Era Of Chemotherapy Research Articles

Potential Prognostic and Predictive Role of Monocyte and Lymphocyte Counts on Presentation in Patients Diagnosed With Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma. Nearly 40% of patients will die of relapsed disease despite the use of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. Many prognostic markers established in the chemotherapy era are no longer valid in the rituximab era. We aim to identify whether we can add absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte-to-monocyte ratio (LMR) as new prognostic factors for DLBCL treated with R-CHOP. We also aim to find whether a correlation exists between these variables and the revised International Prognostic Index (R-IPI) score. This is an observational retrospective study done from 2005 to 2015 in Rafic Hariri University Hospital (RHUH), Lebanon, on 42 patients treated with R-CHOP. Patients' data were obtained from medical records. We used receiver operating characteristic (ROC) curve for establishing cutoff values. The chi-square test was used to analyze associations between variables. Patients were followed for a median of 42 months (24-96 months). Patients with LMR < 2.53 had a significantly worse outcome than those with LMR ≥ 2.53 (p< 0.0001). This was also true for patients with ALC < 1.47 × 109/L (p= 0.0163) and AMC > 0.603 × 109/L (p= 0.0053). LMR was also able to risk-stratify patients within each R-IPI category into high- and low-risk patients. ALC, AMC, and LMR, surrogate markers of the host immune system and tumor microenvironment, have prognostic significance in DLBCL patients treated with R-CHOP.

The role of local treatment including pancreatectomy for pancreatic ductal adenocarcinoma patients with isolated synchronous liver metastasis: Propensity score-matched analyses.

In an era of more effective chemotherapy for pancreatic ductal adenocarcinoma (PDAC), the paradigm of local treatment is changing. However, the efficacy of local treatment in patients with isolated liver metastasis remains unclear. Therefore, we aimed to evaluate the effectiveness of pancreatectomy ± local treatment for metastasis (cytoreductive surgery) in PDAC patients with isolated synchronous liver metastasis. In total, 239 patients with isolated liver metastasis were extracted from Seoul National University Hospital (SNUH). For comparison, another 12 637 patients were extracted from the National Cancer Database (NCDB). Propensity score matching was performed to minimize confounding in both cohorts. Survival analyses stratified by the treatment delivered were performed using Kaplan-Meier estimates and log-rank tests. In the SNUH cohort, the median (interquartile range) survival was 20.5 (13.0-42.0) months for patients who underwent cytoreductive surgery plus chemotherapy versus 12.0 (10.0-18.0) months for those who received chemotherapy alone (P< .001). With the NCDB cohort, the median (interquartile range) survival was 15.6 (8.9-31.2) months for patients who underwent cytoreductive surgery plus chemotherapy versus 7.4 (3.4-13.2) months for those who received chemotherapy alone (P < .001). Patients with isolated synchronous liver metastasis should be considered for cytoreductive surgery in addition to effective chemotherapy.

Impact of D2 Gastrectomy for Locally Advanced Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

Gastrectomy with D2 dissection has been established as the standard procedure for locally advanced gastric cancer in the era of surgery alone. However, no consideration has been given to the efficacy of dissection in the era of effective adjuvant chemotherapy. This study included 1298 advanced gastric cancer patients, consisting of 725 cases treated between January 2000 and December 2006 (Former group), and 573 cases treated between January 2007 and July 2015 (Latter group). Clinicopathological data were collected, survival and the therapeutic value index were determined. The background characteristics were well balanced, except for age, tumor location, and intraoperative blood loss. The Latter group showed the following characteristics: an older population (p < 0.001), a frequent upper location (p = 0.008), and less blood loss (p < 0.001). Adjuvant chemotherapy was administered to 75.2% of the Latter group and was 9.4% in the Former group. The 5-year overall survival rate of the Latter group was 75.7% (95% confidence interval: 71.7-79.1), significantly better than that of the Former group (70.0%, 95% confidence interval: 66.5-73.2) (p = 0.025). Improvement in the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between these two groups was 1.09 at the D1 station and 1.19 at the D2 station. The therapeutic value index was improved in all nodal stations by S-1 adjuvant chemotherapy, regardless of whether the D1 or D2 nodes were involved. D2 gastrectomy would be still important for locally advanced gastric cancer in the era of effective adjuvant chemotherapy.

