Primary Tumor-Related Complications and Salvage Outcomes in Patients with Metastatic Rectal Cancer and an Untreated Primary Tumor.
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ABSTRACT:
SUBMITTER: Tan WJ
PROVIDER: S-EPMC7931667 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeWe investigated how features relating to pelvic cavity anatomy and tumor hemodynamic factors may influence systemic failure in rectal cancer.Materials and methodsRectal cancer patients (207 women, 343 men), who had been prospectively enrolled onto six cohorts and given curative-intent therapy, were analyzed for the first metastatic event. In one of the cohorts, the diameter of the inferior mesenteric vein (IMV) was assessed on diagnostic abdominal computed tomography images (n = 113). Tumor volume (n = 193) and histologic response to neoadjuvant therapy (n = 445) were recorded from diagnostic magnetic resonance images and surgical specimens, respectively.ResultsMore women than men developed lung metastasis (p = 0.037), while the opposite was the case for liver metastasis (p = 0.040). Wider IMV diameter correlated with larger tumor volume (r = 0.481, p < 0.001) and male sex (p < 0.001). Female sex was the only adverse prognostic factor for lung metastasis. When sex, tumor volume, and histologic response were taken into consideration, poor tumor response remained the only determinant for liver metastasis (p = 0.002).ConclusionsIn a diverse rectal cancer population given curative-intent treatment, women and men had different outcome with regard to the primary metastatic site. Tumor hemodynamic factors should be considered in rectal cancer risk stratification.
| S-EPMC6909215 | biostudies-literature
Project description:IntroductionCancer patients are at risk for severe complications related to the underlying malignancy or its treatment and, therefore, usually require admission to intensive care units (ICU). Here, we evaluated the clinical characteristics and outcomes in this subgroup of patients.Materials and methodsSecondary analysis of two prospective cohorts of cancer patients admitted to ICUs. We used multivariable logistic regression to identify variables associated with hospital mortality.ResultsOut of 2,028 patients, 456 (23%) had cancer-related complications. Compared to those without cancer-related complications, they more frequently had worse performance status (PS) (57% vs 36% with PS?2), active malignancy (95% vs 58%), need for vasopressors (45% vs 34%), mechanical ventilation (70% vs 51%) and dialysis (12% vs 8%) (P<0.001 for all analyses). ICU (47% vs. 27%) and hospital (63% vs. 38%) mortality rates were also higher in patients with cancer-related complications (P<0.001). Chemo/radiation therapy-induced toxicity (6%), venous thromboembolism (5%), respiratory failure (4%), gastrointestinal involvement (3%) and vena cava syndrome (VCS) (2%) were the most frequent cancer-related complications. In multivariable analysis, the presence of cancer-related complications per se was not associated with mortality [odds ratio (OR) = 1.25 (95% confidence interval, 0.94-1.66), P = 0.131]. However, among the individual cancer-related complications, VCS [OR = 3.79 (1.11-12.92), P = 0.033], gastrointestinal involvement [OR = 3.05 (1.57-5.91), P = <0.001] and respiratory failure [OR = 1.96(1.04-3.71), P = 0.038] were independently associated with in-hospital mortality.ConclusionsThe prognostic impact of cancer-related complications was variable. Although some complications were associated with worse outcomes, the presence of an acute cancer-related complication per se should not guide decisions to admit a patient to ICU.
