Systemic Chemotherapy In Patients Research Articles

Impact of perioperative chemotherapy on survival outcome of advanced colorectal cancer patients treated with cytoreduction and hyperthermic intraperitoneal chemotherapy: A retrospective study.

e15570 Background: Colorectal cancer (CRC) with peritoneal carcinomatosis (PC) is generally associated with poor prognosis. The present study aims to assess potential value of perioperative systemic chemotherapy in patients treated with cytoreductive surgery with HIPEC (CRS/HIPEC) in a single institute in Saudi Arabia. Methods: We included CRC with PC who underwent CRS/ HIPEC from January 2012 till December 2019. Different clinicopathological, treatment-related factors and dates of relapse/death, were retrospectively assessed. We checked the distribution of these factors in addition to survival outcome in those who received perioperative chemotherapy vs. none. Results: We recruited 127 eligible patients (79 patients [62.2%] received systemic chemotherapy). Patients with no perioperative chemotherapy were more likely to have grade 1 tumours (62.5% vs. 25.3%, p < 0.0001), mucinous adenocarcinoma (41.7% vs. 12.7%, p = 0.002), normal CEA ≤5 ng/dl (70.2% vs. 47.4%, p = 0.016) and peritoneal-only metastasis (66.7% vs. 45.6%, p = 0.021). Median PFS and OS were 34 and 62.2 months, respectively. Patients with no perioperative systemic chemotherapy had significantly better PFS and OS (median PFS: not reached vs. 19 months, HR = 0.29, 95% CI = 0.15-0.59, p < 0.0001, OS :HR = 4.3, 95% CI 1.3-14.3, p = 0.009). After adjustment of different prognostic factors, there was no significance difference in OS between the two groups (HR = 3.8, 95% CI = 0.98-14.71, p = 0.053), while PFS was still significantly better in the no chemotherapy group (HR = 2.52, 95% CI = 1.13-5.63, p = 0.024). Conclusions: CRS/HIPEC provided favourable survival outcome in our study cohort especially in patients with more favourable prognostic features. No survival benefit with perioperative chemotherapy could be demonstrated.

Gene Expression Profiling in Early Breast Cancer-Patient Stratification Based on Molecular and Tumor Microenvironment Features.

Patients with early-stage hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) are typically treated with surgery, followed by adjuvant systemic endocrine therapy with or without adjuvant chemotherapy and radiation therapy. Current guidelines regarding the use of adjuvant systemic therapy depend on clinical and pathological factors, such as the morphological assessment of tumor subtype; histological grade; tumor size; lymphovascular invasion; and lymph node status combined with estrogen receptor, progesterone receptor, and HER2 biomarker profiles assessed using immunohistochemistry and in situ hybridization. Additionally, the prognostic and predictive value of tumor-infiltrating lymphocytes and their composition is emerging as a key marker in triple negative (TNBC) and HER2-enriched molecular breast tumor subtypes. However, all these factors do not necessarily reflect the molecular heterogeneity and complexity of breast cancer. In the last two decades, gene expression signatures or profiling (GEP) tests have been developed to predict the risk of disease recurrence and estimate the potential benefit of receiving adjuvant systemic chemotherapy in patients with luminal breast cancer. GEPs have been utilized to help physicians to refine decision-making process, complementing clinicopathological parameters, and can now be used to classify the risk of recurrence and tailoring personalized treatments. Several clinical trials using GEPs validate the increasing value of such assays in different clinical settings, addressing relevant clinical endpoints. Finally, the recent approval of immune checkpoint inhibitors in TNBC and the increasing use of immunotherapy in different molecular BC populations highlight the opportunity to refine current GEPs by including a variety of immune-related genes that may help to improve predicting drug response and finetune prognosis.

Short-course radiotherapy and chemotherapy for conversion surgery in patients with unresectable metastatic rectal cancer: a preliminary case series study.

