Search

Adjuvant therapy is essential in cancer treatment to enhance primary treatment effectiveness, reduce adverse effects, and prevent recurrence. Small molecule inhibitors as adjuvants in cancer immunotherapy aim to harness their immunomodulatory properties to optimize treatment outcomes. By modulating the tumor microenvironment, enhancing immune cell function, and increasing tumor sensitivity to immunotherapy, small molecule inhibitors have the potential to improve patient responses. This review discusses the evolving use of small molecule inhibitors as adjuvants in cancer treatment, highlighting their role in enhancing the efficacy of immunotherapy and the opportunities for advancing cancer therapies in the future. [ABSTRACT FROM AUTHOR]

Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy are examples of mainstream allopathic medicine treatments that effective for intermediate and advanced malignant tumors. The ongoing use of conventional allopathic medicine has resulted in adverse responses and drug resistance, which have hampered its efficacy. As an important component of complementary and alternative medicine, Chinese medicine has been found to have antitumor effects and has played an important role in enhancing the therapeutic sensitivity of mainstream allopathic medicine, reducing the incidence of adverse events and improving immune-related functions. The combined application of adjuvant Chinese medicine and mainstream allopathic medicine has begun to gain acceptance and is gradually used in the field of antitumor therapy. Traditional natural medicines and their active ingredients, as well as Chinese patent medicines, have been proven to have excellent therapeutic efficacy and good safety in the treatment of variousmalignant tumors. This paper focuses on the mechanism of action and research progress of combining the above drugs with mainstream allopathic medicine to increase therapeutic sensitivity, alleviate drug resistance, reduce adverse reactions, and improve the body's immune function. To encourage the clinical development and use of Chinese herb adjuvant therapy as well as to provide ideas and information for creating safer and more effective anticancer medication combinations, the significant functions of Chinese herb therapies as adjuvant therapies for cancer treatment are described in detail. [ABSTRACT FROM AUTHOR]

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy. [ABSTRACT FROM AUTHOR]

Extrapulmonary small cell carcinoma (EPSCC) is very rare with an incidence of 0.1 to 0.4% in the United states and the exact incidence in other regions is unknown. Anal canal involvement is extremely rare contributing to < 1% of all EPSCC. Inspite of its rarity, it is of clinical importance due to its aggressive nature. Most of the patients present with lungs and liver metastasis at diagnosis even in early stage tumors. It has a dismal survival rate of 58% at 6-month and 6% at 5-years in contrast to squamous cell carcinoma of anal canal. Exact ethiopathogenesis is unknown. Association with HIV has been seen like squamous cell carcinoma of anal canal. There is very little literature evidence and management is not clear like that of squamous cell carcinoma anal canal. Here we present the case of a 63 year old HIV positive male who presented with small cell carcinoma of anal canal to our institute and the challenges we faced in diagnosis and management. [ABSTRACT FROM AUTHOR]

Objective: In the present study, pre-operative magnetic resonance imaging (MRI) responses following neoadjuvant chemotherapy (NAC) administration were compared with postoperative pathological response rates. The study design was retrospective cross sectional method. Materials and Methods: Breast MRI is helpful in determining treatment plans, responses, and prospective survival analyses in breast cancer patients receiving neoadjuvant chemotherapy. A total of 39 patients receiving NAC between January 2019 and June 2020 were analyzed in the hospital. Treatment responses after NAC in patients with locally advanced who had not received any treatment before were evaluated with MRI. The longest diameter was recorded as well as the transfers of the primary tumor and axillary lymph node. The correlation of response rates obtained with the MRI with pathological specimen results was also examined. Results: When the pathological clinical response (pCR) was compared with the radiological response of the tumor and lymph node, the sensitivity was found to be 52.6% and 70.5%, and the accuracy was 64.1% and 51.2%, respectively. Conclusion: The preferred MRI techniques and sequence intervals, and the histopathological characteristics of the tumor increase the accuracy rates in reaching pathological complete response rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive breast cancer patients undergoing up-front surgery on their outcomes. Survival was not adversely affected by pN0(i+) and pN1mi in 1771 HER2-positive patients. However, in the case of pT1a-b HER2-positive breast cancers, a negative impact on recurrence-free survival was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without adjuvant chemotherapy. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based adjuvant chemotherapy for these patients. (1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5–64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04–5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03–6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients. [ABSTRACT FROM AUTHOR]

Lung cancer is a commonly diagnosed cancer and the leading cause of cancer-related deaths, posing a serious health risk. Despite new advances in immune checkpoint and targeted therapies in recent years, the prognosis for lung cancer patients, especially those in advanced stages, remains poor. MicroRNAs (miRNAs) have been shown to modulate tumor development at multiple levels, and as such, miRNA mimics and molecules aimed at regulating miRNAs have shown promise in preclinical development. More importantly, miRNA-based therapies can also complement conventional chemoradiotherapy, immunotherapy, and targeted therapies to reverse drug resistance and increase the sensitivity of lung cancer cells. Furthermore, small interfering RNA (siRNA) and miRNA-based therapies have entered clinical trials and have shown favorable development prospects. Therefore, in this paper, we review recent advances in miRNA-based therapies in lung cancer treatment as well as adjuvant therapy and present the current state of clinical lung cancer treatment. We also discuss the challenges facing miRNA-based therapies in the clinical application of lung cancer treatment to provide new ideas for the development of novel lung cancer therapies. [ABSTRACT FROM AUTHOR]

Approximately 6-10% of all breast carcinoma is metastatic at diagnosis, termed de novo metastatic breast carcinoma (dnMBC). Systemic therapy remains the first line of treatment in dnMBC, but there is growing evidence that adjuvant locoregional treatment (LRT) of the primary tumor increases progression-free and overall survival (OS). Although selection bias may exist, real-world data from nearly half a million patients show that patients are undergoing primary tumor removal because of the survival benefit. The main question for the advocates for LRT in this patient population is not whether primary surgery is beneficial in dnMBC patients, but rather who is a good candidate for it. Oligometastatic disease (OMD) is a distinct subset of dnMBC that affects a limited number of organs. A better OS can be achieved with LRT in breast cancer patients, especially in those with OMD, bone only, or favorable subtypes. Though there is currently no consensus among breast care specialists on how to treat dnMBC patients, primary surgery for dnMBC should be taken into consideration for a subset of patients following an extensive multidisciplinary discussion. [ABSTRACT FROM AUTHOR]

