extending the survival of the patient is notably low. The unique barrier limiting GBM treatment is the presence of the blood-brain barrier (BBB), and most of the chemotherapeutic drugs fail to cross it due to their high molecular weight and large size. The currently used chemo drugs for GBM have poor penetration ability to the brain and cause off-target toxicity due to a high dose for maintaining drug concentration at the tumor site. The use of nanomaterial composites for co-delivery of multiple therapeutic drugs offers several advantages by encompassing the aforementioned obstacles. In this review, the first part sheds light on the characteristics of GBM and the major challenges faced by the current pharmacological treatments. The second part emphasizes the application of nanomaterials- based nanotherapeutics to overcome the challenges associated with current GBM therapy. A closer look is given to the use of FDA approved traditional Chinese medicine arsenic trioxide (ATO) and its application as co-delivery nanoparticles (i.e., ATO-NPs) against solid tumors, especially gliomas. In short, a breakthrough in nanotechnology offers a promising platform to treat GBM; however, rigorous efforts need to be devoted in order to develop novel therapeutic drugs with higher therapeutic efficiency and limited side effects.

Cancer: A Life Threatening Peril Becoming Lifestyle Disease

Caner a dreadful disease is actually one large group of diseases which dates back to times of “Hippocrates”, The Father of Medicine, (460-370BC) who used this name for the first time to talk about non-ulcer and ulcer forming tumors. Theevidence of its presence from the very past history comes from fossilized “Egyptian Mummies” having tumors on bones. Then Galen (130-200 AD) used the term “Oncos” to explain tumors. So it's a disease involving growth of abnormal cells, their proliferation and metastasizing the other tissues and organs. Now we know that biology has a branch namedOncology to deal with the scientific study of cancer and oncogenes. It took centuries to get knowledge and use modern technologies against this malady. Now we know cancer is a group disease which has hundreds of types. 19th Century saw much advancement towards its cure. Along with surgery, radiotherapy and chemotherapy were the main methods to cure cancer patients. Day by day, scientists are looking for new methods to control and cure of this curse. Hundreds of natural medicinal compounds are being tested to use clinically for its cure in order to replace the radiotherapy andchemotherapy and lower their side effects. But humanity is still fighting against this disease as the numbers of cases throughout the world are increasing day by day. If we look on the reports p r e s e n t e d b y W H O ( W o r l d H e a l t hOrganization), Cancer is the second leading cause of deaths globally which means one person in every six deaths, dies due to cancer. In 2018, the most common types of cancers reported in men were of liver, prostate, stomach, lung andcolorectal. Whereas in females the most common forms were breast, thyroid, cervical and colorectal. Cancer has become a global disasterfamily of the patient. It imparts physical, emotional and financial crisis. Unfortunately, the condition is bitterer in under developing countries. Cancer has become a lifestyle disease these days. We are living in the world withsuperficial comfort but we are breathing with urbanizations, ozone depletion, exposure to microwave and ultraviolet radiations, hazardous chemicals etc. Moreover, It is becoming a lifestyle disease due to lack of exercise, Obesity, consumptions of drugs, tobacco and alcohols. The cases of cancers are reported more in urban areas than in rural areasmore likely due to above mentioned factors. The ratio of cancer patients is expected to raise up-to 27.5 million by 2040 globally. So the battle is never ending, Humans need to figure out the factors and cutting these from their lives in orderto live a healthy life which is a blessing indeed. which is not only crunching the cancer patient but it also has damaging effects on the whole

Seroprevalence of Toxoplasma Gondii among Cancer patient in Qena Governate

Background: Toxoplasmosis is one of the most important cosmopolitan life-threatening diseases in immune-compromised patients. It is caused by an intracellular protozoon: Toxoplasma gondii(T. gondii), this parasite can cause pneumonia, encephalitis or disseminated disease in immune-deficient patients. Objectives:This study aimed to evaluate the prevalence of toxoplasmosis in Egyptian cancer patients and to correlate the prevalence with type of malignancy and the different cancer treatment modalities. Patients and Methods: This study conducted on 100 cancer patients (21 male and 79 female) who attended the Oncology Outpatient Clinic of Qena University Hospital and diagnosed by cancer , receiving chemotherapy or both chemotherapyand radiotherapy, and their ages ranging from 20 year to 76 years from January 2019 until December2020. Results: The high incidence of Toxoplasmosis was among cancer breast patient. The mean of Ig M titre is 0.849 with minimum level is 0.15 and maximum level is 10.43. There were 70 cancer patients undergoing chemotherapy, 6 of them were positive for toxoplasmaIg M(8.7%) , but 30 of whom received chemotherapy and radiotherapy, 11 of whom were infected (36.7%) according to the IgM level. Conclusion: Patients with a positive result are at risk of reactivation of the infection, while patients with a negative result should be informed to prevent primary infection.

