Systemic treatment for advanced pancreatic cancer

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

Advances in translational therapy for locally advanced gastric cancer

Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.

Neoadjuvant treatment of rectal cancer: Where we are and where we are going

Locally advanced rectal cancer requires a multidisciplinary approach based on total neoadjuvant treatment with radiotherapy(RT)and chemotherapy(ChT),followed by deferred surgery.Currently,alternatives to the standard total neoadjuvant therapy(TNT)are being explored,such as new ChT regimens or the introduction of immunotherapy.With standard TNT,up to a third of patients may achieve a complete pathological response(CPR),potentially avoiding surgery.However,as of now,we lack predictive markers of response that would allow us to define criteria for a conservative organ strategy.The presence of muta-tions,genes,or new imaging tests is helping to define these criteria.An example of this is the diffusion coefficient in the diffusion-weighted sequence of magnetic resonance imaging and the integration of this imaging technique into RT treatment.This allows for the monitoring of the evolution of this coefficient over successive RT sessions,helping to determine which patients will achieve CPR or those who may require intensification of neoadjuvant therapy.

Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.

The transition and current pattern of drug therapy for advanced gastric cancer

Gastric cancer is one of the most common malignant tumors in the world.Its incidence ranks fifth among all malignant tumors worldwide and is the third leading cause of death among cancer patients.Surgery is currently considered to be the only radical treatment.However,the low rate of early diagnosis means that most patients have an advanced-stage disease at diagnosis which lost the chance of surgery.Therefore,the main treatment for advanced gastric cancer includes chemotherapy,targeted therapy,immunotherapy.The purpose of this study is to review the transition and current patterns of drug therapy for advanced gastric cancer and to provide assistance for subsequent clinical studies in advanced gastric cancer.

Magnetic resonance imaging for diagnosis and neoadjuvant treatment evaluation in locally advanced rectal cancer:A pictorial review

High-resolution pelvic magnetic resonance imaging(MRI) is the primary method for staging rectal cancer.MRI is highly accurate in the primary staging of rectal cancer;however,it has not proven to be effective in restaging,especially in complete response evaluation after neoadjuvant therapy.Neoadjuvant chemoradiotherapy produces many changes in rectal tumors and on adjacent area,as a result,local tumor extent may not be accurately determined.However,adding diffusion-weighted sequences to the standard approach can improve diagnostic accuracy.In this pictorial review,an overview of the situation of MRI in the staging and re-staging of rectal cancer is exhibited as a pictorial assay.An experience-and literature-based discussion of limitations and difficulties in interpretation are also presented.

Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

Despite advances in the management of patients with locally advanced,non-metastatic rectal adenocarcinoma(LARC),prognosis remains largely unsatisfactory due to a high rate of distant relapse.In fact,currently available neoadjuvant protocols,represented by fluoropyrimidine-based chemo-radiotherapy(CT-RT)or short-course RT,together with improved surgical techniques,have largely reduced the risk of local relapse,with limited impact on distant recurrence.Available results of phaseⅢtrials with additional cytotoxic agents combined with standard CT-RT are disappointing,as no significant reduction in the risk of recurrence has been demonstrated.In order to improve the control of micrometastatic disease,integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach.In particular,the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models,and thusmay represent a suitable companion in the neoadjuvant treatment of LARC.Preliminary results of phase?Ⅰ-Ⅱclinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection:treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.

Professor YANG Yu-fei’s Experience on the Integrated Chinese and Western Medicine Treatment Strategy for Advanced Colorectal Cancer

Colorectal cancer is one of the common malignant tumors in China.It poses a serious threat to the national health of China.For advanced colorectal cancer, the main goal of treatment is to prolong survival and improve quality of life.It complements other advantages, showing good therapeutic results.However, how to grasp the timing of integrated Chinese and Western Medicine for the treatment of advanced colorectal cancer and use the integrated Chinese and Western Medicine treatment methods flexibly contains profound therapeutic art.Prof.YANG Yu-fei is an authoritative expert in the field of integrated Chinese and Western medicine for colorectal cancer.She is good at accurately grasping the timing of treatment of integrated Chinese and Western Medicine, and flexibly adjusts the treatment strategy according to the specific conditions.In this paper, we shared Professor YANG Yu-fei's strategy for treating advanced colorectal cancer with emphasis on integrated Chinese and Western Medicine and attached a typical case, with a view to provide reference for the treatment of advanced colorectal cancer with integrated Chinese and Western Medicine.