This single-center study aimed to retrospectively evaluate the survival outcomes of patients with FIGO stage I clear cell and serous uterine carcinoma according to the type of adjuvant treatment received. The data were collected between 2003 and 2020 and only patients with stage I clear cell or serous uterine carcinoma treated with primary surgery were included. These were classified into three groups: No treatment or brachytherapy only (G1), radiotherapy +/− brachytherapy (G2), chemotherapy +/− radiotherapy +/− brachytherapy (G3). In total, we included 52 patients: 18 patients in G1, 16 in G2, and 18 in G3. Patients in the G3 group presented with poorer prognostic factors: 83.3% had serous histology, 27.8% LVSI, and 27.8% were FIGO stage IB. Patients treated with adjuvant radiotherapy showed an improved 5-year overall survival (OS) (p = 0.02) and a trend towards an enhanced 5-year progression-free survival (PFS) (p = 0.056). In contrast, OS (p = 0.97) and PFS (p = 0.84) in the chemotherapy group with poorer prognostic factors, were similar with increased toxicity (83.3%). Radiotherapy is associated with improved 5-year OS and tends to improve 5-year PFS in women with stage I clear cell and serous uterine carcinoma. Additional chemotherapy should be cautiously considered in serous carcinoma cases presenting poor histological prognostic factors. [ABSTRACT FROM AUTHOR]

One of the major hallmarks of many cancer cells is dedifferentiated cells (immature cells) with little or no resemblance to normal cells. Besides the poor differentiation, malignant cells also have important features such as aggressiveness and resistance to different therapeutics. Differentiation potentiators hold great promise for cancer treatment. Dimethyl sulfoxide (DMSO) is a wellcharacterized pharmaceutical solvent. It is used as a component of numerous cancer therapeutic approaches, including cancer treatment and several approved cancer immune therapeutics such as Car-T cell therapy and the FDA-approved drug Mekinist (trametinib DMSO) for melanoma treatment. It is also biologically recognized as a pharmaceutical solvent and cryoprotectant. In the current literature, there are no mentions of DMSO's possible ability to potentiate therapeutic activity as a component of these cancer treatments. This review aimed to summarize scientific evidence and substantiate the concept that DMSO can contribute positively to the overall efficacy of cancer treatment as an adjuvant that is safe, inexpensive, and an effective differentiation-inducing therapeutic agent. [ABSTRACT FROM AUTHOR]

With the increasing complexity of modern oncological patient management and the growing amount of information needed from the pathologist, traditional narrative pathology reports (NR) do not suffice. Standardized synoptic reporting (SR) increases both completeness and readability. In the Netherlands SR for breast cancer was introduced in 2009. We explore the impact of synoptic reporting on breast cancer care. Using data from the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, a retrospective population-based cohort study was performed. Data of breast cancer resections from 2007 to 2014 were collected to compare NR and SR for all outcome measures. Kaplan-Meier analyses and log-rank testing were used to estimate overall survival. Over time there was an increase from 12% to 78.9% in the use of SR. SR resulted in higher completeness of pathology reports, particularly for hormone and HER2/neu receptor status. Although there was no difference in the administration of antihormonal therapy, anti-HER2 treatment was more frequently administered to eligible patients in the SR group. An effect on overall survival could not yet be confirmed on multivariate analysis. We demonstrate that SR has led to more complete pathology reports, which meets the needs for precision of information in breast cancer care. This is expected to improve communication and discussions between specialists regarding parameters important for adjuvant breast cancer treatment decisions. SR thereby improves breast cancer care and leads to improved allocation of treatment based on pathologic parameters and more personalized treatment regimens. • Synoptic reporting is increasingly used in breast cancer pathology. • Synoptic reporting results in higher completeness of pathology reports. • Synoptic reporting results in better treatment allocation. [ABSTRACT FROM AUTHOR]

Introduction. The non-sulfated natural compound, Hyaluronic acid (HA), is a mucopolysaccharide that has an essential role in cellular biology; it is a fundamental element of the living cell. HA plays an essential role in targeted drug delivery; it has recently acquired much attention because of various advantages like biocompatibility, biodegradability, non-immunogenicity, and non-toxicity. Methods. This narrative review is based on the literature searched with keywords Hyaluronic acid, Hyaluronic acid in cancer therapy, Hyaluronic acid in cancer targeting, Hyaluronic acid in drug targeting, was done on PubMed and Elsevier database from January to May 2021. Research published in the last five years was considered; however, no such timeline is followed in cross-referencing. Results. From the literature, it is found that HA can recognize distinct receptors that are abnormally revealed in large numbers on the outer surface of cancerous tissues or cells; hence can be used for conjugation with anticancer drugs, facilitating their enhanced therapeutic activity over the cancer cells than normal cells. It is also found that HA-based systems also provide increased stability and solubility of anticancer agents in biological surroundings. Based on these findings and advantages, HA is conjugated with various delivery systems like micelles, liposomes, hydrogels, nanoparticles, etc. As per recent research, the HA-based system provides immunotherapy, gene therapy, targeted chemotherapy, and combination therapy with enormous applications in the evolution of highly efficacious and cost-effective therapy for the ministration of cancer. Conclusion. In this context, various literatures on HA as adjuvant for drug delivery system for cancer targeting represents the HA as a potential adjuvant for cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of pancreatic cancer with chemotherapy followed by chemoradiotherapy prior to surgery in patients where the tumour is in contact with major abdominal blood vessels improves the ability to completely resect the tumour. This, in turn, improves patient survival after surgery, demonstrating that this treatment strategy is appropriate for such tumours. Background: Patients with borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC) have historically poor survival, even after curative pancreatic resection and adjuvant chemotherapy. Emerging evidence suggests that neoadjuvant chemoradiation (NCR) improves R0 resection rates in BR-PDAC patients. We evaluated the R0 resection rate, disease-free survival (DFS) and overall survival (OS) in our patients who underwent NCR for BR-PDAC at our institution. Methods: All patients who underwent NCR for BR-PDAC from January 2010 to March 2020 were included in the study. The patients received a variety of NCR regimens during the study period, and in patients with radiological evidence of tumour stability or regression, pancreatic resection was performed. The primary endpoint was the OS, and the secondary endpoints included patient morbidity, the R0 resection rate, histological parameters and the DFS. Results: The study included 29 patients (16 men and 13 women), with a median age of 65 years (range 46–74 years). Of these 29 patients, 17 received FOLFIRINOX and 12 received gemcitabine (GEM)-based NCR regimens. All patients received chemoradiation at the end of chemotherapy (range 45–56 Gy). R0 resection was achieved in 75% of the patients, with a higher rate noted in the FOLFIRINOX group. The median DFS was 22 months for the whole cohort but higher in the FOLFIRINOX group (34 months). The median OS for the cohort was 29 months, with a higher median OS noted for the FOLFIRINOX cohort versus the GEM cohort (42 versus 28 months). Conclusion: NCR, particularly FOLFIRINOX-based treatment, for BR-PDAC results in higher rates of R0 resection and an increased median DFS and OS, supporting its continued use in this patient group. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy is important to improve the prognosis of patients with advanced gastric cancer. However, it may result in postoperative complications (POCs). The aim of this study is to evaluate risk factors and prognostic impact of POCs in patients receiving neoadjuvant chemotherapy. Methods: We retrospectively collected clinical information of patients who underwent curative gastrectomy after receiving neoadjuvant chemotherapy between 2011 and 2018. Overall survival (OS) was analyzed using the Kaplan–Meier method. Logistic regression and Fisher's exact test were used to evaluate risk factors for complications. Results: A total of 176 patients were included in our study. The 3-year OS rates for the complication group (n = 30) and non-complication group (n = 146) were 36.7% and 52.7%, respectively (p = 0.0294). Age, BMI, multivisceral resection and operation time were independent risk factors for POCs in patients. Patients with multivisceral resection were more likely to suffer from grade III-IV complications (p = 0.026). Inflammation complications might occur in patients with high BMI (p = 0.017). Low preoperative albumin seemed to be a risk factor for leakage complications (p = 0.033). Conclusions: Our study revealed that patients with POCs had a poor prognosis and we identified the risk factors for complications so that POCs can be avoided in time. [ABSTRACT FROM AUTHOR]