Exploring optimal therapeutic management of STAGE IA PDAC in the era of neoadjuvant chemotherapy.

712 Background: Neoadjuvant chemotherapy (NAT) is currently recommended for non-metastatic pancreatic ductal adenocarcinoma (PDAC). Data on the optimal NAT duration and the proper post-surgical chemotherapy (PSC) are lacking, especially for patients (pts) who yielded a pathological stage IA. Methods: We retrospectively analyzed the outcome of PDAC pts resected between 2015 and 2020 at our institution after NAT yielding a pathologic stage of PDAC ypT1N0. Pts were analyzed basing on NAT duration (aim 1) and PSC indication (yes/no) and type (aim 2). The primary endpoint was median event-free survival (EFS) for aim 1 and median disease free-survival (DFS) for aim 2. As per secondary endpoints, overall survival (OS) and the prognostic role of clinical and pathological variables was assessed (baseline CA19.9 level; pre-operative Ca19.9 level, basal vascular involvement, grading, perineural invasion, R1 resection). Results: During the study period a total of 756 pts were resected, 363 (48%) after NAT. Of them, 72 pts (20%) achieved a pathological ypT1N0 (ypIA). Among this group 16 pts (22%) showed a T1a-T1b, 62 pts (86%) had a G1/G2 tumor, 60 pts (83%) had a R0, 36 pts (50%) had a perineural invasion and 33 (46%) had a tumor regression grade marked or completed. For aim 1 we compared 34 pts (47%) treated with NAT for not more than 4 months (Group A1) and 38 pts (53%) treated for at least 4 months (Group B1). Baseline, biochemical and radiological variables were similar between the 2 groups. No statistical difference was found in EFS (Group A1: median 46 months/ Group B1: median not reached). For aim 2 we compared 10 pts (14%) who received the same chemotherapy regimen in NAT and PSC (Group A2), 35 pts (49%) who received a different chemotherapy regimen in NAT and PSC (Group B2) and 27 (14%) pts who did not receive any PSC (Group C2). PSC were gemcitabine/nab-paclitaxel (10%) and mFOLFIRINOX (90%) in group A2, whereas gemcitabine/nab-paclitaxel (17%), mFOLFIRINOX (3%), gemcitabine (51.5%), capecitabine (17%), gemcitabine/capecitabine (8.5%), PEXG (3%) in group B2. DFS were 24 months for group B2, whereas median was not reached for group A2 e C2 (p=0.006). No statistical difference was found in OS among the groups. At multivariate analysis only grading (G3) emerged as independent factor for poor prognosis. Conclusions: In ypIA pts NAT duration and or type seem to be unrelated to the outcome. PSC performed with alternative and depotentiated chemotherapy as compared to NAT, seem to be related to a higher rate of disease recurrence. Poor differentiated/G3 tumors is confirmed as independent risk factor for poor survival in this population.

Az onkokardiológia kialakulása

In our days, the worldwide leading cause of mortality is cardiovascular, and the second place is held by cancer diseases. Actually, we achieved a significant breakthrough in cancer treatment through multi-disciplinary cooperation but parallel there were emerging cardiac side effects. Several hundred years earlier all cancer patients were considered uncurable, and they were labelled this way through many centuries. Some people are thinking the same way even in our days. The first therapeutic initiatives were surgical operations aiming to remove cancer tissues. These therapeutic approach flourished in the surgeons’ century by spreading of general anaesthesia. At the end of the 19th century, a new diagnostic and therapeutic approach used the X-ray technique which spread fast throughout the world. In the middle of the 20th century, scientist started to investigate the chemical weapons of warfare and discovered, that these lessened the progression of some cancer types. Thanks to these discoveries, there was introduced the first anti-cancer drug aminoptein that opened the era of chemotherapy. However, after a few years, it was realized that some patients treated by pharmaceuticals of the antraciklin groups developed heart failure. This phenomenon instigated more scientists to investigate heart-related side effects. Later, there were observed similar side effects as developing high blood pressure and ECG anomalies in patients treated with further chemicals such as HER-2 blocking herceptin and multi-kinase inhibitors. These researcher outcomes were more and more noticed in the practical cardiology in patients treated previously by chemotherapy. Finally, in 2016 the European Society of Cardiology issued the first guideline about the side effects of cancer chemotherapy patients, which started the era of on-cardiology. Since 2016, the once-cardiology become a new medical discipline that concerns the prevention of complications, and the recognition and treatment of heart-related side effects. In the same year was founded the Hungarian Onko-cardiology Society which is translating, spreading and exposing the actual guidelines and holds annual conferences for postgraduate training.