Curative treatment is challenging in patients with locally advanced rectal cancer and unresectable metastases. The aim of this study was to evaluate the clinical outcomes of short-course radiotherapy (RT) followed by systemic chemotherapy for patients with rectal cancer with mesorectal fascia (MRF) involvement and unresectable distant metastases. The study included consecutive patients diagnosed as having metastatic mid-to-low rectal cancer treated with short-course RT followed by systemic chemotherapy for conversion radical or palliative surgery between 2014 and 2019 at Gil Medical Center. The patients had primary rectal tumors involving the MRF and unresectable distant metastases. The treatment strategies were determined in a multidisciplinary team discussion. Seven patients (five men and two women) underwent short-course RT (5×5 Gy) and preoperative systemic chemotherapy. The median age was 68 years (range, 46-84 years), and the median distance from the anal verge to the primary tumor was 6.0 cm (range, 2.0-9.0 cm). During the median follow-up period of 29.4 months, three patients underwent conversion radical surgery with R0 resection, two underwent palliative surgery, and two could not undergo surgery. No postoperative major morbidity or mortality occurred. The patients who underwent conversion complete radical surgery showed good long-term survival outcomes, with an overall survival time of 29.4-48.8 months and progression-free survival time of 14.7-41.1 months. Short-course RT followed by systemic chemotherapy could provide patients with unresectable stage IV rectal cancer a chance to undergo to conversion radical surgery with good long-term survival outcomes.

Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy

BackgroundUnresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy.Patients and methodsIn this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator’s choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks.ResultsFifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively.ConclusionsEndoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.

Stereotactic Body Radiation Therapy for the First-Line Comprehensive Treatment of Oligometastatic Nasopharyngeal Carcinoma: A Prospective, Single-Arm, Phase II Trial

The current treatment strategy for patients with metastatic nasopharyngeal carcinoma (NPC) is mainly based on palliative chemotherapy, with low complete remission rate and poor progression-free survival (PFS). Radiation therapy has proven efficacy in the treatment of patients with nonmetastatic NPC, with emerging indication in the setting of limited metastatic disease. We proposed a single-arm phase II study to determine if metastasis-directed SBRT plus systemic treatment could prolong PFS compared with historical findings at first-line therapy for patients with oligometastatic NPC.We enrolled metastatic NPC with 1-5 metastatic lesions, with all metastases amenable to SBRT. Prescribed doses ranged from 25-50 Gy administered in five fractions. All patients received systemic chemotherapy before or after SBRT. The primary endpoint was PFS at 1 year from the start of SBRT treatment.Between October 2016 and January 2020, 24 patients with a median age of 48 years (range, 29-65 years) were recruited. A total of 44 sites were treated with 11 of 24 patients receiving SBRT to more than one site. Spinal bone was most often irradiated. By Kaplan-Meier actuarial analysis, 1-year PFS was 62% and overall survival rate 87%. Most patients progressed in new distant sites with only one local SBRT failures out of 44 lesions. Patients with lung metastasis had a lower chance of distant progression than those with bone metastasis or liver metastasis. There were no SBRT relevant grade 3-5 toxicity, and only one patient suffered from grade 2 adverse event.Use of metastasis-directed SBRT with systemic chemotherapy for patients with oligometastatic NPC as first-line therapy was well tolerated, and resulted in high PFS, substantially greater than historical values for patients who only received systemic agents.

Impact of Primary Tumor Resection on Mortality in Patients with Stage IV Colorectal Cancer with Unresectable Metastases: A Multicenter Retrospective Cohort Study