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1–2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the three most common types of cancer in Germany. Approximately 30% of these cancers are located in the rectum, corresponding to about 18 000 new cases per year. Methods: This review is based on publications retrieved by a selective search in the PubMed database, including current guidelines and recommendations. Results: Specialized imaging, particularly magnetic resonance imaging, is essential for treatment planning. In very early stages of this disease, tumors without risk factors can be excised locally. Otherwise, radical surgical resection with lymphadenectomy remains the standard treatment, and can be performed either minimally invasive or open. At present, neoadjuvant treatment plans are evolving in the direction of total neoadjuvant therapy. In addition, recent studies investigate whether the improved efficacy of neoadjuvant therapy might now enable patients with a complete clinical remission to be spared from surgical resection (organ-preserving watch-and-wait strategy). Conclusion: The treatment of rectal cancer is a prime example of an interdisciplinary, multimodal approach. In the past, the focus was mainly on improving oncologic outcomes; at present, increasing attention is being devoted to the patients' quality of life as well and the functional aspects of the various modes of treatment. [ABSTRACT FROM AUTHOR]

Throughout the United States, cancer remains the second leading cause of death. Traditional treatments induce significant medical toxic effects and unpleasant adverse reactions, making them inappropriate for long-term use. Consequently, anticancer-drug resistance and relapse are frequent in certain situations. Thus, there is an urgent necessity to find effective antitumor medications that are specific and have few adverse consequences. Curcumin is a polyphenol derivative found in the turmeric plant (Curcuma longa L.), and provides chemopreventive, antitumor, chemo-, and radio-sensitizing properties. In this paper, we summarize the new nano-based formulations of polyphenolic curcumin because of the growing interest in its application against cancers and tumors. According to recent studies, the use of nanoparticles can overcome the hydrophobic nature of curcumin, as well as improving its stability and cellular bioavailability in vitro and in vivo. Several strategies for nanocurcumin production have been developed, each with its own set of advantages and unique features. Because the majority of the curcumin-based nanoformulation evidence is still in the conceptual stage, there are still numerous issues impeding the provision of nanocurcumin as a possible therapeutic option. To support the science, further work is necessary to develop curcumin as a viable anti-cancer adjuvant. In this review, we cover the various curcumin nanoformulations and nanocurcumin implications for therapeutic uses for cancer, as well as the current state of clinical studies and patents. We further address the knowledge gaps and future research orientations required to develop curcumin as a feasible treatment candidate. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cavity carcinoma (OCC) is the 11th most frequently diagnosed cancer; despite a multimodal treatment, locally advanced OCC, managed by surgery and adjuvant therapies, remains at high risk of recurrence, with a 5-year overall survival (OS) of 51%. The efficacy of postoperative chemotherapy in addition to radiotherapy (POCRT) in low–intermediate risk OCC is a controversial matter in the absence of high-risk features (ENE, R1). To establish the role of POCRT in a population with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE), we performed a systematic review and meta-analyses focused on OS, disease-free survival (DFS), and local-recurrence-free survival (LRFS). Thirteen studies met the inclusion criteria and were included in the quantitative meta-analyses. Our preliminary results are in favor of POCRT in terms of OS but not conclusive for DFS and LRFS. Further analyses are suggested. When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2–5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5–79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8–86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1–86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan–Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions. Adrenocortical cancer is a rare and poor prognostic malignant tumor. The definitions of prognostic factors in localized and metastatic diseases are important. In this paper, we defined the clinical features, management, and prognostic factors related to survival in patients with metastatic and nonmetastatic ACC. Cox regression analysis showed that age, Ki67 value, ECOG PS, and hormonal activity were significantly associated with survival in patients with nonmetastatic disease. Only patients who underwent surgery had significantly better OS compared with patients without surgery in univariate analyses of metastatic disease. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess whether follow-up of patients with operative breast cancer at cancer centres (CCs) improved prognosis compared with follow-up by family physicians (FPs). Methods: The study included 254 patients who relapsed within 7 years from the first postoperative period. The patients were divided into two groups according to the follow-up facility: the CC and FP groups (the follow-up of patients was structured in the same way between FPs and CCs). There are 146 and 108 cases of recurrence in the CC and FP groups, respectively. The analysis targets of the two groups were determined using the propensity matching method based on the following 7 factors: oestrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, St. Gallen category, menopausal status, surgical procedure, and receipt of postoperative chemotherapy at the time of surgery. Overall survival (OS) in both groups was analysed using the Kaplan-Meier method and compared using the log-rank test. Results: Overall, 97 patients each in the CC and FP groups who relapsed were analysed using the propensity matching method. The median recurrence-free survival periods were 1,676 and 994 days in the FP and CC groups, respectively, and were significantly longer in the FP group. However, the median OS starting from the day of surgery was 3,424 and 2,794 days in the FP and CC groups, respectively, with no significant difference. Conclusion: This study revealed that regular follow-up at CCs did not improve survival compared with regular follow-up by FPs. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common gynecological malignancy in developed countries. The management is primarily surgical, but adjuvant treatment may be indicated after surgery, according to the risk of recurrence. This review will focus on the prognostic risk groups presented in the 2020 ESGO/ESTRO/ESP guidelines and the ongoing trials based on new molecular markers that will help to get a more personalized cancer medicine. [ABSTRACT FROM AUTHOR]