Colorectal Liver Metastases: A Literature Review of Viable Surgical Options with a Special Focus on Microwave Liver Thermal Ablation and Mini-Invasive Approach.

Colorectal cancer (CRC) is the third most common tumor worldwide and it is characterized in 20-30% of cases by liver involvement, which strongly affects the long-term patient outcome. There are many available therapies for liver colorectal metastases (CRLMs); the current standard of care is represented by liver resection, and when feasible, associated with systemic chemotherapy. Microwave thermal ablation (MWA) is a viable option in unresectable patients or to achieve treatment with a parenchymal spearing approach. A literature review was performed for studies published between January 2000 and July 2022 through a database search using PUBMED/Medline and the Cochrane Collaboration Library with the following MeSH search terms and keywords: microwave, ablation, liver metastases, colorectal neoplasm, and colon liver rectal metastases. The recurrence rate and overall patients' survival were evaluated, showing that laparoscopic MWA is safe and effective to treat CRLMs when resection is not feasible, or a major hepatectomy in fragile patients is necessary. Considering the low morbidity of this procedure, it is a viable option to treat patients with recurrent diseases in the era of effective chemotherapy and multimodal treatments.

Why people die of active tuberculosis in the era of effective chemotherapy in Southern Ethiopia: A qualitative study

BackgroundHigh TB mortality is increasingly understood as an indicator of different problems in the health system and community. Limited awareness of TB in the community, restricted accessibility and/or quality of health services can hamper survival. Exploration and analysis of death among TB patients can lead to a clearer and specific understanding of why the deaths happened and where interventions are likely to make a difference in a specific context. ObjectiveThe study aimed to assess why people die of active tuberculosis in the era of effective chemotherapy. MethodsThe study was conducted from October to December 2020 in Arba Minch Health and Demographic Surveillance System (AM-HDSS) by applying phenomenological study design. A total of 27 family members of people who had died of TB, 9 health extension workers (HEW) and 8 health care professionals working in TB clinics were participated in open in-depth interview. A total of 130 individuals participated in 16 focus group discussion which composed of patient survived from TB, religious leader, health development army (HAD) and HEWs. Adequacy of information (saturation) was considered as an adequate sample size to create the intended qualitative product. All the interviews and FGD were tape recorded and recordings were transcribed immediately. ATLAS TI 9 software was used to analyse and process qualitative data. From data set codes were created then by identifying pattern among them themes were created. Then, generated themes were compared and some of them were split, combined, discarded and new ones created after returning to data set. Finally, themes were defined and a concise and easily understandable name was given for each theme. ResultLuck of sufficient knowledge about TB was considered to be a reason for cause of death. Most of the time, TB patients underestimate and ignore when the symptoms first emerge and will not relate it with any diseases. The low level of community awareness about the cause, transmission, treatment and prevention highly contributed to increased transmission rate and death due to TB. The study identified misconceptions in the community; they prefer traditional medicine to the scientific way. First, they try different herbal medicine to get relief from their illness. At the end, if the disease is getting worse, they visit health facilities. Participants mentioned high transportation cost, poor health seeking behaviours, inadequate food consumption and lack of TB awareness as reasons for low treatment adherence. The health facilities were inaccessible for the community. Most of them indicated that health facilities were too far to reach. In some health institution, right amount and combination of medication were not delivery on time and Diagnostic facilities for TB were reported to be inadequate. ConclusionPoor treatment adherence, lack of TB awareness, stigma, inadequate food consumption, poor health care seeking behaviour and inaccessibility of health facility were identified as major reasons for death. To prevent death of TB patients all sectors such as education, health, and agriculture should work to address health education, infrastructures, nutritional supplementation needs of TB patients, caregivers and the community as a whole.

