Predictors of treatment attrition in patients with metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18041-e18041 ◽  
Author(s):  
Arvin Bahrabadi ◽  
Jenny Ruan ◽  
Gillian Gresham ◽  
Winson Y. Cheung
Keyword(s):  
Cancer Progression ◽  
Positive Impact ◽  
Multivariable Analysis ◽  
Treatment Algorithm ◽  
Attrition Rate ◽  
Line Treatment ◽  
Treatment Attrition ◽  
Clinical Factors ◽  
First Line ◽  
First Line Treatment

e18041 Background: Although the treatment landscape of cancer has evolved significantly with the introduction of novel and more efficacious drugs, the positive impact of these new therapies may be limited by attrition and ultimately non-exposure to later lines of therapy. Using a population-based cohort of mCRC, our aims were to characterize rates of attrition and determine factors associated with failure to receive each line of treatment. Methods: Medical records of patients who were diagnosed with mCRC from 2008-10 and referred to any 1 of 5 cancer centers in British Columbia were merged with systemic therapy data from the provincial pharmacy database. We classified patients into mutually exclusive treatment categories: a) receipt of all available lines of mCRC therapies; b) attrition directly attributable to disease, such as cancer progression or death; c) attrition attributable to other clinical factors, including toxicity, and d) attrition secondary to non-clinical factors, including personal/social circumstances. Multivariate logistic regression models were constructed to identify predictors. Results: We identified 525 eligible mCRC patients: median age 64 years, 57% men, 55% Caucasian, 68% ECOG 0/1, 41% and 35% never and ever smokers, respectively. The attrition rate was 40% (95% confidence interval [95% CI], 36%-44%) for first line treatment, 25% (95% CI, 19%-31%) for second line treatment and 14% (95% CI, 5.5%-22.5%) for third line. While cancer progression (31%) and chemo toxicity (30%) were the most common causes of attrition, other frequent reasons included death (20%) and patient preference (14%). On multivariable analysis, first-line treatment attrition was associated with worse baseline ECOG (odds ratio [OR], 1.92; p < 0.001) and older age at diagnosis of mCRC (OR, 1.04; p < 0.001). When we examined attrition over all lines, it was significantly correlated with worse ECOG (OR, 2.44; p < 0.001). Conclusions: Treatment attrition is a prevalent problem in mCRC and can hinder the benefits that would otherwise be possible with a sequential treatment algorithm. Some causes of attrition are potentially modifiable and may reflect opportunities for patients to maximize exposure to all lines of therapies.

First-line treatment algorithm and guidelines in center-involving diabetic macular edema

2019 ◽  
Vol 29 (6) ◽  
pp. 573-584 ◽  
Author(s):  
Laurent Kodjikian ◽  
David Bellocq ◽  
Francesco Bandello ◽  
Anat Loewenstein ◽  
Usha Chakravarthy ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Treatment Algorithm ◽  
Individual Characteristics ◽  
Diabetic Patients ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Literature Evidence ◽  
First Line Treatment

Management of center-involving diabetic macular edema represents a real therapeutic challenge. Diabetic macular edema is the leading cause of visual acuity impairment in diabetic patients. Since the advent of intravitreal drugs, management of diabetic macular edema has significantly evolved. The historical grid laser photocoagulation is no longer recommended as first-line treatment of diabetic macular edema owing to the findings of the pivotal randomized controlled trials, and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids also represent a valid treatment option in the management of naïve diabetic macular edema and their efficacy has also been confirmed in several studies. The optimal treatment for diabetic macular edema should consider both general and ophthalmological comorbidities. Patient compliance and motivation should also be carefully evaluated as some treatments require monthly follow-up. Based on recent literature evidence, the present review provides clinicians with a first-line treatment algorithm for center-involving diabetic macular edema tailored to the patient’s individual characteristics.

scholarly journals Cambridge Protocol for Management of Segmental Bone Loss

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Tennyson ◽  
Ada Maria Krzak ◽  
Matija Krkovic ◽  
Ali Abdulkarim
Keyword(s):  
Bone Loss ◽  
Treatment Algorithm ◽  
Bone Defects ◽  
Definitive Treatment ◽  
Soft Tissue Coverage ◽  
Line Treatment ◽  
First Line ◽  
Fine Wire ◽  
Segmental Bone ◽  
First Line Treatment