Colon cancer is currently a highly prevalent cancer with a high mortality rate worldwide. Modern medical technology provides a range of treatments for colon cancer through different means, and research on the modulating adjuvant treatment of colon cancer with Chinese medicine is currently undergoing continuous theoretical and practical exploration to find highly effective herbal remedies to modulate, alleviate or treat the disease. The present study reviews different aspects of colon cancer in relation to different factors and the modulating adjuvant treatment of colon cancer with Chinese medicine. [ABSTRACT FROM AUTHOR]

Heating cancer cells over an extended period of time, referred to as hyperthermia, has been proven to enhance the effects of chemotherapy and radiotherapy without inducing additional toxicity or undesirable side effects, and is therefore considered a highly valuable adjuvant therapy in cancer treatment. In this work, a model predictive control (MPC) setup is developed for improving performance and robustness in regulating the temperature for magnetic-resonance-guided high-intensity focused ultrasound (MR-HIFU) hyperthermia treatments. The proposed control design incorporates a disturbance estimator as encountered in offset-free MPC that is able to remove the steady-state temperature error caused by plant-model mismatch. For the considered healthcare application, such modeling errors are inevitable in practice due to the high variability of tissue properties in patients, some of which even exhibit time- and temperature-dependent behavior due to the body’s thermoregulatory response, combined with the fact that extensive model identification is undesirable in the clinic. The controller’s performance is demonstrated by means of in vivo experiments on a porcine thigh muscle using a clinical MR-HIFU treatment setup. [ABSTRACT FROM AUTHOR]

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side-effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non-toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre-clinical and clinical studies using high-dose IVC as anti-cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high-dose vitamin C in cancer treatment is presented and recommendations for further research are discussed. [ABSTRACT FROM AUTHOR]

Introduction: The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. Methods: PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). Results: Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10–21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. Conclusions: ART was shown to improve OS in all studies and in those selected for their reliable comparability. [ABSTRACT FROM AUTHOR]

Background: Breast cancer, a malignant disorder, occurs in epithelial tissue of the breast glands and ducts. Endocrine therapy is commonly applied as an important adjuvant treatment for breast cancer, but it usually induces a variety of side effects. Chinese Medicines (CM) has therapeutic effect on reducing adverse effects of the endocrine therapy in many clinical studies. But strong evidence is still limited on the efficacy and safety of CM combined western medicines (CM-WM) for breast cancer. Objective: To study the efficacy and safety of CM-WM as an adjuvant treatment for reducing side effects induced by endocrine therapy in breast cancer patients. Method: We searched relevant clinical studies in PubMed and the Chinese National Knowledge Infrastructure (CNKI) databases up to February 28, 2021 and only Randomized Controlled Trials (RCTs) were included. There were no limitations on the languages. We extracted data from the included RCTs, assessed study quality, conducted meta-analyses by RevMan 5.4 and compared the pooled Risk Ratios (RR) or Mean Difference (MD) with 95% CIs. Results: In total 28 trials involving 1,926 participants were included. Six RCTs compared CM-WM with CM placebo-WM, while 22 RCTs compared CM-WM with WM alone. No study compared CM-WM with no treatment. Meta-analysis showed that CM-WM treatment significantly improved quality of life (MD = 0.73, 95% CI = 0.11–1.35, P = 0.02) when compared with CM placebo-WM treatment. When compared with WM treatment alone, CM-WM treatment significantly improved bone mineral density (MD = 0.24, 95% CI = 0.13–0.35, P <0.0001), TCM syndrome score (MD = −5.39, 95% CI = −8.81 to −1.97, P = 0.0002), Kupperman Scale (MD = 0.24, 95% CI = −2.76 to −1.94, P < 0.0001), Karnofsky Performance Scale (MD = 3.76, 95% CI = 1.64–5.88, P = 0.0005), quality of life (MD = 3.01, 95% CI = 1.00–5.02, P = 0.003), and pain relief (MD = 2.10, 95% CI = 0.72–3.48, P < 0.0001). Compared with WM, CM-WM significantly decreased incidence of TCM symptoms (nausea, vomiting, fatigue, etc.) (RR = 1.60, 95% CI = 1.40–1.84, P < 0.0001). For safety, serum calcium, estradiol, ALP, and blood CD3, CD4 and CD8 counts were not significantly difference between two treatments (P > 0.05). Serious side effects or reactions were not reported in all included studies. Conclusion: The adjunctive use of CM reduced the endocrine therapy associated adverse events, including bone mineral density loss, perimenopausal symptoms, poor quality of life, pain and impaired immune function. But large-scale and high quality RCTs are needed to support the application of CM-WM therapy. [ABSTRACT FROM AUTHOR]