Basic principles of contemporary chemotherapy of malignant gliomas of the brain

The modern view on the place of antiblastic chemotherapy in clinical neuro-oncology based on NCCN 2021 clinical guidelines (The National Comprehensive Cancer Network), EANO recommendations (The European Association for Neuro-Oncology), cIMPACT-NOW (The Consortium for Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) and many years of experience of the department of adjuvant treatment for the central nervous system tumors of the State Institution "Romodanov Neurosurgery Institute, Ukraine" is presented and the basic principles of its application in the complex treatment of malignant gliomas of the brain are substantiated. Malignant gliomas are a heterogeneous group of the most numerous primary tumors of the central nervous system, differing in both the grade of malignancy and the prognosis of the disease. The latest WHO tumors classification 2021 defines this group of tumors as "diffuse gliomas" of the brain, that is, the term itself indicates infiltrative nature of their growth, that limits the possibility of surgical removal and requires a multimodal approach to their treatment in order to maximize the reduction of tumor tissue. The new era of chemotherapy in neuro-oncology, as well as in general oncology, began with the study of the molecular profile of tumors, which is important both for predicting the course of the disease and for choosing tactics of chemotherapeutic treatment of malignant gliomas. It’s enough to give the following example: in the absence of IDH gene mutation and co-deletion of chromosome 1p/19q loci in grade 2 of anaplasia diffuse gliomas, the prognosis of the disease does not differ from that in glioblastoma multiforme. For the same reason, in modern neuro-oncology, the designation of molecular genetic markers in malignant gliomas is essential for the personification of the treatment of pathology is essential to personalize the treatment of this pathology.

Radiotherapy-triggered prodrug activation: A new era in precise chemotherapy

A major goal of cancer therapy is developing chemotherapy strategies that are accurate and efficient without being highly toxic. Recently, Bradley etal.1 and Liu etal.2 developed radioresponsive prodrugs, enabling site-directed, radiotherapy-triggered, and precise chemotherapy, which displays synergistic efficacy and avoids the serious side effects of conventional treatment approaches.

Relationship between the number of lymph nodes dissected and prognosis in muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy.

Many studies have shown a good prognostic association with a large number of lymph node dissections. However, most of these studies did not include patients who have received neoadjuvant chemotherapy. The purpose of this study was to verify the relationship between survival outcomes and the number of lymph nodes removed during radical cystectomy in patients with muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy. This retrospective study considered patients who were diagnosed with clinical ≥T2N0M0 muscle-invasive bladder cancer and treated with radical cystectomy at the Nagoya University Hospital and affiliated hospitals from January 2004 to December 2019. We excluded patients who had a history of upper tract urothelial cancer or non-urothelial carcinoma. The association between prognosis and the number of lymph nodes removed was investigated. We retrospectively enrolled a total of 477 patients. The mean number of lymph nodes dissected was 14. Two hundred and twenty-six patients (47.4%) received neoadjuvant chemotherapy. More extensive lymphadenectomy (≥15 lymph nodes) correlated with better 5-year overall survival across all patients (68% vs. 57%, p = 0.01). In patients who received neoadjuvant chemotherapy, there was no difference in overall survival according to the number of dissected lymph nodes (66% vs. 71%, p = 0.433). In patients who did not receive neoadjuvant chemotherapy, ≥15 lymph nodes dissected was associated with significantly better overall survival (70.3% vs. 46.9%, p < 0.01). No association between more aggressive lymph node dissection and prognosis was found in patients who underwent neoadjuvant chemotherapy. Conversely, extended lymph node dissection is desirable for patients who have not received neoadjuvant chemotherapy.

The role of adjuvant EGFR-TKIs for completely resected EGFR-mutant non-small cell lung cancer in an era of chemotherapy: An updated systematic review and meta-analysis.