| S-EPMC5072702 | biostudies-literature
Project description:The emerging debate between primary tumor location and clinical outcome of bevacizumab treated metastatic colorectal cancer (mCRC) continues. The aim of the present study is to investigate the association between the primary tumor location and clinical outcome of 115 mCRC patients receiving bevacizumab based treatment. A meta-analysis including 21 studies was carried out to confirm the conclusion. In our prospective study, we found that right-sided mCRC commonly occurred in older cases (p = 0.03) with multiple-site metastasis (p = 0.03). Progression-free survival (PFS) of the left-sided patients undergoing bevacizumab plus a FOLFIRI regimen was superior to the right-sided cases (p = 0.03, crude HR = 0.31, 95%CI = 0.11–0.87; adjusted HR = 0.21, 95%CI = 0.06–0.66). The meta-analysis confirmed that efficacy of bevacizumab-based treatment in left-sided mCRC patients was better than the right-sided cases in the overall population (Ph = 0.24, combined OR = 1.36, 95%CI = 1.07–1.72), RAS/BRAF wild-type (Ph = 0.19, combined OR = 1.66, 95%CI = 1.17–2.34), clinical trial (Ph = 0.23, combined OR = 1.42, 95%CI = 1.07–1.88), Caucasian population (Ph = 0.18, combined OR = 1.37, 95%CI = 1.02–1.85) and first-line (Ph = 0.19, combined OR = 1.48, 95%CI = 1.13–1.96) subgroups. Improved survival of bevacizumab plus chemotherapy treated left-sided mCRC patients was observed in the overall population [Ph < 0.01, combined MSR = 1.09, 95%CI = 1.00–1.18 for PFS; Ph < 0.01, combined MSR = 1.24, 95%CI = 1.13–1.36 for overall survival (OS)], especially in the RAS/BRAF wild-type (Ph = 0.09, combined MSR = 1.10, 95%CI = 1.03–1.19 for PFS; Ph = 0.02, combined MSR = 1.34, 95%CI = 1.21–1.49 for OS). These findings indicate that primary tumor sidedness can predict clinical outcome of bevacizumab-treated RAS/BRAF wild-type mCRC patients and the left-sided patients may benefit more from bevacizumab plus FOLFIRI.
| S-EPMC6702298 | biostudies-other
Project description:BACKGROUND:Metastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning >?300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome. METHODS:PNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n?=?121). RESULTS:The CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression. CONCLUSIONS:Measuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis.
| S-EPMC7204307 | biostudies-literature
Project description:BACKGROUND:NETTER-1 trial demonstrated high efficacy and low toxicity of four cycles of Peptide Receptor Radionuclide Therapy (PRRT) in patients with metastasized NET. The present study evaluates the outcome of further PRRT cycles in the so called salvage setting in patients after initial response to four therapy cycles and later progression. METHODS:Thirty five patients (pat.) (25 male, 10 female, 63 ± 9 years) with progressive, metastasized NET (23 small intestinal, 5 lung, 4 CUP, 1 rectal, 1 gastric and 1 paraganglioma) were included. All patients previously received 4 PRRT cycles with 177Lu-DOTATATE and showed initial response. SPECT based dosimetry was applied to determine kidney and tumor doses. Therapy response was evaluated using 68Ga-DOTATATE PET/CT (with high dose CT), CT alone or MRI (RECIST 1.1), toxicity was defined using CTCAE 5.0 criteria. 99mTc99-MAG3 scintigraphy was used to assess potential renal tubular damage. Progression free survival (PFS) and Overall survival (OS) analysis was performed with the Kaplan-Meier-method. RESULTS:The median PFS after initial PRRT was 33 months (95% CI: 30-36). The mean cumulative dose for including salvage PRRT was 44 GBq (range 33.5-47). One pat. (2.9%) showed grade 3 hematotoxicity. Kidney dosimetry revealed a mean cumulative kidney dose after a median of 6 PRRT cycles of 23.8 Gy. No grade 3 / 4 nephrotoxicity or relevant decrease in renal function was observed. Follow-up imaging was available in 32 patients after salvage therapy. Best response according to RECIST 1.1. was PR in one patient (3.1%), SD in 26 patients (81.3%) and PD in 5 patients (15.6%). PFS after salvage therapy was 6 months (95% CI: 0-16; 8 patients censored). Mean OS after initial PRRT was 105 months (95% CI: 92-119) and 51 months (95% CI: 41-61) after start of salvage therapy. Median OS was not reached within a follow-up of 71 months after initial PRRT and 25 months after start of salvage PRRT, respectively. CONCLUSIONS:Salvage therapy with 177Lu-DOTATATE is safe and effective even in patients with extensive previous multimodal therapies during disease progression and represents a feasible and valuable therapy option for progressive NET.