Primary tumor resection (PTR) before commencing systemic chemotherapy in patients with stage IV colorectal cancer and unresectable metastases (mCRC) remains controversial. This study aimed to assess whether PTR before systemic chemotherapy is associated with mortality in mCRC patients, after adjusting for confounding factors, such as the severity of the primary tumor and metastatic lesions. We analyzed hospital-based cancer registries from nine designated cancer hospitals in Fukushima Prefecture, Japan. Patients were divided into two groups (PTR and non-PTR), based on whether PTR was performed as initial therapy for mCRC or not. The primary outcome was all-cause mortality. Kaplan-Meier survival analysis was performed, and survival estimates were compared using the log-rank test. Adjusted hazard ratios were calculated using Cox regression to adjust for confounding factors. All tests were two-sided; P-values < 0.05 were considered statistically significant. Between 2008 and 2015, 616 mCRC patients were included (PTR: 414 [67.2%]; non-PTR: 202 [32.8%]). The median follow-up time was 18.0 (interquartile range [IQR]: 8.4-29.7) months, and 492 patients (79.9%) died during the study period. Median overall survival in the PTR and non-PTR groups was 23.9 (IQR: 12.2-39.9) and 12.3 (IQR: 6.2-23.8) months, respectively (P < 0.001, log-rank test). PTR was significantly associated with improved overall survival (adjusted hazard ratio: 0.51; 95% confidence interval: 0.42-0.64, P < 0.001). PTR before systemic chemotherapy in patients with mCRC was associated with improved survival.

P-117 Survival outcomes following systemic chemotherapy in stage IVA/B high-grade mucinous appendiceal cancer after unsuccessful cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

The appropriate management of patients with unresectable mucinous appendiceal cancer (MAC) with peritoneal spread (Stage IVA/B) after a failed attempt at cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is unclear. Systemic chemotherapy (SCT) may be an option; however, data regarding its effectiveness in stage IVA/B MAC is controversial. This study aimed to assess outcomes after SCT in patients with unresectable peritoneal metastases from high-grade MAC. A single-center retrospective cohort study was conducted using a prospective CRS/HIPEC database. Stage IVA/B high-grade MAC patients deemed surgical candidates, but had an aborted CRS/HIPEC or underwent only palliative HIPEC were included. Overall survival (OS) was compared between patients with postoperative SCT and those without. Among 80 identified patients, 20 received SCT and 60 did not (NoCT). There was no difference between groups in age (p=0.314), sex (p=0.796), proportion of newly diagnosed patients (p=0.893), histopathologic subtype (p=0.108), preoperative chemotherapy (p=0.962), preoperative tumor markers (CA 19-9, CA 125, CEA), and postoperative major complication rates (p=0.358). Both groups had extensive residual disease (median peritoneal cancer index: 39 vs 39, p=0.956). SCT regimens included: 5-FU/capecitabine in 25% (n=5), FOLFOX in 30% (n=6), FOLFIRI in 30% (n=6), FOLFIRINOX in 5% (n=1) with/without bevacizumab. Regimens were unknown in 10% (n=2). Median number of cycles was 12 (IQR: 6-15) and median time between the procedure and SCT was 7 (IQR: 5-10) weeks. Median follow-up was 65 months. Median OS was significantly higher in the SCT group (26 months; 95%CI: 10.8-41.5) versus NoCT group (10 months; 95%CI: 7.3-12.7) (p < 0.0001), with hazard ratio 0.30 (95%CI: 0.16-0.57, p < 0.0001). Systemic chemotherapy improves overall survival in high-grade MAC patients with unresectable peritoneal metastases who were deemed surgical candidates, but underwent an unsuccessful CRS/HIPEC attempt. Further prospective studies with a larger sample size are required to identify patient subgroups who benefit the most from SCT.

Systemic chemotherapy in patients with brain only metastatic breast cancer: A retrospective analysis.