Gut microbiota and fatigue in rectal cancer patients: a cross-sectional pilot study.

Although microbial-mediated disturbance of intestinal mucosal homeostasis (dysbiosis) is believed to contribute to the pathogenesis of chemotherapy and radiotherapy (CRT)-related fatigue, potential differences in the gut microbial diversity and in the abundance of gut microbial taxa between fatigued and non-fatigued patients have not been adequately examined, particularly in the rectal cancer population. In this cross-sectional study, we aim to examine the differences in (a) gut microbial diversity and gut microbial abundances and (b) predicted functional pathways of the gut microbiome between rectal cancer participants with and without fatigue at the end of CRT. Rectal cancer patients (n = 50) provided stool samples for 16S rRNA gene sequencing and symptom ratings for fatigue at the end of CRT. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. Fatigued (n = 35) participants showed enriched bacterial abundances of Eubacterium, Streptococcus, Adlercreutzia, and Actinomyces, as well as enriched abundances of the microbial sucrose degradation pathway, compared to non-fatigued patients at the end of CRT (n = 15). Differentially abundant microbial taxa were identified in fatigued and non-fatigued rectal cancer participants at the end of CRT. However, the exact role of these taxa (and identification of species) in the biology of CRT-related fatigue remains to be examined.

Development and Validation of a Prognostic Nomogram for Gastric Marginal Zone Lymphoma: a Surveillance, Epidemiology and End Results-based population Study

Aim: This initial study was conducted with the aim of constructing an accurate nomogram for gastric marginal zone lymphoma patients. Methods: Data from4414patients diagnosed with gastric mucosa-associated lymphoid tissue lymphoma from 2004 to 2015 were retrieved from the Surveillance, Epidemiologyand End Resultsdatabase. Multivariate analyses were conducted for the construction of the nomogram. Results: Age, sex, race, marital status, Ann Arbor stageand radiotherapy were significantly associated with overall survival, while age, marital status, Ann Arbor stage, surgery, chemotherapyand radiotherapy were independent prognostic predictors of cause-specific survival. Stratified analysis indicated that radiotherapy alone resulted in better overall survival and cause-specific survival than chemotherapy alone. However, the present study also has several limitations; for example, patients'Helicobacterpylori infection statusand the chemotherapy regimen used were unknown. Conclusion: This study constructed and validated an accurate prognostic nomogram for gastric mucosa-associated lymphoid tissue lymphoma patients.

Recent Advances and Molecular Pathway in Salivary Adenoid Cystic Carcinoma (Review)

Background: Salivary Adenoid Cystic Carcinoma (ACC) is a malignant tumor located at oral and maxillofacial regions, and its conventional treatments are surgery, chemotherapy and radiotherapy. However, its poor survival rates and prognosis resulting from the molecular mechanisms underlying the carcinogenesis remain obscure. To date, there are insufficient reviews to summarize the genes and molecular pathways for ACC. Therefore, it is required for us to highlight the main oncogenes, tumor suppressor genes and genetic signal transduction pathways associated with ACC in this review. Materials and Methods: A literature review based on PubMed for the genetic characteristics and molecular transduction pathways for ACC was conducted. Ninety articles were selected as references using the search terms or keywords such as “genes, molecular pathways, salivary adenoid cystic carcinoma or ACC”. Results: We have briefly described histopathology, current treatments and main clinical features in ACC. Besides, we have also elaborated the associated genes and pathways in this review according to the searched articles in recent years. Conclusion: We have summarized vital genes and proteins targeting or mechanism-based on proliferation, apoptosis, invasion and metastasis. Although there are few kinds of research on ACC currently exist, we expect that better detailed genetic studies would pave the way for promising advancement in our understanding of the molecular biology and pathogenesis mechanisms underlying tumors.

CypA: A Potential Target of Tumor Radiotherapy and/or Chemotherapy.