Abstract Introduction: Segmental long bone defects are some of the most challenging to surgically reconstruct; however, there is no clear guidance on which of the myriad of techniques is superior in a given clinical context. We describe three cases of segmental bone loss presenting to a major trauma center and have use these to develop a treatment algorithm for the sub-acute management of such fractures. Case Report: Case 1 – Acute shortening and delayed lengthening using lengthening intramedullary (IM) nail to treat diaphyseal non-union of the femur with associated 3 cm shortening. Case 2 – 15 cm traumatic bone loss of femur, failed Masquelet, treated with IM nail, monolateral external-fixation and cable with a mean lengthening rate of 46 days/cm. Case 3 – 12 cm tibial traumatic bone loss, failed Masquelet, treated with fine wire frame with a mean lengthening rate of 49 days/cm. Conclusion: As our cases illustrate; attempting complicated, definitive management in the acute phase generates complications and necessitates re-intervention. As such, we have developed a treatment algorithm for traumatic segmental bone loss. We recommend waiting 6 weeks and reimaging to check for evidence of spontaneous bone formation before deciding on definitive treatment. First-line treatment for femoral defects <4 cm is acute limb shortening with delayed lengthening using lengthening IM nail. First-line treatment for femoral defects >4 cm is lengthening over nail with monolateral external fixator. First-line treatment of tibial segmental bone defects in our hands is fine wire circular frames which provide excellent scope for soft tissue coverage and deformity correction. Treatment times of over 2 years in a frame are not uncommon and patients must diligently comply with pin sites management and lengthening protocols. This is the first paper providing an algorithm to guide surgeons in choosing the best lower limb reconstruction options in the sub-acute setting; considering the skill s

Neutrophil to lymphocyte ratio and response to tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 477-477 ◽  
Author(s):  
Arnoud J. Templeton ◽  
Eitan Amir ◽  
Priya Aneja ◽  
Francisco Emilio Vera-Badillo ◽  
Thomas Hermanns ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Line Treatment ◽  
First Line ◽  
Lymphocyte Ratio ◽  
Tki Treatment ◽  
First Line Treatment

477 Background: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are markers of host inflammation and have prognostic value in many solid tumors. Here we aimed to explore the association of NLR and PLR with response to tyrosine kinase inhibitor (TKI) treatment in metastatic renal cell carcinoma (mRCC). Methods: Data from patients with mRCC treated at the Princess Margaret Cancer Centrein Toronto with a TKI as first-line treatment were retrospectively collected. The association of several variables with response to treatment (complete response [CR] or partial response [PR] vs. stable disease > 3 months [SD] or progressive disease [PD]) was assessed by binary logistic regression. Significant variables were dichotomized and cut-offs selected by the area under the receiver operating characteristic (AUC) curve. Results: Data from 157 patients treated between 11/2004 and 09/2012 were analyzed. Median age at start of TKI treatment was 61 years and first-line treatment was sunitinib, sorafenib, and other in 49%, 43%, and 8% of patients, respectively. Best response was CR/PR, SD, and PD in 27%, 55%, and 18% patients. On multivariable analysis NLR > 2.5 and Karnofsky Performance Status (KPS) < 90% were associated with a lower likelihood of response and each allocated a score of 1 unit. Response rates for a score of 0, 1, or 2 were 45% (29-61%), 28% (17-38%), 10% (1-19%), respectively. PLR did not retain association with response in multivariable analysis. Conclusions: NLR and KPS are associated with response to TKI treatment in mRCC. Data from an external validation set will also be presented.

Genetic polymorphisms of CCL5 and CCR5 to predict efficacy of cetuximab-based treatment in metastatic colorectal cancer patients depending on primary tumor location.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3594-3594 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Shu Cao ◽  
Sebastian Stintzing ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Genetic Polymorphisms ◽  
Multivariable Analysis ◽  
Tumor Location ◽  
Line Treatment ◽  
Control Cohort ◽  
First Line ◽  
First Line Treatment