Standardized pathological evaluation of the regression assessment of neoadjuvant pancreatic cancer is necessary to improve prognostication and compare treatment outcomes in clinical trials. However, appropriate tissue sampling from surgically resected pancreatic cancer after neoadjuvant therapy has not been elucidated. We compared the tumor regression scores in the largest cancer slide determined macroscopically or histologically. We reviewed all slides and macroscopic photos of cut surfaces from resected pancreas of patients treated with neoadjuvant chemotherapy (n = 137; chemoradiotherapy or chemotherapy). The tumor regression scores (the Evans, College of American Pathologists, Japanese Pancreas Society grading systems, and Area of Residual Tumor [ART] score) were evaluated for the largest tumor slide determined by macroscopy or histologically as well as all slides from the resected pancreas. The largest cancer slides determined macroscopically and histologically were discrepant in 26% of the cases. Cancer cells were not detected in the largest macroscopically defined cut slides in 3%. Only ART scores assessed in the largest histological slides displayed significant difference in overall survival. We recommend obtaining the largest histological slides to provide adequate assessment for regression of neoadjuvant-treated pancreatic cancer. Sufficient sampling to detect the largest histological slides would be mandatory. [ABSTRACT FROM AUTHOR]

Advances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM. [ABSTRACT FROM AUTHOR]

Patients who have refractory cancer pain suffer both physically and psychologically. Cancer pain management has improved over the past few decades. However, the treatment of refractory cancer pain is still challenging all over the world. Intraspinal analgesia has become an effective strategy to treat refractory pain in patients with cancer. In this report, we present a patient receiving a large dose of intrathecal opioids for refractory cancer pain, and who is also afflicted with pain-induced depression. Dexmedetomidine (DEX) was used as part of a multimodal analgesic regimen that successfully alleviated both the patient's pain and depression. An intrathecal infusion of DEX may serve as an adjuvant drug in the treatment of cancer pain and pain-related depression. [ABSTRACT FROM AUTHOR]

The predictive value of tumor mutational burden (TMB), alone or in combination with an immune gene expression profile (GEP), for response to neoadjuvant therapy in early triple negative breast cancer (TNBC) is currently not known, either for immune checkpoint blockade (ICB) or conventional chemotherapy. We obtained both whole exome sequencing and RNA-Seq data from pretreatment samples of 149 TNBC of the recent neoadjuvant ICB trial, GeparNuevo. In a predefined analysis, we assessed the predictive value of TMB and a previously developed immune GEP for pathological complete remission (pCR). Median TMB was 1.52 mut/Mb (range 0.02–7.65) and was significantly higher in patients with pCR (median 1.87 versus 1.39; P = 0.005). In multivariate analysis, odds ratios for pCR per mut/Mb were 2.06 [95% confidence intervals (CI) 1.33–3.20, P = 0.001] among all patients, 1.77 (95% CI 1.00–3.13, P = 0.049) in the durvalumab treatment arm, and 2.82 (95% CI 1.21–6.54, P = 0.016) in the placebo treatment arm, respectively. We also found that both continuous TMB and immune GEP (or tumor infiltrating lymphocytes) independently predicted pCR. When we stratified patients in groups based on the upper tertile of TMB and median GEP, we observed a pCR rate of 82% (95% CI 60% to 95%) in the group with both high TMB and GEP in contrast to only 28% (95% CI 16% to 43%) in the group with both low TMB and GEP. TMB and immune GEP add independent value for pCR prediction. Our results recommend further analysis of TMB in combination with immune parameters to individually tailor therapies in breast cancer. • Tumor mutational burden (TMB) predicts pCR after neoadjuvant treatment in early triple negative breast cancer. • The predictive value of TMB was found both for immune checkpoint inhibition with chemotherapy and for chemotherapy alone. • Both TMB and an immune gene expression profile add independent value for pCR prediction in multivariate analysis. [ABSTRACT FROM AUTHOR]

Aim: The optimal treatment approach for adenocarcinoma of the rectosigmoid junction remains unclear. The aim of this work was to compare outcomes of neoadjuvant chemoradiation (NCR) and adjuvant chemotherapy (AC) treatment for cancer of the rectosigmoid junction. Method: This was a nationwide, retrospective cohort study (2004–2015) using hospital‐based cancer outcomes data (National Cancer Database). All patients who underwent resection with curative intent for locally advanced [American Joint Committee on Cancer (AJCC) Stages II and III] adenocarcinoma of the rectosigmoid junction were included. Exclusion criteria were age less than 18 or over 75 years, Charlson–Deyo score > 2, AJCC Stages I and IV and unstaged tumours. Treatment with NCR was compared with treatment with AC, the primary outcome being overall survival. Other end‐points were resection margin status, the presence of lymphovascular invasion and postoperative length of stay. Results: A total of 2828 patients were included in this study, of whom 1701 (59.7%) received NCR. NCR was more frequently utilized in patients who were black (10.3% vs 7.6%, P < 0.05) and underwent treatment at academic institutions (37.9% vs 22.5%, P < 0.05). Treatment with NCR did not differentially influence survival following risk adjustment (hazard ratio 1.17, CI 0.98–1.40; P = 0.085). NCR was independently associated with a decreased likelihood of a positive resection margin (OR 0.44, CI 0.33–0.58; P < 0.001) and lymphovascular invasion (OR 0.51, CI 0.40–0.67; P < 0.001). However, treatment with NCR was associated with the need for prolonged hospitalization compared with AC (7.3 days vs 6.5 days; P = 0.015). The study was limited by its retrospective design, external validity and risk of tumour misclassification. Conclusion: NCR currently seems to be favoured over AC for the management of locally advanced adenocarcinoma of the rectosigmoid junction. This approach may not be justified as NCR is associated with prolonged hospitalization needs without a clear survival benefit when compared with AC. Prospective studies are warranted to definitively compare outcomes of NCR and AC in this patient population. [ABSTRACT FROM AUTHOR]

To evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. One hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. The median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. Marginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation. • Locoregional recurrences are common for oral cavity carcinomas. • Target selection/delineation is challenging for adjuvant radiotherapy. • Analysis shows the occurrence of marginal and out-of-field recurrences. • For oral tongue carcinomas the undissected/unirradiated contralateral neck is at risk. • A generous approach to radiotherapy target selection/delineation is required. [ABSTRACT FROM AUTHOR]

The article offers information on the glioblastoma multiforme (GBM), the commonest primary brain malignant tumor eludes a cure. It mentions that radiotherapy (RT) has consistently shown to improve OS compared to best supportive care in GBM patients; and also mentions that patients who were alive at the time of last follow-up were classified as censored observations.