1093 Background: The treatment of patients with brain only metastatic breast cancer (BO-MBC) remains very challenging. There is also very limited literature informing on appropriate treatment or natural history of this entity. Systemic chemotherapy in addition to targeted therapy and/or anti-estrogen treatment is often used, but little is known if it adds to the overall or disease free survival. In this retrospective study, we examine this, as well as other factors which may be associated with increased risk of CNS or systemic recurrence in these patients. Methods: A database search at a single institution identified 178 patients with brain metastases (BM) from breast cancer out of which 45 patients had BO-MBC between 2007-2020. We collected demographic, clinical, radiographic and other treatment data. Leptomeningeal disease (LMD) was diagnosed by cerebrospinal fluid (CSF) cytology, neuroimaging, or both. We used the Brookmeyer and Crowley method. Results: The patients were followed for a median of 17.9 months; 36 out of 45 patients (80%) received local treatment for BM (surgery/radiation/both) and HER2 directed antibodies or tyrosine kinase inhibitors and/or anti-estrogen treatment, whereas 9 out of 45 patients (20%) received systemic chemotherapy in addition. There were 22 out of 45 (49%) HER2 +, 5 out of 45 (11%) HR + and 18 out of 45 (40%) triple negative breast cancer (TNBC) patients. There were 17 out of 45 patients (38%) who were deemed to have low burden of BM (defined as one to three BM and largest being ≤3 cm) whereas there were 24 out of 45 patients (53%) who had high burden of BM (defined as four or more BM or largest being &gt; 3 cm). Conclusions: Patients with BO-MBC represent a distinct entity. Despite having better survival than patients with BM and extra CNS disease these patients have a high risk of developing LMD, CNS and systemic recurrences. The addition of chemotherapy to targeted therapy and/or anti-estrogens does not decrease the rates of systemic or CNS recurrence. The ER+ subset have a lower rate of development of systemic disease, as expected due to their relatively indolent biology. The CNS and systemic recurrence seem to be higher in patients with HER2+ cancers and counterintuitively even in those with low burden of BM; albeit these were statistically insignificant.[Table: see text]

Hepatic Artery Infusion of Floxuridine in Combination With Systemic Chemotherapy for Pancreatic Cancer Liver Metastasis: A Propensity Score-Matched Analysis in Two Centers.

AimTo evaluate the efficacy of hepatic artery infusion (HAI) of floxuridine (FUDR) in combination with systemic chemotherapy in patients with pancreatic cancer liver metastases (PCLM).Patients and MethodsWe retrospectively collected clinical data of 347 patients with PCLM who underwent first-line chemotherapy at two Chinese centers between 2012 and 2019. Propensity score matching between patients with and without HAI was performed to compensate for differences in baseline characteristics. Objective response rate (ORR) and overall survival (OS) between groups were compared. HAI pump functionality was recorded.ResultsData of 258 patients (62 patients with HAI and 196 patients without HAI) were used for matching. After 1:1 ratio matching, 62 patients per group were included. The intrahepatic ORR was 66.1% in the HAI group and 22.6% in the non-HAI group (P < 0.001), and the extrahepatic ORR was 25.0 versus 28.9% (P = 0.679). The median OS was significantly longer in HAI group (14.0 versus 10.8 months, P = 0.001). Multivariance COX regression showed HAI led to a decrease in hazard ratio for death by 61.8% (HR = 0.382; 95% CI: 0.252–0.578; P< 0.001). Subgroup analysis revealed that patients without EHM, with higher intrahepatic tumor burden and with synchronous liver metastasis benefited more from HAI. Dysfunction of HAI pump occurred in 5.7% of patients during the period of follow-up.ConclusionsIn patients with PCLM, first-line treatment with HAI FUDR plus SCT resulted in higher intrahepatic response and better OS.