e20501 Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Previous meta-analyses explored the possible benefit of adjuvant EGFR-TKIs compared to chemotherapy for patients with completely resected non-small-cell lung cancer (NSCLC). In this meta-analysis, we present the most up-to-date efficacy and safety comparison of adjuvant tyrosine kinase inhibitors (TKIs) and adjuvant chemotherapy for those patients. Methods: We conducted a systematic review using PubMed, Scopus, and Cochrane CENTRAL databases up to January 2022. All randomized clinical trials (RCTs) comparing TKIs as a monotherapy or as a combination with chemotherapy against placebo or chemotherapy in a completely resected EGFR-mutant NSCLC adjuvant setting were included. Studies with ten or fewer patients in either arms were excluded. The primary outcomes were disease-free survival (DFS) and overall survival (OS) with a reported hazard ratio (HR), while adverse events (AEs) were the secondary outcome. Random or fixed-effects meta-analyses were performed based on heterogeneity. Results: A total of eight eligible RCTs of 1752 EGFR-mutant completely resected NSCLC patients were included in this meta-analysis. Six studies involved EGFR-TKIs as monotherapy (n = 1653) whereas two studies involved a combination of EGFR-TKIs with chemotherapy (n = 99). The DFS in the TKIs monotherapy group was significantly improved when compared to chemotherapy (HR = 0.48, 95% CI: 0.29-0.80; p = 0.005), but insignificantly when compared to placebo (HR = 0.34, 95% CI: 0.12-1.02; p = 0.06), with an overall HR of 0.42 (95% CI: 0.25-0.71; p = 0.001), while the OS difference was not of statistical significance (HR = 0.91, 95% CI: 0.70-1.17; p = 0.44). No difference in DFS was found when comparing between the Exon-19 deletion and L858R mutation types (p = 0.37). No subgroup difference in DFS was found as well between TKIs monotherapy and combination therapy when both were compared to chemotherapy (p = 0.45). Grade ≥ 3 AEs were significantly less common in the TKIs group compared to chemotherapy (OR = 0.12, 95% CI:0.06-0.24; p &lt; 0.001). Grade 3/4 rash, diarrhea, and infections were more common in the TKIs group (3.6% vs 0.0%, 2.1% vs 0.7%, and 1.7% vs 0.0%, respectively), while chemotherapy had a higher hematological involvement in terms of grade 3/4 neutropenia, leukopenia, and anemia (44.9% vs 0.2%, 25.2% vs 0.0%, and 5.8% vs 0.1%, respectively). Conclusions: The use of TKIs as adjuvant therapy in completely resected EGFR-mutant NSCLC significantly improves the DFS compared to chemotherapy, regardless of the mutation type, and with a better AEs profile as well, but does not affect the OS. Furthermore, The combination of TKIs and chemotherapy did not demonstrate a difference in DFS when compared to TKIs alone, however, prospective trials comparing both arms are needed to confirm this finding.

The Influence of c-Kit and NRAS Mutation on Patients’ Survival in Metastatic Melanoma Receiving Immune Checkpoint Inhibitors and Chemotherapy

The high metastasis and mortality rates of melanoma in the era of chemotherapy have decreased significantly over the last 10 years. The success is owed largely to the introduction of targeted therapy of oncogenes and immunotherapies, such as checkpoint inhibitors. The aim of the present retrospective, monocentric study is to investigate the impact of chemotherapy or immunotherapy in 550 patients with metastatic melanoma between the years of 2010 and 2019, looking at overall survival while considering BRAF/NRAS/c-KIT mutation status. A total of 17 patients were found to have a c-KIT mutation in exon 11, 13 or 17, including 58.3% with acral lentiginous melanoma, with 53% localized primarily in the lower limbs. In 13.3% of the 231 NRAS-mutated melanomas, primary tumor location was found to be in UV-exposed skin such as on the head and neck, thus about 50% lower than in the 302 patients with wild-type (BRAF-/NRAS-/cKIT-negative) melanoma. Patients with NRAS-mutated melanomas had a significantly lower probability of survival compared to patients with wild-type melanomas, irrespective of the recommendations of the clinical guideline on drug therapy for metastatic melanoma that have been in force since 2010. In contrast to patients with wild-type melanoma who showed a higher probability of survival receiving immune checkpoint inhibitors, the overall survival of patients with NRAS-mutated metastatic melanoma was not more favorable after therapy with immune checkpoint inhibitors compared to chemotherapy treatment.

Impact of TKI combination therapy and MRD negativity on outcomes in Philadelphia chromosome-positive ALL: A retrospective, single-center experience.