3594 Background: EGFR signaling blockade increases CCL5 expression, which attracts with tumor-infiltrating leukocytes regulating either the host-derived anti-tumor immunity or tumor progression. We tested whether genetic polymorphisms in the CCL5/CCR5 axis could predict efficacy of cetuximab (CET)-based first-line treatment in metastatic colorectal cancer (mCRC) patients (pts). Methods: Genomic DNA was extracted from 491 samples of two different cohorts with KRAS wild-type mCRC in the FIRE-3 study: an evaluation cohort of 244 pts receiving CET plus FOLFIRI (median age 64 yrs; median follow-up 34.1 mos); and a control cohort of 247 pts receiving bevacizumab plus FOLFIRI (median age 65 yrs; median follow-up 39.4 mos); Single nucleotide polymorphisms (SNPs) of CCL5 and CCR5 genes were analyzed by PCR-based direct sequencing. Results: Pts in the evaluation cohort with any CCL5 rs2280789 G allele had shorter OS compared to those with the A/A variant (19.9 vs. 33.4 mos, HR 1.56, 95%CI: 1.05–2.30, P= 0.024), which was confirmed in multivariable analysis (HR 1.64, P= 0.015). Pts carrying any CCR5 rs1799988 T allele had a trend lower response rate than those with the C/C variant (68 vs. 81%, P= 0.078). Statistically significant differences in efficacy were shown between the groups consisting SNPs and tumor location (Table). The findings were not confirmed in the control cohort. Conclusions: Genetic variants of CCL5 and CCR5 SNPs may predict outcomes in mCRC pts receiving CET-based first-line treatment depending on tumor location. [Table: see text]

scholarly journals Canadian consensus: A new systemic treatment algorithm for advanced EGFR-mutated NSCLC

2020 ◽  
Vol 27 (2) ◽  
Author(s):  
B. Melosky ◽  
S. Banerji ◽  
N. Blais ◽  
Q. Chu ◽  
R. Juergens ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Checkpoint Inhibitors ◽  
Treatment Algorithm ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Central Nervous System Activity ◽  
Clinical Questions ◽  
Egfr Mutated ◽  
First Line Treatment

Background Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised: ■ What is the optimal first-line treatment for patients with EGFR-mutated nsclc? ■ What is preferred first-line treatment for patients with brain metastasis? ■ What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)? ■ What is the preferred treatment after osimertinib? ■ What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? Methods A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. Results The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. Conclusions This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.

scholarly journals Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA)

2018 ◽  
Vol 25 (1) ◽  
pp. 90 ◽  
Author(s):  
M. Uccello ◽  
M. Moschetta ◽  
G. Mak ◽  
T. Alam ◽  
C. Murias Henriquez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Optimal Algorithm ◽  
Treatment Algorithm ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
New Paradigm ◽  
First Line ◽  
First Line Treatment

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabinebased therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm.

scholarly journals Haematopoietic Score for the Prognostic Evaluation of Multiple Myeloma Patients Undergoing First-line Treatment With a Bortezomib-based Regimen

2020 ◽  
Author(s):  
JingSong He ◽  
XiaoYan Yue ◽  
XiaoYan Han ◽  
DongHua He ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Multivariable Analysis ◽  
New Drugs ◽  
Line Treatment ◽  
First Line ◽  
Prognostic Predictors ◽  
Cell Percentage ◽  
Treatment Centre ◽  
First Line Treatment

Abstract Backgroud: It is very important to evaluate the prognosis of multiple myeloma (MM) patients before starting treatment. Although haematopoietic status may have a significant impact on patient survival, it has not received sufficient attention in current clinical practice.Methods:This was a retrospective study of 150 newly diagnosed MM patients treated in one hematonosis treatment centre from May 2013 to June 2016, all of whom received first-line treatment with a bortezomib-based regimen.The effects of haematopoietic factors, including haemoglobin levels (Hgb <100 g/L), mean corpuscular volume (MCV>99.1 fL), and platelet count (<150 × 10E9/L), on the prognosis of the patients were analysed. Each of the above factors was assigned a value of 1 to generate a haematopoietic score.Results: According to the results, 59 (39.3%) patients had a score of 0, 43 (28.7%) had a score of 1, 29 (19.3%) had a score of 2, and 19 (12.7%) had a score of 3. The median PFS times were 43.1, 24.5, 32.6 and 14.2 months, respectively (P<0.001), and the median OS times were NR, 47.1 months, NR and 31.4 months, respectively (P<0.001). Multivariable analysis showed that the R-ISS stage (3 vs 1-2, HR, 1.4), haematopoietic score (3 vs 0-2, HR, 1.91) and plasma cell percentage (>30%, HR, 1.96) are independent prognostic predictors for PFS; age (≤65 years, HR, 0.54), the Durie-Salmon stage (3B vs 1-3a, HR, 2.96), haematopoietic score (3 vs 0-2, HR, 2.53) and the bone marrow plasma cell percentage (>30%, HR, 2.35) are independent prognostic predictors of OS. Conclusion: This study suggests that the haematopoietic score can be used to evaluate the prognosis of newly treated MM patients in the era of new drugs. However, there is still a need to enlarge the number of cases and carry out prospective research to validate this conclusion.