A STUDY OF DRUG UTILIZATION IN PATIENTS OF CARCINOMA BREAST RECEIVING SYSTEMIC CHEMOTHERAPY IN TERTIARY CARE HOSPITALS

Objective: The objective of the study is to study drug utilization in patients with breast carcinoma receiving systemic chemotherapy in government as well as private set-up.&#x0D; Methods: This was a record-based, retrospective-prospective study, analyzing the prescription pattern of drugs used for systemic chemotherapy in patients diagnosed with carcinoma breast at government teaching hospital (GTH) and private trust hospital (PTH) for 1 year in 600 patients. Patient’s demographic, clinical, and therapeutic data were collected from the files and personal interviews and analyzed in Microsoft Excel.&#x0D; Results: Diagnosis of breast carcinoma was highest in age bracket of 40–49 years (32.33% GTH and 32.67% PTH), and the most common presenting symptom was painless lump (76.33% GTH and 83% PTH). In GTH, most frequently prescribed regimen was 4AC → 4T → RT (17.33%). In PTH, most commonly prescribed regimen was 6FEC → RT (19.33%). Highest prescribed drugs were A (32.8%), C (29.12%), and F (20.24%) in GTH and A (32.26%), F (31.68%), and E (16.45%) in PTH. Average number of drugs prescribed per prescription was 12.55 and 11.37; percentage of chemotherapeutic agents prescribed by generic name was 100 and 95.02, and from the WHO essential drug list (2015) was 96.43 and 82.77 in GTH and PTH, respectively (A= Cyclophosphamide, C= Doxorubicin, T=Taxanes [Paclitaxel/Docetaxel], F=5-fluorouracil, E=Epirubicin, RT=Radiotherapy, → followed by, the number indicates chemotherapy cycle).&#x0D; Conclusion: The study results can help in generating local data regarding drug use pattern of the systemic chemotherapeutic agents in breast cancer patients and promote rational drug use.

Clinical outcomes of systemic therapy in patients with unresectable or metastatic combined hepatocellular-cholangiocarcinoma.

The optimal systemic chemotherapy for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not yet been defined. The definition and classification of cHCC-CCA has changed recently in the 5th edition of WHO classification. We reviewed the pathological findings with the new classification and analysed the efficacy of systemic chemotherapy in patients with unresectable/metastatic cHCC-CCA. Among 254 patients with histologically confirmed cHCC-CCA from 1999 to 2015 in Asan Medical Center, Seoul, Korea, 99 patients who received systemic chemotherapy for unresectable/metastatic disease were included. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were retrospectively evaluated. Sorafenib (n=62) and cytotoxic chemotherapy (n=37) were administered as first-line chemotherapies; the ORR was 14.1%, and the median PFS and OS were 3.8 and 10.6months, respectively, with a median follow-up duration of 39.6months. The efficacy outcomes were not significantly different between patients who received sorafenib and those who received cytotoxic chemotherapy (ORR, 9.7% vs 21.6%, P=.14; median PFS, 4.2 vs 2.9months, P=.52; median OS, 10.7 vs 10.6months, P=.34). In multivariate analysis, large intrahepatic tumour burden (≥30% of liver volume), elevated serum bilirubin and non-platinum containing first-line chemotherapy remained as significant prognostic factors for poorer OS. The efficacy outcomes according to first-line treatment were not significantly different between sorafenib and cytotoxic chemotherapy, and pathological findings were not found to help for determining appropriate therapeutic agent or assessing the prognosis. To overcome the poor treatment outcomes, further studies are needed to find proper treatment targets, biomarkers and the best treatment strategies.

Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review.

Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.

Hepatic Artery Infusion Pump Combined With Systemic Chemotherapy for Patients With Liver Metastases From Breast Carcinoma.

Background: When liver metastasis in patients with breast cancer is diagnosed, treatment is generally palliative and usually consists of systemic therapies only. This study aimed to evaluate the efficacy and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy in patients with breast carcinoma liver metastases (BCLM). Methods: From January 2012 to December 2019, HAI catheter systems were implanted under the guide of digital subtract angiography (DSA) in 19 patients with BCLM. All patients received systemic chemotherapy and HAI gemcitabine plus floxuridine (FUDR). Methods: The overall response rate (ORR) of intrahepatic lesions was 73.7%, including 2 patients (10.5%) with complete remission (CR) and 12 patients (63.2%) with partial remission (PR). Additionally, we found that young patients (age < 55 years) had a higher ORR than the older (100% vs 44.4%, P = .011). The median overall survival (mOS) was 13.1 months. Kaplan-Meier survival curves demonstrated that the mOS was not significantly different between patients with < 9 intrahepatic lesions and those with ≥ 9 lesions (13.7 months vs 10.9 months, P = .225). The mOS was 14.3 and 10.6 months for patients without extrahepatic metastases and with extrahepatic metastases, respectively (P = .016). None of the patients had grade 4 toxicity. The grade 3 toxicities included leucopenia, neutropenia and diarrhea. Conclusions: HAI gemcitabine plus FUDR combined with systemic chemotherapy is effective in achieving a high local response and prolonging mOS for patients with BCLM and is associated with a relatively low rate of toxicity.