e19052 Background: Presence of the Philadelphia chromosome (Ph+) in newly diagnosed B-cell acute lymphoblastic leukemia (ALL) conveys high-risk disease and a poor prognosis. Hematopoietic stem cell transplant (HSCT) following induction and achievement of remission remains the standard of care. In the era of TKIs targeting BCR-ABL1 in addition to newer combination strategies, the impact of HSCT in the first complete remission (CR) remains unclear, particularly in the context of measurable residual disease (MRD) negativity. We present the outcomes of Ph+ B-ALL patients with and without HSCT, stratified with respect to MRD negativity. Methods: We identified 32 patients with Ph+ B-cell ALL from January 2015 to January 2021 at our institution who were treated with TKIs and received HSCT with evaluable MRD prior to transplant. Baseline patient demographics were obtained, including labs, performance status at diagnosis, comorbidities, molecular profiling by NGS, doses of induction, toxicities, response, MRD analysis by PCR, HCT-CI scores, and HSCT outcomes. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: Of the 25 patients who underwent HSCT, the median age was 46 years and 48.0% were male. TKIs in combination with high-intensity regimens were given in 88.0% of patients at induction. There were no deaths within 60 days following induction. Twenty (80.0%) patients achieved CR or CRi, and of those, 56% were MRD-negative by the time of HSCT. At a median follow-up time of 4.74 years, the OS of patients that achieved CR following induction and HSCT was not reached, and there were no significant differences between the two groups (p = .1326). We then compared the 14 MRD-negative patients undergoing HSCT to 7 MRD-negative patients who did not undergo transplant aged ≤65 years with ECOG ≤2. There was no difference in age (p = .5353), ECOG score (p = .6364), or Charlson Comorbidity Index score (p = .7018) between the two groups. The median OS in the MRD-negative HSCT group was not reached and the median OS in the MRD-negative non-HSCT was 5.45 years (p = .0210). Conclusions: In the era of combination chemotherapy with TKIs, MRD positivity at the time of allogenic HSCT does not appear to impact survival at 5 years in this small retrospective cohort. Post-transplant TKI maintenance may abrogate MRD implications at the time of HSCT. Our findings demonstrate that Ph+ ALL patients benefit from HSCT when candidates, regardless of MRD status, as those undergoing HSCT demonstrated a statistically superior survival. HSCT appears to remain the standard of care despite newer combination strategies and MRD-driven treatment.

Can Surgical Resection of Metastatic Lesions Be Beneficial to Pancreatic Ductal Adenocarcinoma Patients with Isolated Lung Metastasis?

Simple SummaryWith the development of chemotherapy, studies have been conducted on the possibility of conversion surgery in metastatic pancreatic ductal adenocarcinoma (PDAC) patients. In addition, studies with large-scale public data have reported that patients with isolated lung metastasis have a good prognosis and can benefit from survival through surgical treatment. Our study aims to evaluate the effect of metastatectomy and prognostic factors in PDAC patients with isolated lung metastasis by analyzing the data from 1342 patients in our institution. We showed that PDAC patients with isolated lung metastasis who underwent metastatectomy seemed to have better survival when compared with patients who underwent only chemotherapy or supportive care. In addition, we performed the analysis using the National Cancer Database for external validation purposes and found consistent results compared to our analysis. Our findings suggest that PDAC patients with isolated lung metastasis should be considered for multimodal therapy with chemotherapy and surgical treatment.In the era of effective chemotherapy on pancreatic ductal adenocarcinoma (PDAC) with distant metastasis, data on the effects of metastatectomy are lacking. So, we investigated the effect of metastatectomy on survival after metastasis in PDAC patients with isolated lung metastasis. This retrospective study analyzed 1342 patients who were histologically diagnosed with PDAC with distant metastasis from January 2007 to December 2018, of which 83 patients had isolated pulmonary metastasis. Additionally, 4263 patients were extracted from the National Cancer Database (NCDB) and analyzed. Log-rank test and Kaplan−Meier survival analysis were used to analyze survival after metastasis. The five-year survival rate was significantly higher in patients who underwent pulmonary metastatectomy than in those who received only chemotherapy or supportive treatment (60.6% vs. 6.2% vs. 0.0%, p < 0.001). A similar trend was observed in the NCDB (two-year survival rate, 27.4% vs. 15.8% vs. 4.7%, p < 0.001). In the multivariate analysis, lung lesion multiplicity (hazard ratio (HR) = 2.004, p = 0.017), metastatectomy (HR = 0.278, p = 0.036), chemotherapy (HR = 0.434, p = 0.024), and chemotherapy cycles (HR = 0.300, p < 0.001) had significant effects on survival. Metastatectomy with primary pancreatic lesions is recommended with effective chemotherapy in PDAC patients with isolated lung metastasis.