scholarly journals Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer

2021 ◽  
Author(s):  
Miguel Gonzalez Velez ◽  
Heidi E. Kosiorek ◽  
Jan B. Egan ◽  
Andrea L. McNatty ◽  
Irbaz B. Riaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Prognostic Impact ◽  
Line Treatment ◽  
First Line ◽  
Hormone Sensitive ◽  
First Line Treatment

Abstract Background Altered tumor suppressor genes (TSG-alt) in prostate cancer are associated with worse outcomes. The prognostic value of TSG-alt in metastatic, hormone-sensitive prostate cancer (M1-HSPC) is unknown. We evaluated the effects of TSG-alt on outcomes in M1-HSPC and their prognostic impact by first-line treatment. Methods We retrospectively identified patients with M1-HSPC at our institution treated with first-line androgen deprivation therapy plus docetaxel (ADT + D) or abiraterone acetate (ADT + A). TSG-alt was defined as any alteration in one or more TSG. The main outcomes were Kaplan–Meier-estimated progression-free survival (PFS) and overall survival, analyzed with the log-rank test. Clinical characteristics were compared with the χ2 test and Kruskal–Wallis rank sum test. Cox regression was used for univariate and multivariable analyses. Results We identified 97 patients with M1-HSPC: 48 (49%) with ADT + A and 49 (51%) with ADT + D. Of 96 patients with data available, 33 (34%) had 1 TSG-alt, 16 (17%) had 2 TSG-alt, and 2 (2%) had 3 TSG-alt. The most common alterations were in TP53 (36%) and PTEN (31%); 6% had RB1 alterations. Median PFS was 13.1 (95% CI, 10.3–26.0) months for patients with normal TSGs (TSG-normal) vs. 7.8 (95% CI, 5.8–10.5) months for TSG-alt (P = 0.005). Median PFS was lower for patients with TSG-alt vs TSG-normal for those with ADT + A (TSG-alt: 8.0 [95% CI, 5.8–13.8] months vs. TSG-normal: 23.2 [95% CI, 13.1–not estimated] months), but not with ADT + D (TSG-alt: 7.8 [95% CI, 5.7–12.9] months vs. TSG-normal: 9.5 [95% CI, 4.8–24.7] months). On multivariable analysis, only TSG-alt predicted worse PFS (hazard ratio, 2.37; 95% CI, 1.42–3.96; P < 0.001). Conclusions The presence of TSG-alt outperforms clinical criteria for predicting early progression during first-line treatment of M1-HSPC. ADT + A was less effective in patients with than without TSG-alt. Confirmation of these findings may establish the need for inclusion of molecular stratification in treatment algorithms.

scholarly journals How I treat metastatic triple-negative breast cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 2) ◽  
pp. e000504 ◽  
Author(s):  
Rafael Caparica ◽  
Matteo Lambertini ◽  
Evandro de Azambuja
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Treatment Algorithm ◽  
Predictive Biomarkers ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for metastatic TNBC for a long time, this scenario has changed recently with the advent of the polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours. The present manuscript proposes a treatment algorithm for patients with metastatic TNBC based on the currently available, most relevant literature on the topic. For patients with a BRCAmut and able to tolerate chemotherapy, we recommend initiating treatment with platins (carboplatin/cisplatin) and to start PARPis at disease progression. For patients with PD-L1-positive tumours (PD-L1 expression on tumour-infiltrating immune cells ≥1%), we recommend first-line treatment with nab-paclitaxel and atezolizumab, when available. In patients without a BRCA mutation and with PD-L1-negative tumours, we recommend single-agent chemotherapy with taxanes (paclitaxel or docetaxel) as a first-line treatment. In patients with a high disease burden or who are very symptomatic, combinations such as anthracyclines plus cyclophosphamide or platins with taxanes are valid options. Chemotherapy should be maintained until the occurrence of disease progression or limiting toxicities. After progression to first-line chemotherapy, anthracyclines are an option for patients who received taxanes and vice versa. For patients who progressed to taxanes and anthracyclines, or who present contraindications to these agents, fluorouracil/capecitabine, eribulin, gemcitabine, cisplatin/carboplatin, vinorelbine and ixabepilone are alternatives. The treatment of TNBC is constantly evolving, and the inclusion of patients in ongoing trials evaluating new targeted agents, immunotherapy and predictive biomarkers should be encouraged, in an attempt to improve metastatic TNBC treatment outcomes.

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