Population-Based Study on Practice Variation Regarding Preoperative Systemic Chemotherapy in Patients with Colorectal Liver Metastases and Impact on Short-Term Outcomes

Introduction: Indications for preoperative chemotherapy for colorectal liver metastases (CRLM) vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study assesed variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. Methods: All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national auditing database. Case-mix factors contributing to use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. Results: In total, 4323 (69.6%) patients were included of whom 1314 (31.1%) patients received preoperative chemotherapy and 3009 patients did not. Patients receiving chemotherapy were younger (mean (+SD) 63.3 (10.2) versus 67.1 (10.3) p< 0.01) and had less comorbidity (Charlson scores 2+ (18% versus 27%, p< 0.01). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 4% and 100%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.22, 0.97 - 1.53, p = 0.09), 30-day morbidity (OR 1.16, 0.90 - 1.48, p = 0.25) or 30-day mortality (OR 1.18, 0.68 - 2.01, p = 0.55) was observed. Conclusions: Significant hospital variation in use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and preoperative chemotherapy was observed.

Apparent Diffusion Coefficient Can Predict Response to Chemotherapy of Liver Metastases in Colorectal Cancer

The aim of this meta-analysis was to evaluate the suitability of apparent diffusion coefficient (ADC) as a predictor of response to systemic chemotherapy in patients with metastatic colorectal carcinoma (CRC). MEDLINE library, SCOPUS database, and EMBASE database were screened for relationships between pretreatment ADC values of hepatic CRC metastases and response to systemic chemotherapy. Overall, five eligible studies were identified. The following data were extracted: authors, year of publication, study design, number of patients, mean value ADC and standard-deviation, measure method, b-values, and Tesla-strength. The methodological quality of every study was checked according to the Quality Assessment of Diagnostic Studies-2 instrument. The meta-analysis was undertaken by employing RevMan 5.3 software. DerSimonian and Laird random-effects models with inverse-variance weights were used to account for heterogeneity. Mean ADC values including 95% confidence intervals were calculated. Five studies (n = 114 patients) were included. The pretreatment mean ADC in the responder group was 1.15 × 10-3 mm2/s (1.03, 1.28) and 1.37 × 10-3 mm2/s (1.3, 1.44) in the nonresponder group. An ADC baseline threshold of 1.2 × 10-3 mm2/s, below which no nonresponder was found, can distinguish both groups. The results indicate ADC can serve as a predictor of response to chemotherapy for CRC patients.

Impact of noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy on bladder-sparing strategy in patients with muscle-invasive bladder cancer

ObjectiveTo identify the optimal selection criteria for bladder sparing strategy with transurethral resection of bladder tumor (TURBT) and systemic chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MethodsWe conducted a retrospective cohort study in 71 patients with MIBC (T2-4aN0M0) who desire to bladder preservation received neoadjuvant chemotherapy (NAC) after maximal TURBT, followed by clinical restaging and second-TURBT. Fifty-eight of 71 patients with no residual tumor on the second-TURBT were placed on conservative management for bladder sparing (BS). Noninvasive down-staging (NID) was defined as cT0/Ta/Tis/T1N0 at first-TURBT after NAC and no residual tumor on second-TURBT. Overall survival (OS) and cystectomy-free survival (CFS) were assessed according to the response of NAC in the BS group by using Kaplan-Meier methods. Cox proportional hazards regression model was used to identify independent variables predicting OS. ResultsAt a median follow-up of 40 months 5-year OS and CFS in patients with NID and non-NID were 89.1% versus 20.8% and 84.8% versus 16.7%, respectively.Multivariate analysis showed that the ≥3 cycles of NAC (hazard ratio [HR] 0.14, 95% confidential index [CI] 0.03–0.7; P = 0.017) and achievement of NID (HR 0.11, 95% CI 0.03–0.46, P = 0.002) favorably associated with OS. ConclusionsPatients who achieved NID might be optimal candidates for the bladder sparing strategy with maximum TURBT plus NAC followed by second-TURBT.