Allogeneic Hematopoietic Stem Cell Transplantation for Adult Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia in Second Complete Remission

Even in the era of high-intensity chemotherapy, disease recurrence remains a major cause of treatment failure in adult patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative B-ALL). For patients who achieved second complete remission (CR2) with salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be the best curative treatment. However, limited data are available on the outcomes of allo-HSCT for adult Ph-negative B-ALL in CR2 in the high-intensity chemotherapy era. We evaluated the transplantation outcomes of adult patients with Ph-negative B-ALL in CR2 compared with those in CR1. We also clarified the prognostic factors among adult allo-HSCT recipients with Ph-negative B-ALL in CR2. We conducted a nationwide retrospective study using the data form Japanese transplant registry database. Patients aged ≥16 years and underwent their first allo-HSCT between 2003 and 2017 were included. The 3-year overall survival (OS) rate of the patients in CR2 (n=382) was significantly lower than that in first complete remission (n=1375) (51.8% versus 68.1%; P < .001), accompanied by a higher relapse rate (34.2% versus 17.6% at 3 years; P < .001). In a multivariate analysis among CR2 patients, time from diagnosis to allo-HSCT (≤2 years) was a significant factor for OS (hazard ratio [HR] 1.87; P < .001) and relapse (HR=1.88; P < .001), whereas age at allo-HSCT (≥30 years) was a significant factor for OS (HR=2.10, P < .001) and nonrelapse mortality (HR=2.68; P < .001). By assigning a score of 1 to each factor, the 3-year OS rate of CR2 patients significantly stratified: 70.7% in patients with score 0, 56.4% with score 1, and 28.4% with score 2 (P < .001). The survival outcomes of allo-HSCT in adult Ph-negative B-ALL patients in CR2 were inferior to those in CR1 in the high-intensity chemotherapy era, mainly because of the higher relapse rate. Among the CR2 patients, the short time between diagnosis and allo-HSCT was a significant risk factor for disease recurrence and overall mortality. Better disease control with novel treatment strategies may be needed for early relapse. In addition, the nonrelapse mortality rate in patients over 30 years of age was particularly high among CR2 patients, suggesting the need for improved supportive care for these patients. Further studies are warranted on the outcomes of allo-HSCT after achieving CR2 with novel drugs, such as inotuzumab ozogamicin and blinatumomab.

Update analysis: Clinical outcomes following regionalization of gastric cancer care in a U.S. integrated health care system.

265 Background: The role of laparoscopic gastrectomy and D2 lymphadenectomy is not yet fully defined in patients treated with modern perioperative chemotherapy. In 2016, Kaiser Permanente Northern California regionalized gastric cancer care, introducing a regional comprehensive multidisciplinary care team, standardizing staging and chemotherapy, and implementing laparoscopic gastrectomy and D2 lymphadenectomy for eligible patients with curative-intent surgery. We previously reported a retrospective cohort study comparing treatments and outcomes before and after regionalization, including 2-year overall survival. Here we present updated 3-year overall survival. Methods: As we described previously ( https://ascopubs.org/doi/full/10.1200/JCO.21.00480 ), the study included all 1429 patients with gastric cancer diagnosed during January 2010 to May 2018, of whom 942 were pre-regionalization, and 487 were post. Of the 1429, 650 had Stage I-III disease, and 394 patients underwent curative intent gastrectomy. 34.9% received neoadjuvant chemotherapy, and 18.4 % of patients received laparoscopic gastrectomy in the pre-regionalization period. In contrast, 66.2% received neoadjuvant chemotherapy, and 91.8% received laparoscopic gastrectomy with D 2 lymphadenectomy in the post regionalization period (p &lt; 0.0001). Lymph node metastasis was noted in 50.7% and 45.1% pre- and post-regionalization periods, respectively (p = 0.29). Survival was analyzed using Kaplan-Meier analysis with entry on the diagnosis date, the outcome on the death date, and censoring on disenrollment or the end of the study. In this updated analysis, the end of the study was increased by one year to December 31, 2019. Results: The statistical analysis showed no difference in patients’ selection for surgery between the pre-and post-regionalization period and no change in the rate of surgical complications. At three years, overall survival among Stage I-III patients who received surgery was 66.0% in the pre-regionalization cohort and 83.0% in the post-regionalization cohort (p &lt; 0.002), a more significant difference than was observed at two years. Conclusions: The utilization of laparoscopic surgery and radical D2 lymphadenectomy in the era of perioperative chemotherapy continues to demonstrate improved postoperative overall disease survival.[Table: see text]

Trends in long-term survival after liver resection for gastric cancer liver metastasis: Analysis of a single-center experience over 28 years.