Cyclophilin A (CypA) is a ubiquitous and highly conserved protein. CypA, the intracellular target protein for the immunosuppressant cyclosporine A (CsA), plays important cellular roles through peptidyl-prolyl cis-trans isomerase (PPIase). Increasing evidence shows that CypA is up-regulated in a variety of human cancers. In addition to being involved in the occurrence and development of multiple tumors, overexpression of CypA has also been shown to be strongly associated with malignant transformation. Surgery, chemotherapy and radiotherapy are the three main treatments for cancer. Chemotherapy and radiotherapy are often used as direct or adjuvant treatments for cancer. However, various side effects and resistance to both chemotherapy and radiotherapy bring great challenges to these two forms of treatment. According to recent reports, CypA can improve the chemosensitivity and/or radiosensitivity of cancers, possibly by affecting the expression of drug-resistant related proteins, cell cycle arrest and activation of the mitogen-activated protein kinase (MAPK) signaling pathways. In this review, we focus on the role of CypA in cancer, its impact on cancer chemotherapeutic and radiotherapy sensitivity, and the mechanism of action. It is suggested that CypA may be a novel potential therapeutic target for cancer chemotherapy and/or radiotherapy.

Adjuvant Vaginal Cuff Brachytherapy and Patterns of Failure for Early Stage Uterine Carcinosarcoma

Uterine carcinosarcoma (UCS) is a rare histologic type, for which the optimal adjuvant management has not been fully established. In this study, we evaluated treatment outcomes and patterns of failure in patients with FIGO stage I-II UCS. After IRB approval, our prospectively-maintained database for women with endometrial carcinoma was queried. Seventy-four women with early stage UCS who underwent surgical staging between August 1992 and January 2018 at our institution were identified. After surgery, patients were managed with observation, chemotherapy (CT) alone, radiotherapy (RT) alone, or both CT and RT (CRT). Wilcoxon Rank test and Chi-Squared Test of Independence were used to assess the effect of treatment modality on various clinical parameters. The Kaplan-Meier product-limit method was used to calculate the rates of relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Univariate and multivariate analyses were employed to identify significant predictors for the survival rates. Median follow-up duration was 51 months (range, 5.1-291.6 months). The median age was 67.0 years. Distribution of FIGO stages was as follows: 48 women (65%) with FIGO stage IA, 17 (23%) IB, and 9 (12%) II. After surgery, 8 (11%) patients received RT alone, 19 (26%) had CT alone, 28 (38%) were treated with CRT, and 19 (26%) were clinically observed and did not receive any adjuvant therapy. All women who had RT received it in the form of high-dose rate (HDR) vaginal cuff brachytherapy alone (median surface dose of 30 Gy in 5 fractions) using a single channel vaginal cylinder. For patients who received chemotherapy, a median of 6 cycles (range, 3-6 cycles) of carboplatin and paclitaxel were administered. As of the most recent follow-up, 25 (34%) patients experienced recurrence of disease: 3 in the vagina only, 1 in the pelvic region only, 4 in both vagina and pelvic region, 1 in paraaortic region, and 16 in distant sites. Wilcoxon Rank test and Chi-Squared Test of Independence showed that neither the rate nor location of recurrence could be predicted by the modality of adjuvant therapy (p>0.05). Five-year OS was 66%, 38%, 81%, and 35%, respectively for CT alone, RT alone, CRT, and observation, respectively (p=0.008). Five-year RFS was 67%, 73%, 76%, and 44%, respectively for CT alone, RT alone, CRT, and observation, respectively (p=0.16). Five-year DSS was 76%, 71%, 81%, and 45%, respectively for CT alone, RT alone, CRT, and observation, respectively (p=0.07). Our results suggest that adjuvant vaginal cuff brachytherapy combined with chemotherapy for women with early stage uterine carcinosarcoma is likely to produce the best survival outcome, but a larger study is needed to further confirm the benefits.

Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy

PURPOSEThe randomized Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with high-risk endometrial cancer (EC). Because The Cancer Genome Atlas defined an EC molecular classification with strong prognostic value, we investigated prognosis and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants.METHODSParaffin-embedded tissues of 423 consenting patients were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain were done to classify tumors as p53 abnormal (p53abn), POLE-ultramutated (POLEmut), MMR-deficient (MMRd), or no specific molecular profile (NSMP). The primary end point was recurrence-free survival (RFS). Kaplan-Meier method, log-rank test, and Cox model were used for analysis.RESULTSMolecular analysis was successful in 410 high-risk EC (97%), identifying the 4 subgroups: p53abn EC (n = 93; 23%), POLEmut (n = 51; 12%), MMRd (n = 137; 33%), and NSMP (n = 129; 32%). Five-year RFS was 48% for patients with p53abn EC, 98% for POLEmut EC, 72% for MMRd EC, and 74% for NSMP EC (P < .001). The 5-year RFS with CTRT versus RT for p53abn EC was 59% versus 36% (P = .019); 100% versus 97% for patients with POLEmut EC (P = .637); 68% versus 76% (P = .428) for MMRd EC; and 80% versus 68% (P = .243) for NSMP EC.CONCLUSIONMolecular classification has strong prognostic value in high-risk EC, with significantly improved RFS with adjuvant CTRT for p53abn tumors, regardless of histologic type. Patients with POLEmut EC had an excellent RFS in both trial arms. EC molecular classification should be incorporated in the risk stratification of these patients as well as in future trials to target specific subgroups of patients.

Current Developments in Targeted Drug Delivery Systems for Glioma.

Glioma is one of the most commonly observed tumours, representing about 75% of brain tumours in the adult population. Generally, glioma treatment includes surgical resection followed by radiotherapy and chemotherapy. The current chemotherapy for glioma involves the use of temozolomide, doxorubicin, monoclonal antibodies, etc. however, the clinical outcomes in patients are not satisfactory. Primarily, the blood-brain barrier hinders these drugs from reaching the target leading to the recurrence of glioma post-surgery. In addition, these drugs are not target-specific and affect the healthy cells of the body. Therefore, glioma-targeted drug delivery is essential to reduce the rate of recurrence and treat the condition with more reliable alternatives. A literature search was conducted to understand glioma pathophysiology, its current therapeutic approaches for targeted delivery using databases like Pub Med, Web of Science, Scopus, and Google Scholar, etc. Results: This review gives an insight to challenges associated with current treatments, factors influencing drug delivery in glioma, and recent advancements in targeted drug delivery. The promising results could be seen with nanotechnology-based approaches, like polymeric, lipidbased, and hybrid nanoparticles in the treatment of glioma. Biotechnological developments, such as carrier peptides and gene therapy, are future prospects in glioma therapy. Therefore, these targeted delivery systems will be beneficial in clinical practices for glioma treatment.

Probability of Survival in Patients with Gastric Cancer

Background: Gastric cancer is the most common cancer and currently, the prevalence of gastric cancer is 10 percent among all cancers in the world. There are more than 870 thousand new cases worldwide each year and it causes the death of more than 650 thousand patients. This study was performed to estimate the life table survival in patients with gastric cancer in province Qazvin of Iran at 2010-2020. Methods: This is cross – sectional study whit analytical type method which has been conducted using the process of longitudinal and survival study. The study population includes all patients diagnosed with gastric cancer in Qazvin province between the years 2010 to 2020. The samples size (600 patient) selected by the random systematic simple sample method than all the patients diagnosed with gastric cancer referred to Qazvin hospitals for treatments including surgery, radiotherapy and chemotherapy that were in the same group from the time aspect, which was recorded from 2010 until 2020. The most important factors affecting survival rate were marked and analyzed with the Kaplan-Meier and cox model. Results: 68 % of 600 patients, were male with a mean age of (48.23± 8 years), and 32% of patients were female with a mean age of (46±9) and median survival rate were 36 and 40 months, and the survival rate of 1 to 5-year of patients were 16,22,28,34,52 respectively. In cox model, factors including sex, age of diagnosis, lead-time and type of treatment have significant correlation with survival rate (p ≤0.05). Conclusion: Early diagnosis and treatment of disease in the early stages with suitable surgery increase the survival of patients. However, it does not have special effects on life length of patient but it will increase the quality of life for patients.

Autophagy and Tumour Stem Cells.

Autophagy is critical for the survival and stemness maintenance of cancer stem cells (CSCs) and is an enhancer of CSC tumorigenesis. At the same time, autophagy contributes to conditions optimal for facilitating the invasion and metastasis of CSCs. Moreover, autophagy induces the dormant state of CSCs to help them resist the cytotoxic effects of chemotherapy andradiotherapy, thereby improving the likelihood of their survival. The combination of autophagy inhibitors with specific drugs targeting specific CSC subpopulations is expected to act specifically on CSCs and produce fewer toxic side effects on normal tissues. This in-depth study is very timely and important for further identifying the potential role of autophagy in different states of CSCs and places a particular emphasis on exploring molecular mechanisms in the regulation of autophagy via advanced techniques based on molecular biology.