| S-EPMC6686531 | biostudies-other
Project description:The recent development of multiple targeted agents for metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm; hence the benefit and optimal timing of cytoreductive nephrectomy is being reevaluated.To determine primary tumor response to treatment with targeted agents in patients with mRCC.We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between November 2004 and December 2009 without prior systemic treatment who received targeted therapy with their primary tumor in situ.Two independent reviewers measured the diameter of primary and metastatic tumors at baseline and subsequent scans, using Response Evaluation Criteria Solid Tumors (RECIST) v.1.1 to assess disease response.We identified 168 consecutive patients with a median 15 mo of follow-up and a median maximum tumor diameter of 9.6 cm. Median maximum primary tumor response was -7.1% (interquartile range: -14.0 to -0.1). A total of 61 patients had multiple studies available for evaluation. In 43 patients with <10% decrease in primary tumor within in the first 60 d, median maximum response was -7.2% at 154 d versus -24.5% maximum response at 174.5 d for 18 patients with ?10% decrease in primary tumor during the initial 60 d.Decrease in primary tumor diameter >30% while on targeted therapy for mRCC is rare, with most patients demonstrating minimal or no decrease in primary tumor diameter. Early response predicts a better overall primary tumor response.
| S-EPMC4378833 | biostudies-other
Project description:We aimed to identify risk factors that predict functional imaging (FI) response to salvage chemotherapy and evaluate outcomes following autologous stem cell transplant (ASCT) in primary refractory Hodgkin Lymphoma (HL). From 1 October 1994 to 10 July 2015, 192 primary refractory HL patients were treated on sequential second line protocols. Event-free survival (EFS) and overall survival (OS) were calculated from the date of histological confirmation of refractory disease. Covariates were analysed for relationship with FI response and EFS. By intent-to-treat, the median EFS was 8·9 years and OS 10·4 years with 41% having positive post-salvage FI. On multivariate analysis, the presence of B symptoms and bulk ≥5 cm predicted for positive FI, with odds ratios of 2·15 and 2·03, respectively. For the 167 (87%) transplanted patients, 60% had a negative pre-ASCT FI. Median EFS and OS were not reached with at a median follow-up of 3·6 years in surviving patients. Both stage IV refractory disease and persistent FI abnormality pre- ASCT were associated with worse outcomes: 3-year EFS was 84%, 54% and 28% for zero, 1 and 2 risk factors, respectively (P < 0·001). Further studies are needed to validate our prognostic model and to determine optimal therapy for patients with multiple risk factors.
| S-EPMC5554509 | biostudies-other
Project description:ObjectiveTo evaluate the efficacy and safety of single-agent sunitinib as salvage treatment in Chinese patients with multidrug-resistant metastatic breast cancer (MBC).Results37 patients were enrolled with median age of 48 years. 17 had hormone receptor (HR)-positive tumors, 7 had HER2-positive tumors, and 10 had triple-negative tumors. Among 32 evaluable patients with follow-up, 6 (18.8%) achieved partial response, 14 (43.8%) achieved stable disease, and 11 (34.4%) exhibited tumor shrinkage. The response rate in 9 patients with carcinomatous ulcers was 77.8%. The median progression free survival (PFS) was 8.6 weeks. Patients with a better response had improved overall survival and PFS relative to patients with a worse response (p = 0.007, p < 0.001). Compared with HR-negative tumor, HR-positive tumor had significantly better response to sunitinib (p = 0.035). The most frequent non-hematologic adverse events were fatigue (82.8%) and hypertension (34.5%). Grade 3/4 hematologic toxicity included neutropenia (82.8%) and thrombocytopenia (79.3%). There was no correlation between the clinical response and IHC findings.Materials and methodsPatients with MBC who were resistant to multiple salvage regimens (? 3 previous chemotherapy lines) were enrolled to receive sunitinib monotherapy. Dosage adjustment was allowed depending on adverse events. 14 patients underwent immunohistochemistry (IHC) testing for VEGF, PDGFR, EGFR and c-KIT.ConclusionsSunitinib salvage treatment provided modest antitumor effect to patients with refractory multidrug-resistant MBC, especially to those with troublesome carcinomatous ulcers. The treatment-related adverse events of sunitinib were manageable through dosage adjustment.