290 Background: While systemic chemotherapy for gastric cancer has evolved significantly in the last decade, the role of surgery for liver metastasis remained controversial. The aims of this study were to examine the trend in outcomes of patients with gastric cancer liver metastasis (GCLM) undergoing resection at our center, and to define the optimal selection criteria for resection. Methods: One hundred and twenty-two consecutive patients who underwent liver resection for GCLMs with curative intent at our institution from 1993 through 2021 were included. The patients were grouped into 2 eras: era I, 1993 to 2010; era II, 2011 to 2021. Our criteria for liver resection included absence of extrahepatic disease, and the limited number of liver metastasis (often 3 or less). Median follow-up was 34 months for all and 71 months for the survivors. Results: There were 63 patients in era I and 59 in era II. The patients in era II received chemotherapy prior to liver resection more often (68% vs 41%, p = 0.004), and their primary tumor was less advanced (T3/4; 66% vs 85%, p = 0.021) with less regional lymph node metastasis (median No. of positive nodes; 4 vs 1, p = 0.034) compared to those in ear I. Median and 5-year disease-specific survival (DSS) were better in era II (not reached, 55%) than in era I (35 months, 35%, p = 0.025). In the multivariate analysis for the entire cohort, elevated CEA (&gt; 50 ng/ml), primary T4, and primary at the proximal stomach emerged as independent factors associated with shorter DSS. Number of these risk factors are highly predictive for long-term survival; among the patients without or with a single factor alone, 5-year DSS was 50%, whereas none of those with multiple risk factors survived beyond 5 years ( p&lt; 0.0001). Conclusions: Long-term outcomes for patients with oligo-GCLM has improved in the modern chemotherapy era. Liver resection should be considered unless they carry multiple risk factors.

Episcleral Iodine-125 radioactive plaque brachytherapy as a salvage treatment for retinoblastoma in the era of intraarterial chemotherapy.

Retinoblastoma shows high rates of recurrence after initial chemotherapy (systemic or intraarterial). Our aim was to evaluate the effectiveness of iodine-125 radioactive plaque brachytherapy as a salvage treatment with globe-preserving attributes after initial chemotherapy in patients with intraocular retinoblastoma. The effect of brachytherapy was investigated retrospectively in 17 eyes of 17 patients who were followed up due to retinoblastoma between May 2012 and June 2018 and who received iodine-125 radioactive plaque brachytherapy as a salvage treatment after systemic or intra-arterial chemotherapy. The regression, ocular toxicity, and enucleation rates were evaluated at the end of the follow-up period. The tumor locations were post equator, macular, anterior to the equator, and peripapillary in 5, 3, 7, and 2 patients, respectively. Regression was initially and rapidly observed in 17 of the 17 eyes that underwent brachytherapy. Enucleation was performed in 5 (29.42%) of these patients due to recurrence with diffuse tumor involvement, and 4 of the tumors were located anterior to the equator. In 12 (70.58%) patients, the eyes were protected from enucleation following local brachytherapy. Radioactive plaque brachytherapy can be applied as an effective salvage therapy with successful results in retinoblastoma patients who have received initial systemic or intra-arterial chemotherapy. Post equator-located solitary tumors have the highest success rate.

Current status and treatment concept of transcatheter arterial chemoembolization on the era of systemic chemotherapy for hepatocellular carcinoma

Current status and treatment concept of transcatheter arterial chemoembolization on the era of systemic chemotherapy for hepatocellular carcinoma

Managing 5FU Cardiotoxicity in Colorectal Cancer Treatment.

Fluorouracil (5FU) is the backbone chemotherapy agent in the treatment of colorectal cancer (CRC). Cardiotoxicity represents an uncommon but serious side effect of treatment with 5FU. Here, we review the current literature on 5FU-cardiotoxicity in the setting of CRC specifically, with a focus on data from the modern era of combination chemotherapy. Despite decades of study, there is little consensus on risk factors and biomarkers for 5FU-cardiotoxicity, nor how patients with CRC should be managed following a cardiotoxicity event. Given the elevated risk of recurrent cardiotoxicity on rechallenge, the use of alternative regimens that do not contain 5FU is a critical aspect of management. Data on the cardiotoxicity risk and efficacy of non-5FU regimens in CRC are therefore reviewed in detail.