LBA63 - Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on adjuvant therapy

BackgroundThe PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with stage I-III endometrial cancer with high-risk features (HREC). Since the TCGA defined 4 molecular subgroups of EC with strong prognostic value, we investigated outcomes and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants. MethodsParaffin-embedded tissues of 423 consenting patients (64% of 660) were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE pathogenic exonuclease domain mutations were done to classify tumours as p53 mutant staining (p53abn), POLE ultramutated (POLEmut), MMR deficient (MMRd), or no specific molecular profile (NSMP). The Kaplan-Meier method, log-rank test and Cox model were used for analysis. ResultsMolecular analysis was successful in 410 HREC (97%), identifying the four subgroups; p53abn (n=92, 22%), POLEmut (n=52, 13%), MMRd (n=137, 33%) and NSMP (n=129, 32%). Five-year recurrence free survival (RFS) was 50% for patients with p53abn HREC, 98% for POLEmut, 74% for MMRd and 76% for NSMP (p<0.0001). Patients with p53abn HREC significantly benefited from combined chemotherapy and radiotherapy (5-year RFS with CTRT 61% versus 37% for RT, log-rank p=0.015, Table 1). In contrast, POLEmut-HREC had 97-100% survival in both trial arms, and 5-year RFS for MMRd-HREC was 72 vs 76% for CTRT vs RT.Table: LBA63Recurrence-free survival by molecular subgroupTable: LBA63Events5-year estimate %HR (95% CI)P value of HRp53abn ECRT2837,21CTRT2061,10,50 (0,28-0,88)0,017POLEmut ECRT196,61CTRT01000,02 (<0,01->104)0,632MMRd ECRT1775,81CTRT1872,41,15 (0,59-2,22)0,687NSMP ECRT1968,91CTRT1781,20,71 (0,37-1,37)0,311 ConclusionsMolecular EC classification has a strong prognostic value in HREC and better identifies those who benefit from adjuvant CTRT than clinicopathological factors. Patients with p53abn HREC had significantly improved RFS with adjuvant CTRT, while those with MMRd did not seem to benefit from chemotherapy. Patients with POLEmut HREC had an excellent RFS in both arms. Future trials should incorporate the molecular classification and target specific subgroups. Clinical trial identificationNCT00411138. Legal entity responsible for the studyLeiden University Medical Center. FundingKoningin Wilhelmina Fonds voor de Nederlandse Kankerbestrijding (KWF). DisclosureA. Leary: Travel / Accommodation / Expenses, Officer / Board of Directors: AZ; Officer / Board of Directors: Tesaro; Officer / Board of Directors: Clovis; Officer / Board of Directors: MSD; Officer / Board of Directors: Grisdstone; Officer / Board of Directors: Seattle Genetics; Officer / Board of Directors: Gamamabs; Officer / Board of Directors: Biocad; Travel / Accommodation / Expenses: Roche . H.W. Nijman: Leadership role, Founder: SME Vicinivax; Advisory / Consultancy: Aduro; Advisory / Consultancy: TRON ; Advisory / Consultancy: Merck. All other authors have declared no conflicts of interest.

Is there any benefit in adding postoperative adjuvant concurrent radiotherapy and chemotherapy for penile cancer with regional lymph node metastasis?