Analysis on the Clinical Therapeutic Effect of Hepatic Artery Chemoembolization in the Treatment of Advanced Liver Cancer

Objective:To analyze the clinical efficacy of hepatic artery chemoembolization in the treatment of advanced liver cancer.Methods:124 patients with advanced liver cancer admitted to our hospital from September 2019 to November 2020 were selected as the research subjects of this paper.The patients with advanced liver cancer were divided into experimental group and control group.The control group was treated with radiofrequency ablation alone,and the experimental group was administered hepatic arterial chemoembolization.The improvement in physical indicators and the incidence of adverse reactions between the two groups were compared.Results:The alpha-fetoprotein(AFP)index and serum total bilirubin(TBIL)index of the experimental group were lower than those of the control group,and the alanine aminotransferase(ALT)index was higher than that of the control group.There were differences in the comparison of liver function indices between the two groups which were statistically significant.After treatment,there were 3 cases of fever,4 cases of vomiting,8 cases of bone marrow transplantation,4 cases of abdominal pain,2 cases of proteinuria,and 1 case of diarrhea occurred in the experimental group;whereas there were 6 cases of fever,8 cases of vomiting,14 cases of bone marrow transplantation,7 cases of abdominal pain,5 cases of proteinuria,and 6 cases of diarrhea occurred in the control group.The difference in incidence of adverse reactions between patients after different treatment interventions was statistically significant.Analyzing the remission rate of tumor diseases in patients,the remission rate of the experimental group was higher than that of the control group,and the difference in the remission rate between the two groups of patients was statistically significant.Conclusion:The implementation of hepatic arterial chemoembolization for patients with advanced liver cancer can promote the improvement of the patient's short-term treatment efficacy,enhance the liver functions of the patient,reduce the incidence of adverse reactions,improve the efficiency of the patient's body rehabilitation,and enhance the quality of life of the patient after treatment.

Process of Decision-Making of Anti-Cancer Treatment in Elderly Patients with Advanced Lung Cancer

The aim of this study was to identify the decision-making process of anti-cancer treatment in elderly patients with advanced lung cancer. Semi-structured interviews were conducted with 17 patients aged 70 and above to collect data on their feelings and thoughts from the time of diagnosis till they made treatment decisions. The data was analyzed using the Modified Grounded Theory Approach that was modified by Prof. Yasuhito Kinoshita. We found the process to be composed of six categories. The results showed that elderly patients with advanced lung cancer were panicked over unavoidable death when informed of stage IV lung cancer and offered suggestions about anti-cancer treatment. However, trying to accept the situation where death is imminent, patients reconsidered having cancer in older age and recognized a desire to survive even in older age. This process diverged into two paths: one group of patients changed their ideas from radical to life-prolonging treatment by recognizing a desire to survive even in older age and then made anti-cancer treatment decisions by carefully choosing treatment that would allow to carry on their usual way of life;the other group of patients made treatment decisions by carefully choosing physicians to whom they could entrust their life in older age. These findings suggest that it is important for nurses to: 1) encourage patients to talk in order to have them think about what they have valued and want to value in the rest of their life;2) assess if patients prefer to decide on their own by carefully choosing treatment or entrust treatment decisions to physicians;and 3) offer support according to patients’ preferences.