Background: This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy and chemoradiotherapy in stage II or stage III thoracic esophageal squamous cell carcinoma (TESCC) patients who underwent curative (R0) esophagectomy. Methods: A total of 272 TESCC patients who underwent radical esophagectomy from 2007 to 2016 were included in this retrospective analysis. All cases were pathologically confirmed with stage II or III disease and 148 patients received postoperative chemoradiotherapy (CRT), while the remaining 124 patients received postoperative radiotherapy (RT) alone. Results: In CRT and RT groups, the three‐year overall survival rates were 51.3 versus 31.5% (P < 0.01) and the median overall survival (OS) was 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively (P = 0.213). Three‐year disease‐free survival rates (DFS) were 30.5% versus 15.9% (P = 0.008), while the median DFS times were 26 months (95% CI, 17.7 to 34.3 months) and 19 months (95% CI, 16.4 to 21.6 months), respectively (P = 0.156). Univariate and multivariate analyses showed AJCC (American Joint Committee on Cancer seventh edition) stage and N stage were independent prognostic factors for overall survival, while the N stage was an independent prognostic factor for disease‐free survival. Conclusions: Postoperative chemoradiotherapy led to one‐ and three‐year overall survival benefits along with an obvious increase in treatment side effects for stage II to III TESCC patients, with no further improvement in five‐year survival. However, the chemoradiotherapy benefits mainly favor stage III,number of resected lymph nodes less than 15, younger (less than 60 years old) and smoking patients. [ABSTRACT FROM AUTHOR]

Background: The NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology (NCCN guidelines) recommend radical resection for T1-2N0M0 patients with limited-stage small cell lung cancer (LS-SCLC). However, only about 5% of patients with small cell cancer (SCLC) were initially diagnosed as T1-2N0M0. The purpose of our study was to analyze and compare the effects of the comprehensive treatment including radical surgery and concurrent chemoradiotherapy on the prognosis of patients with LS-SCLC. Methods: We comprehensively reviewed the medical data of patients with SCLC diagnosed by pathology in our hospital from January 2011 to April 2018. The Ethics Committee of West China Hospital of Sichuan University approved the study. Finally, 50 patients with good follow-up and complete medical data were selected as the surgical group (S group). According to the clinical characteristics of the patients in the S group, 102 LS-SCLC patients who received concurrent chemoradiotherapy in the same period were included in the CCRT group (concurrent chemoradiotherapy group) as the control group. Then according to the orders of the adjuvant treatments, the patients in the S group were divided into the SA group (radical surgery + adjuvant chemotherapy + adjuvant radiotherapy group, 30 cases in total) and the NS group (neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy group, 20 cases in total) for subgroup analysis. The SPSS 23.0 software was used for statistical analysis, and the t test was used for group comparison; Kaplan-Meier was used for survival analysis. P < 0.05 demonstrates a statistically significant difference. Results: The median progress-free survival (PFS) in the S group (73 months) was significantly better than that in the CCRT group (10.5 months, P < 0.0001), and the median overall survival (OS) in the S group (79 months) was also significantly better than that in the CCRT group (23 months, P < 0.0001). Subgroup analysis showed that there was no significant difference between the NS group and the SA group. Conclusions: For LS-SCLC patients, the comprehensive treatment including radical surgery (radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy/neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy)may be superior to concurrent chemoradiotherapy. [ABSTRACT FROM AUTHOR]

The bevacizumab-Avastin® adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51–10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07–1.55; P = 0.008] and 1.16 (95% CI 0.99–1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95–1.39; P = 0.147) and 1.1 (95% CI 0.93–1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. NCT00112918. • With a median follow-up of 6.73 years S-AVANT confirms the initial AVANT report, in patients with stage III Colon Cancer. • No benefit of bevacizumab addition to FOLFOX4 Cancer was observed in terms of Disease Free Survival. • In this exploratory analysis, bevacizumab addition to FOLFOX4 shows a negative statistically significant effect on OS. • This effect on OS was without increase in non-Colon Cancer related deaths. • Bevacizumab should not be used in adjuvant treatment of patients with curatively resected stage III Colon Cancer. [ABSTRACT FROM AUTHOR]

Background and Purpose: Even though new cancer therapies have improved the overall survival, in some cases they have been associated with adverse effects, including increased cardiotoxicity. The purpose of the present study was to assess the cardiovascular effects of adjuvant chemotherapy for colorectal cancer and mainly the impact on arterial stiffness indices. Material and Methods: A total of 70 patients with non-metastatic colorectal cancer who were treated either with FOLFOX (n=16) or with XELOX (n=54) adjuvant chemotherapy were included in the study. All patients were subjected to full cardiovascular evaluation at the beginning and the end of chemotherapy. Arterial stiffness was assessed by means of pulse wave velocity (PWV) and augmentation index (Aix) and full laboratory examinations were conducted prior to, and soon after, the termination of chemotherapy. Results: Patients exhibited significantly higher levels of carotid-radial PWV, carotid femoral RWV and Aix post-chemotherapy (p< 0.001); these findings remained significant when examined separately in each treatment subgroup (FOLFOX, XELOX). The observed changes were independent of treatment regimen and baseline patient characteristics. Univariate regression analyses showed that baseline PWVc-r and PWVc-f were the only factors associated with PWVc-r and PWVc-f change, while Aix change was independent of its baseline value. Conclusion: There is a clear burden in arterial stiffness indices post-adjuvant chemotherapy for colorectal cancer in both chemotherapy groups. This is a finding of important clinical significance, however more prospective studies are required in order to encode the possible mechanisms involved. [ABSTRACT FROM AUTHOR]