The aim of this study was to evaluate whether there is any benefit in adding postoperative adjuvant concurrent radiotherapy and chemotherapy (RT-CHT) for penile cancer with regional lymph node metastasis (RLNM). A single institution, retrospective study was conducted for a total of 23 patients with RLNM from penile squamous cell carcinoma. All underwent a definitive surgical intervention for both primary tumor and RLNM. Of these, 11 patients received adjuvant concurrent RT and CHT within 3 months after surgery (RT-CHT group), while 12 patients received no additional treatment (Surveillance Group). Overall survival was calculated with the Kaplan-Meier method. The difference in survival between the two groups was tested using the log-rank test. A potential prognostic factor for survival was evaluated using a univariate Cox-proportional hazards model. Median follow-up for the entire group was 15.8 months (17.1 months for the RT-CHT group and 10.7 months for the Surveillance Group). Overall survival at 1 and 2 years were 54.5% and 27.2%, respectively, for the RT-CHT Group, compared to 57.1% and 28.4% for the Surveillance Group (log-rank=0.68). On a univariate analysis, the number of involved lymph nodes and the presence of pN3 disease were associated with poor prognosis (P>0.001 and P=0.049, respectively). The RT-CHT Group had more extensive RLNM with a higher median number of positive nodes (5 vs. 3) and more pN3 disease (72.7% vs. 16.7%) than the Surveillance Group. The rate of complications requiring hospitalization was higher in the RT-CHT Group (63.6% vs. 16.6%; P=0.02), as was the rate of systemic complications (34.7% vs. 0%; P<0.01). Penile cancer with extensive RLNM carries a poor prognosis. Despite having more extensive RLNM, the RT-CHT group had a similar overall survival as the Surveillance Group. This suggests a potential benefit of postoperative adjuvant concurrent RT-CHT for patients with extensive RLNM, although it carries an increased risk of complications. Further study is warranted to assess the benefit-to-risk ratio of this combined adjuvant therapy.

Early stage anal margin cancer: towards evidence-based management.

Anal squamous cell carcinoma is an uncommon Human Papilloma Virus (HPV)‐related malignancy, the incidence of which has increased two‐ to four‐fold over the past three decades. Results from the first three phase III trials, performed in the 1990s (the largest being the ACT I trial in the UK), established concurrent mitomycin C (MMC), 5‐fluorouracil chemotherapy and radiotherapy (CRT) as the main primary treatment. Three subsequent trials (including ACT II in the UK, performed between 1998 and 2008, demonstrated evidence of no benefit from the use of additional chemotherapy before or after CRT, or concurrent cisplatin.

The Utility of Dissected Lymph Node Number and Lymph Node Metastasis Ratio In Stage IIIC Endometrium Adenocarcinoma: A Multicentric Analysis

The prognostic impact of number of dissected and metastatic lymph nodes, the lymph node metastasis ratio in stage IIIC endometrium cancer is not well-studied. Thus, the purpose of this retrospective multicentric study is to investigate the prognostic value of the number of dissected (LNC) and positive nodes (pN) with the value of the lymph node ratio (LNR) in FIGO stage IIIC endometrial cancer patient who received postoperative radiotherapy with or without chemotherapy. From January 2001 to December 2016, a total of 180 stage IIIC endometrial cancer patients who were treated with surgery and adjuvant postoperative radiotherapy (RT) (51 patients, 28%) or radiotherapy and chemotherapy (RT-CT) (129 patients, 72%) were retrospective analyzed. The LNR was defined as the number of positive lymph nodes divided by the total number of lymph nodes dissected. The endpoints were overall survival (OS) and progression-free survival (PFS). The median age and follow up times for entire cohort were 60 years (range 36 – 88 years) and 50.5 months (range 2.8 – 199.2 months), respectively. The median dissected and metastatic lymph node numbers were 36 (range 5 – 34) and 2 (range 1 – 45), respectively. The receiver-operating characteristic (ROC) analysis identified 36 [AUC=0.390 (%95CI; 0.304-0.476); p=002] as cut-off value for LNC, with 53% sensitivity and 53% specificity. For LNR, the cut-off value determined in ROC analysis was 10% [AUC=0.636 (%95CI; 0.548 – 0.725), p=0.001] with 60% sensitivity and 60% specificity. In univariate analysis, patients with an LNC ≥36 and LNR value less than 10% had better 5-year OS (68% vs 54% p=0.04; %76.0% vs.45.0%, p < 0.001 respectively), 5-year PFS rates (67% vs 48% p=0.01; 74% vs. 41%, p<0.001 respectively). Multivariate analysis only revealed that LNR was an independent prognostic factor for OS (hazard ratio [HR=2.06 (95% CI; 1.26-3.36); p=0.004) and PFS [HR=1.83 (95%CI; 1.16-2.88; p = 0.001)]. Additional analyses revealed grade I-II histology, receiving adjuvant chemotherapy showed better OS and PFS than counterpart groups (p=0.02, p<0.001 and p=0.04 and p<0.001 respectively). More than 10% LNR and high grade (grade III) histology are an important prognostic factors for OS and PFS in stage IIIC endometrial carcinoma patients. Our findings suggest that addition of chemotherapy to RT should be the preferred adjuvant treatment strategy for patients with stage IIIC endometrial cancer with higher grade disease and high lymph node metastasis ratio.