Palliative Treatment of Locally Advanced Non Metastatic Lung Cancer

Introduction: To determine the proportion and the reasons which lead to palliative treatment in patients initially a candidate for concomitant chemoradiotherapy (CCRT). Methods: A retrospective study including patients followed for locally advanced lung cancer newly diagnosed from April 1, 2016, to 12/31/2017 in the radiotherapy department of the National Oncology Institute who received palliative treatment. Results: We collected 52 patients out of a total of 225 stage III patients (23%) followed by lung cancer candidates for CCRT who had undergone palliative treatment. The mean age in our series was 61.23 years [22 - 81] with 86% male. The majority of patients (71%) had Performance Status (PS) ≤ 2. Histological confirmation was obtained by pathological examination in all our patients. It was an adenocarcinoma (ADK) in 54% of cases;squamous cell carcinoma in 46% of cases. The reasons for palliative treatment were mainly due to dosimetric constraints: large tumor volume 22/52 (42%);the tumor location close to the bone marrow in 15 of 52 (29%) patients;and general Performance Status impairment (29%) in 15 of 52 patients. Palliative treatment consisted of palliative chemotherapy in 37 of 52 patients (71%), among whom 19 (51%) were stable after 2 months of chemotherapy, in palliative dose chest radiotherapy on the pulmonary parenchyma and/or mediastinum in 10 of 52 (19%) patients, and supportive care in 5 (10 %) patients. We observed 40/52 (77%) cases of stationary course, 04/52 (8%) cases of progress to metastases, and 08/52 (15%) deaths before radiotherapy. Conclusion: A large proportion of patients followed for locally advanced non-metastatic lung cancer are not eligible for curative treatment. The reasons for the palliative treatment of patients followed for lung cancer candidates for CCRT are variable but for a large proportion of patients due to the deterioration of their state of health during their diagnostic journey. Hence, there is the need to improve the early diagnosis and early management of patients with lung cancer to avoid delayed care.

Role of radiation therapy in neoadjuvant era in patients with locally advanced rectal cancer

Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.

Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

AIM:To assess the clinical diagnostic value of functional imaging,combining quantitative parameters of apparent diffusion coefficient(ADC) and standardized uptake value(SUV)max,before and after chemo-radiation therapy,in prediction of tumor response of patients with rectal cancer,related to tumor regression grade at histology.METHODS:A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study.All patients underwent a whole body ^(18)FDG positron emission tomography(PET)/computed tomography(CT) scan and a pelvic magnetic resonance(MR)examination including diffusion weighted(DW) imaging for staging(PET1,RM1) and after completion(6.6 wk)of neoadjuvant treatment(PET2,RM2).Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings.The MR scanning,performed on 1.5 T magnet(Philips,Achieva),included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm^2/s.On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2.The percentage decrease of SUVmax(△SUV) and ADC(△ADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade(Mandard's criteria;TRG1 = complete regression,TRG5 = no regression).RESULTS:After completion of therapy,all the patients were submitted to surgery.According to the Mandard's criteria,22 tumors showed complete(TRG1) or subtotal regression(TRG2) and were classified as responders;9tumors were classified as non responders(TRG3,4 and5).Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2(P < 0.001),whereas the mean ADC values was lower in RM1 than RM2(P < 0.001),with a △SUV and △ADC respectively of 60.2%and 66.8%.The best predictors for TRG response were SUV2(threshold of4.4) and ADC2(1.29 × 10^(-3) mm^2/s) with high sensitivity and specificity.Combining in a single analysis both the obtained median value,the positive predictive value,in predicting the different group category response in related to TRG system,presented R^2 of 0.95.CONCLUSION:The functional imaging combining ADC and SUVmax in a single analysis permits to detect changes in cellular tissue structures useful for the assessment of tumour response after the neoadjuvant therapy in rectal cancer,increasing the sensitivity in correct depiction of treatment response than either method alone.