We conducted a retrospective exploratory analysis to evaluate the effects of baseline tumour immune infiltrate on disease-free survival (DFS) outcomes in patients with fully resected stage IIC–IIIC melanoma receiving adjuvant vemurafenib monotherapy or placebo in the BRIM8 study. BRIM8 was a phase III, international, double-blind, randomised, placebo-controlled study. Eligible patients with BRAF V600 mutation–positive, completely resected melanoma were randomly assigned to oral vemurafenib (960 mg twice daily) or matching placebo for 52 weeks. The primary end point was DFS. The association of CD8+ T-cell infiltration and programmed death ligand 1 (PD-L1) expression with DFS, as measured by immunohistochemistry, was explored retrospectively. Four hundred ninety-eight patients were randomly assigned to receive adjuvant vemurafenib (n = 250) or placebo (n = 248); tumour samples were available for biomarker analysis for approximately 60% of patients. In the pooled biomarker population, placebo-treated patients with <1% CD8+ T cells in the tumour centre had shorter median DFS than those with ≥1% CD8+ T cells (7.7 versus 47.8 months). DFS benefit from vemurafenib versus placebo was greater in patients with <1% CD8+ T cells [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.34–0.92) than in patients with ≥1% CD8+ T cells (HR 0.77; 95% CI 0.48–1.22). Likewise, median DFS was shorter among placebo-treated patients with <5% versus ≥5% PD-L1+ immune cells (IC) in the tumour (7.2 versus 47.8 months). A greater DFS benefit with vemurafenib versus placebo was observed in patients with <5% PD-L1+IC (HR 0.36; 95% CI 0.24–0.56) than in patients with ≥5% PD-L1+IC (HR 0.99; 95% CI 0.58–1.69). The presence of CD8+ T cells and PD-L1+IC are favourable prognostic factors for DFS. Treatment with adjuvant vemurafenib may overcome the poor DFS prognosis associated with low CD8+ T-cell count or PD-L1 expression. NCT01667419 • This study confirms the positive prognosis associated with immune/PD-L1+ tumour infiltrate in BRAF mutant melanoma. • The benefit of adjuvant anti–PD-1 therapy in preventing recurrence is less evident in patients with PD-L1–negative tumours. • Adjuvant vemurafenib may overcome the poor prognosis associated with reduced immune/PD-L1–positive tumour infiltrate. • This study suggests that BRAF inhibition may benefit patients with lower levels of baseline immune infiltrate. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease. Increasing evidence revealed, a variety of internal and external factors are associated with initiation and progression of cervical cancer pathogenesis. Human papilloma virus infection is found as a major cause of cervical cancer. Other molecular and biochemical alterations as well as genetic and epigenetic changes are related cervical cancer progression. Current treatment options often have severe side effects and toxicities thus, new adjuvant agents having synergistic effects and ability to decrease different side effects and toxicities are needed. Melatonin is an indolamine compound secreted from the pineal gland which shows wide range anticancer activities. A large amount of studies indicated inhibitory effects of melatonin against various types of cancers. In addition, experimental evidence reports inhibitory effects of melatonin as an adjuvant therapy on cervical cancer by targeting a sequence of different molecular mechanisms. Herein, for first time, we summarized anticervical cancer effects of melatonin and its underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2‐positivity (HER2) has a prognostic and predictive role in breast cancer. Trastuzumab, an anti‐HER2 therapy, has a crucial role in a curative setting in Stage I, II and III breast cancer. In recent years, more anti‐HER2 agents have been tested in clinical trials. Newer dosing strategies and combination approaches give us a plethora of options to treat a patient with early‐stage and locally advanced breast cancer. It has led to the possibility of providing a risk‐adapted treatment for patients with HER2‐positive breast cancer. In order to reduce overtreatment and protect patients from adverse effects, a deescalation framework can be used in patients at lower risk for recurrence. Similarly, in those with greater risk for recurrence, escalation of therapy can be considered with the goal of achieving a cure. In this narrative review, we aim to provide a critical appraisal of the recent research findings in the management of early‐stage and locally advanced breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Today, there is a global consensus that adjuvant treatment is mandatory for stage II and III gastric cancer. What remains controversial, however, is what constitutes the best adjuvant therapy. A comprehensive review including published papers, doi documents, and abstracts from the ASCO annual meeting was undertaken to develop this updated review.Areas covered: Adjuvant treatments for stage II or more advanced and potentially curable gastric and gastroesophageal junction (GEJ) adenocarcinoma are, exclusively, reviewed and discussed.Expert opinion: The role of radiation is not yet established for gastric and GEJ cancers. Postoperative chemoradiotherapy offers no survival advantage over chemotherapy alone for patients who undergo D2 surgery. It is not yet clear if neoadjuvant chemoradiotherapy is better than adjuvant chemotherapy. Individualized treatment plans should be determined for many patients as efficacy depends on tumor histology, and toxicity varies enormously among effective options. [ABSTRACT FROM AUTHOR]

Curcumin (CU), an edible natural pigment from Curcuma Longa , has demonstrated extensive anti-tumor effect in vivo and in vitro. With the property of reversing drug resistance and low toxicity, CU has been considered to develop a new adjuvant chemotherapy protocol of cancer. However, the poor stability, solubility, in vivo bioavailability and weak activity of CU greatly limit its clinical application. Therefore, CU analogues have been extensively studied. Starting from the study of natural CU analogues, multiple approaches are being sought to obtain more stable, soluble and effective analogues of CU. This review focuses on the progress of these approaches to more potent CU analogues. Image 1 • The study of curcumin analogues for cancer treatment has received extensive attention due to the unique physiological activities and defects of curcumin itself. • The discussed natural analogues and artificial analogues of curcumin. • Comparison of the difference in structure and activity between natural analogues and curcumin. • The progress of artificial modification for stability, solubility and cyto-toxicity. [ABSTRACT FROM AUTHOR]

Background Chemotherapy has improved outcomes in early-stage breast cancer, but treatment practices vary, and use of acute care is common. We conducted a pan-Canadian study to describe treatment differences and the incidence of emergency department visits (EDVS), EDVS leading to hospitalization (EDVHS), and direct hospitalizations (HS) during adjuvant chemotherapy. Methods The cohort consisted of women diagnosed with early-stage breast cancer (stages I–III) during 2007–2012 in British Columbia, Manitoba, Ontario, or Nova Scotia who underwent curative surgery. Parallel provincial analyses were undertaken using linked clinical, registry, and administrative databases. The incidences of EDVS, EDVHS, and HS in the 6 months after treatment initiation were examined for patients treated with adjuvant chemotherapy. Results The cohort consisted of 50,224 patients. The proportion of patients who received chemotherapy varied by province, with Ontario having the highest proportion (46.4%), and Nova Scotia, the lowest proportion (38.0%). Age, stage, receptor status, comorbidities, and geographic location were associated with receipt of chemotherapy in all provinces. Ontario had the highest proportion of patients experiencing an EDV (36.1%), but the lowest proportion experiencing h (6.4%). Conversely, British Columbia had the lowest proportion of patients experiencing an EDV (16.0%), but the highest proportion experiencing H (26.7%). The proportion of patients having an EDVH was similar across provinces (13.9%–16.8%). Geographic location was associated with EDVS, EDVHS, and HS in all provinces. Conclusions Intra- and inter-provincial differences in the use of chemotherapy and acute care were observed. Understanding variations in care can help to identify gaps and opportunities for improvement and shared learnings. [ABSTRACT FROM AUTHOR]