Systemic chemotherapy promotes HIF-1α-mediated glycolysis and IL-17F pathways in cutaneous T-cell lymphoma.

Systemic chemotherapy is often the last resort of advanced cutaneous T-cell lymphoma (CTCL). Tumor recurrence and adverse effects of systemic chemotherapy are the main limitations. We aim to investigate the metabolic alterations in tumor cells after CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy. In advanced CTCL, CHOP chemotherapy has no survival benefit and the duration of response is significantly inferior to other canonical treatments. HIF-1α is significantly elevated in lesions of advanced MF patients as well as tumor cell line Hut78 and tumor xenograft mice model. CHOP therapy also increased glycolytic activities in a HIF-1α-dependent manner. In CTCL xenograft tumor mice model, lesional cells showed a significant increase in IL-17F after chemotherapy, shifting toward a Th17 phenotype, which process is also regulated by HIF-1α. Echinomycin, HIF-1α inhibitor, was co-administered in xenograft tumor mouse models with CHOP and showed a significant reduction in tumor growth. CHOP chemotherapy promotes glycolysis and IL-17 pathways in a HIF-1α-dependent fashion. Furthermore, HIF-1α blockade is promising as an accompanying agent in systemic chemotherapy for patients with advanced CTCL.

Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the effectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreated (adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.37–0.73, p < 0.001), and not in desmoplastic patients (adjusted HR 1.78, 95% CI 0.75–4.21, p = 0.19). In pretreated patients no significant effect of adjuvant CTx was observed, neither in the desmoplastic group (adjusted HR 0.83, 95% CI 0.49–1.42, p = 0.50) nor in the non-desmoplastic group (adjusted HR 0.96, 95% CI 0.71–1.29, p = 0.79). Similar results were found for DFS, with a superior DFS in non-desmoplastic patients treated with adjuvant CTx (HR 0.71, 95% CI 0.55–0.93, p < 0.001) that were not pretreated. Adjuvant CTx seems to improve OS and DFS after resection of non-desmoplastic CRLM. However, this effect was only observed in patients that were not treated with chemotherapy.

Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes

IntroductionDefinitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. Materials and methodsAll patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. ResultsIn total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found. ConclusionSignificant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found.

Hepatic Arterial Infusion Combined with Systemic Chemotherapy for Patients with Extensive Liver Metastases from Gastric Cancer.

PurposeLiver metastases in patients with gastric cancer often indicate poor prognosis. Once liver metastases are extensive, it is difficult to achieve disease control by using systemic chemotherapy alone. The purpose of this study was to evaluate the effect and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy on extensive liver metastases from gastric cancer.Patients and MethodsBetween 2012 and 2019, 21 patients with extensive liver metastases from gastric cancer (LMGC) were enrolled in our study. Liver metastases were identified as unresectable and a major factor affecting prognosis mainly based on size and number of intrahepatic lesions. All patients received systemic chemotherapy with S-1 and HAI oxaliplatin plus floxuridine (FUDR).ResultsLiver metastases in 16 patients (76.2%) were evaluated as H3. The overall response rate was 76.2% (9.5% complete response). Intrahepatic and extrahepatic median progression-free survival times were 9.5 and 5.2 months, respectively. Median survival time (MST) was 12.3 months. All patients did not have the toxicity of grade 4. Grade 3 toxic effects included bone marrow suppression (14.3%) and diarrhea (9.5%). The other treatment-related toxicities were mild and reversible.ConclusionHAI combined with systemic chemotherapy for extensive LMGC seems to be safe and effective, which achieves a high-local response and may contribute to long survival time for patients.