Contemporary management of locally advanced rectal cancer:Resolving issues, controversies and shifting paradigms

Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy（CRT） followed by total mesorectal excision（TME） reaches a plateau, the need for alternative strategies in locally advanced rectal cancer（LARC） has grown in relevance. Several novel strategies have been conceptualized to address this issue, including： 1） neoadjuvant induction and consolidation chemotherapy before CRT; 2） neoadjuvant chemotherapy alone to avoid the sequelae of radiation; and 3） nonoperative management for patients who achieved pathological or clinical complete response after CRT. This article explores the issues, recent advances and paradigm shifts in the management of LARC and emphasizes the need for a personalized treatment plan for each patient based on tumor stage, location, gene expression and quality of life.

New standard in locally advanced rectal cancer

In the following review we intend to ascertain the optimal neoadjuvant therapy inpatients with locally advanced rectal cancer. In 2004, a study revealed thatchemoradiotherapy (CRT) resulted in better local control when performedpreoperatively rather than postoperatively, thus neoadjuvant treatment wasestablished as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant differencebetween concomitant CRT over 5 wk vs short-course radiotherapy (RT).Therefore, both were established as standard neoadjuvant treatments. Later, theStockholm III study demonstrated that short-course RT had a higher completepathological response than long-course RT. It also showed that a delay betweenRT and surgery presented fewer complications. This opened a window of time toprovide an early and effective systemic treatment to prevent distant metastases.Studies show that short-course RT plus oxaliplatin-based chemotherapy couldachieve this. When comparing this total neoadjuvant treatment (TNT) vsconcomitant CRT, the former showed greater complete pathological response andlower acute toxicity. Studies presented during 2020 have also shown the benefitsof TNT in terms of complete pathological response, as well as disease andmetastasis-free survival. Our review suggests that probably TNT should be thenew standard treatment for these patients. However, we will have to wait for thefull text publications of these studies to confirm this statement.

S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer(AGC). METHODS: We extracted reported endpoints, including overall survival(OS), progression-free survival(PFS), time-to-treatment failure(TTF), objective response rate(ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values.RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR(RR = 1.300; 95%CI: 1.028-1.645); OS(HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF(HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia(RR = 0.225; P = 0.000) and stomatitis(RR = 0.230; P = 0.032). OS, PFS and TTFwere prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR(RR = 1.454; P = 0.029), OS(HR = 0.895; P = 0.041) and TTF(HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil(5-FU)-based chemotherapy. The incidence of leukopenia(RR = 0.584; P = 0.002) and stomatitis(RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens. CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use.

Advances in TCM Treatment of Gastric Cancer and Studies on the Apoptosis

The significance of apoptosis in gastric cancer is now widely recognized, and the induction of apoptosis as a new approach to treat gastric cancer has aroused great interest. In recent years, studies on certain TCM drugs for treating gastric cancer and for inducing apoptosis have brought about great attention both at home and abroad. The following is a summary made in this aspect.

New advances in targeted gastric cancer treatment

Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

Pancreatic cancer: Advances in treatment

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing.While patients with pancreatic cancer have traditionally faced a dismal prognosis,over the past several years various advances in diagnosis and treatment have begun to positively impact this disease.Identification of effective combinations of existing chemotherapeutic agents,such as the FOLFIRINOX and the gemcitabine+nab-paclitaxel regimen,has improved survival for selected patients although concerns regarding their toxicity profiles remain.A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions,such as pancreatic intraepithelial neoplasias,intraductal papillary mucinous neoplasms,and cystic neoplasms.Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management.Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors,and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality.Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy.Furthermore,pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes.Lastly,a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents.

Locally advanced rectal cancer:The importance of a multidisciplinary approach

Rectal cancer accounts for a relevant part of colorectal cancer cases,with a mortality of 4-10/100000 per year.The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients.In the last two decades,new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival.Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates.The employment of neoadjuvant treatment,delivered before surgery,also achieved an improved local control and an increasedsphincter preservation rate in low-lying tumors,with an acceptable acute and late toxicity.This review describes the multidisciplinary management of rectal cancer,focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.