The article informs about the perfusion computed tomography (CT) radiomics as potential prognostic biomarker in head and neck squamous cell carcinoma. Topics discused include correlation to angiogenesis and hypoxia-related blood serum biomarkers; fractions using an intensity modulated radiotherapy technique in combination with concurrent cisplatin; and Secreted serum components can be associated with treatment efficacy and potentially participate in the generation of resistance mechanisms.

Purpose: Triple negative breast cancer (TNBC) patients frequently receive neoadjuvant chemotherapy (NAC). Only 50% will achieve pathological complete response (pCR). In this retrospective study, we evaluated TNBC outcomes with NAC vs. AC. Methods: Patients with stages II and III TNBC treated with NAC or AC between 2010 and 2013 were identified from the National Cancer Database. Baseline characteristics were compared with χ2 and two sample t tests. Kaplan-Meier survival analyses were computed in patients treated with NAC or AC, and log-rank tests used to examine differences. Unadjusted analyses of trends in proportions over time were performed using Cochran–Armitage tests. Log-binomial models were applied to estimate relative risks of non-pCR following NAC. Results: Of 19,151 patients, 5,621 (29.4%) received NAC, 13,530 (70.6%) received AC. NAC treated patients had worse OS compared to AC treated patients (73.4% vs. 76.8%; p<0.0001). pCR rate following NAC was 47.4%, and was associated with improved 5 year OS compared to non-pCR (86.2% vs. 62.3%; p<0.0001). In patients who received NAC, age, black race, clinical stage, diagnosis year, and Charlson-Deyo comorbidity score predicted non-pCR status. Use of NAC increased over the study period from 2010 to 2013 (27.8% - 31.2%; p = 0.0002). Conclusions: NAC may be inferior to AC in TNBC, likely related to the high frequency of non-pCR following NAC. It is unclear if removing the primary tumor prior to chemotherapy will have a beneficial biologic impact on therapeutic efficacy. These data should be considered hypothesis-generating as it is possible that the findings are due to selection bias, as physicians may use NAC for TNBC patients with more advanced local disease. Although, NAC still has a role in TNBC, developing biomarkers to identify patients likely to achieve pCR and benefit from NAC is an urgent need. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy is required for cholangiocarcinoma (CCA) patients after surgical treatment. Gemcitabine and gemcitabine plus cisplatin are considered the appropriate regimen; however, the response spectrum to chemotherapy differs between patients. Thus, the present study aims to evaluate the response pattern of individual CCA patients by using an in vitro method, histoculture drug response assay (HDRA), to predict the chemosensitivity of individual patients in a prospective study. Moreover, we also investigate the expression of gemcitabine and cisplatin sensitivity factors in CCA tissues in the same cases. Based on the dose response curve, 1000 and 1500 μg/ml of gemcitabine were used as the testing concentrations. For cisplatin, concentrations of 20 and 25 μg/ml were selected for testing and for the combination regimen, 1000 μg/ml of gemcitabine and 20 μg/ml of cisplatin were chosen. The median %IR of each drug was measured as the cut-off to categorize the response pattern into response and non-response groups. In addition, we compared the effectiveness of the chemotherapy regimens between gemcitabine alone and gemcitabine plus cisplatin. The %IR of the combination of gemcitabine and cisplatin was significantly higher than gemcitabine alone. The relationship between the expression level of gemcitabine and cisplatin sensitive factors and the individual response pattern as well as clinicopathological data of CCA patients were analyzed. The results indicated that a low expression of the gemcitabine sensitive factor hENT-1 was significantly associated with the non-response group in vitro (p = 0.002). Moreover, the low expression of hENT-1 was also significantly associated with advanced stages CCA in the patients (p = 0.025). A low expression of MT and ERCC1 was significantly correlated with the response group in the in vitro experiments (p = 0.015 and p = 0.037 for MT and ERCC1, respectively). Therefore, HDRA may serve as an aid to selecting chemotherapy, and the expression of hNET-1, MT and ERCC1 may serve as biomarkers for predicting chemotherapy success. [ABSTRACT FROM AUTHOR]

Pathological assessments of the treatment effect are critical for predicting patient outcomes after surgery. This study included 82 localized pancreatic cancer, 40 of whom were treated with neoadjuvant therapy (NAT) using four courses of gemcitabine plus nab-paclitaxel (GnP) followed by pancreatectomy (GnP group). The remaining 42 patients were treated with upfront pancreatectomy (UP) followed by adjuvant chemotherapy (UP group). We reviewed clinicopathological data of these patients to assess differences between the GnP and UP groups and further evaluate the prognostic impact of residual tumors after GnP treatment. Adjuvant treatment (S1, GnP or gemcitabine) was administered for 36 patients in the GnP group and 33 patients in the UP group. Compared to the UP group, the GnP group showed lower serum CA19-9 levels, microscopic tumor volume, and tumor-stroma ratio and decreased number of lymph node metastasis and vascular invasion. Higher incidence of encapsulating fibrosis was observed in the GnP group than in the UP group. Relative to the UP group (69%), a higher R0 rate was observed in the GnP group (85%). As for prognosis, encapsulating fibrosis was correlated with the overall survival of patients in the GnP group. However, overall survival did not show any correlation with other clinicopathological factors, including tumor reduction ratio (determined by computed tomography) and tumor regression grade (determined following criteria of Evans’ grading system or those of the College of American Pathologists). In conclusion, the present study revealed that GnP-induced encapsulating fibrosis could predict patients’ outcome. Nevertheless, large cohort studies are warranted to further evaluate the prognostic value of fibrosis, possibly with the help of imaging and biomarkers. [ABSTRACT FROM AUTHOR]