| S-EPMC5295398 | biostudies-literature
Project description:BACKGROUNDThe incidence of rectal neuroendocrine tumors (NETs) is rapidly increasing because of the frequent use of endoscopic screening for colorectal cancers. However, the clinical outcomes of endoscopic resection for rectal NETs are still unclear. The aim of this study was to assess the rates of histologically complete resection (H-CR) and recurrence after endoscopic mucosal resection (EMR) for rectal NETs.METHODSA retrospective analysis was performed on patients who underwent EMR for rectal NETs between January 2002 and March 2015 at Seoul National University Hospital. Primary outcomes were H-CR and recurrence rates after endoscopic resection. H-CR was defined as the absence of tumor invasion in the lateral and deep margins of resected specimens.RESULTSAmong 277 patients, 243 (88%) were treated with conventional EMR, 23 (8%) with EMR using a dual-channel endoscope, and 11 (4%) with EMR after precutting. The median tumor size was 4.96 mm (range, 1-22) in diameter, and 264 (95%) lesions were confined to the mucosa and submucosal layer. The en-bloc resection rate was 99% and all patients achieved endoscopically complete resection. The H-CR rates were 75, 74, and 73% for conventional EMR, EMR using a dual-channel endoscope, and EMR after precutting, respectively. Multivariate analysis showed that H-CR was associated with tumor size regardless of endoscopic treatment modalities (p?=?0.023). Of the 277 patients, 183 (66%) underwent at least 1 endoscopic follow-up. Three (2%) of these 183 patients had tumor recurrence, which was diagnosed at a median of 62.5 months (range 19-98) after endoscopic resection. There was 1 case of disease-related death, which occurred 167 months after endoscopic treatment because of bone marrow failure that resulted from tumor metastasis.CONCLUSIONSAlthough the en-bloc resection rate was 99% in rectal NETs, H-CR rates were 72-74% for various EMR procedures. H-CR may be associated with tumor size regardless of endoscopic treatment modalities.
| S-EPMC5987588 | biostudies-literature
Project description:Background:Defunctioning stoma is widely used to reduce anastomotic complications in rectal cancer surgery. However, the complications of stoma and stoma reversal surgery should not be underestimated. Furthermore, in some patients, stoma reversal failed. Here, we investigated the complications of defunctioning stoma surgery and subsequent reversal surgery and identify risk factors associated with the failure of getting stoma reversed. Methods:In total, 154 patients who simultaneously underwent low anterior resection and defunctioning stoma were reviewed. Patients were divided into two groups according to whether their stoma got reversed or not. The reasons that patients received defunctioning stoma and experienced stoma-related complications and the risk factors for failing to get stoma reversed were analysed. Results:The mean follow-up time was 47.54 (range 4.0-164.0) months. During follow-up, 19.5% of the patients suffered stoma-related long-term complications. Only 79 (51.3%) patients had their stomas reversed. The morbidity of complications after reversal surgery was 45.6%, and these mainly consisted of incision-related complications. Multivariate analyses showed that pre-treatment comorbidity (HR = 3.17, 95% CI 1.27-7.96, P = 0.014), postoperative TNM stage (HR = 2.55, 95% CI 1.05-6.18, P = 0.038), neoadjuvant therapy (HR = 2.75, 95% CI 1.07-7.05, P = 0.036), anastomosis-related complications (HR = 4.52, 95% CI 1.81-11.29, P = 0.001), and disease recurrence (HR = 24.83, 95% CI 2.90-213.06, P = 0.003) were significant independent risk factors for a defunctioning stoma to be permanent. Conclusions:Defunctioning stoma is an effective method to reduce symptomatic anastomotic leakage, but the stoma itself and its reversal procedure are associated with high morbidity of complications, and many defunctioning stomas eventually become permanent. Therefore, surgeons should carefully assess preoperatively and perform defunctioning stomas in very high risk patients. In addition, doctors should perform stoma reversal surgery more actively to prevent temporary stomas from becoming permanent.
| S-EPMC7451586 | biostudies-literature