Adjuvant chemotherapy and outcome in patients (pts) with nodal (N-) and resection margin negative (R0) pancreatic adenocarcinoma (PC): A systematic review and meta-analysis.

4114 Background: Adjuvant chemotherapy following PC resection improves overall survival (OS). It is uncertain whether benefit is influenced by nodal and resection status or other factors. Methods: A systematic review of electronic databases identified published phase 2/3 studies investigating use of adjuvant chemotherapy in pts with resected PC. Efficacy (disease-free survival [DFS], OS, 5 yr OS) was explored using meta-analysis. Subgroup analysis explored effects based on nodal/resection status. Meta-regression also explored influence of age, gender, performance status [PS] and proportion of pts with head of pancreas (HOP) tumors on benefit of adjuvant chemotherapy. Results: Ten studies comprising 3644 pts were included. Two prospective phase 2 studies; 8 phase 3 trials. Median age was 63 yrs (range 24-84), 46% male. In 2268 pts with PS reported; 42% were PS 0, 51% PS 1. Tumor location was reported in 719 pts; 82% had HOP tumors. Of 3524 pts with available data; 33% N- and 67% R0. Overall, in studies of experimental vs control, adjuvant therapy significantly improved DFS (HR 0.67, CI 0.48-0.93, P = 0.02), OS (HR 0.77, 95% CI 0.68-0.87, P < 0.001) and odds of death risk at 5 yrs (OR 0.53, 95% CI 0.41-0.70, P < 0.001). In studies comparing chemotherapy to surgery only, adjuvant therapy also significantly improved DFS (HR 0.57, 95% CI 0.49-0.76, P < 0.001) and OS (HR 0.74, 95% CI 0.64-0.87, P < 0.001). There was a numerical but non-significant greater effect of adjuvant therapy in N- vs N+ pts (HR 0.58 vs 0.71, P for difference = 0.29). There was no difference in effect between pts with R0 or R1 disease (HR 0.70 vs 0.69, P for difference = 0.95). There was greater OS benefit from adjuvant therapy in pts with PS 0 (P = 0.04) and significantly less benefit on 5 yr OS in pts with HOP tumors (P = 0.04). Conclusions: The relative benefit of adjuvant chemotherapy seems similar in N-/N+ and in R0/R1 pts. This will translate into greater absolute benefit in the N+ and R1 pts due to their greater absolute risk of recurrence/death. Adjuvant chemotherapy is recommended for all pts with resected PC, where clinically appropriate, and greater benefit was seen in pts with PS 0 and body/tail tumors.

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Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200307000-00001 ◽

2003 ◽

Vol 13 (4) ◽

pp. 395-404 ◽

Cited By ~ 7

Author(s):

B. Winter-Roach ◽

L. Hooper ◽

H. Kitchener

Keyword(s):

Systematic Review ◽

Ovarian Cancer ◽

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Early Stage ◽

Meta Analysis ◽

Disease Free Survival ◽

Significant Difference ◽

Well Differentiated ◽

Platinum Chemotherapy

A systematic review and meta analysis has been undertaken in order to evaluate the effectiveness of adjuvant therapy following surgery for early ovarian cancer. Trials reported since 1990 have been of a higher quality enabling a meta analysis of adjuvant chemotherapy vs adjuvant radiotherapy and a meta analysis of adjuvant chemotherapy vs observation. There was no significant difference between radiotherapy and chemotherapy, though these comprised studies which demonstrated considerable heterogeneity. Chemotherapy did confer significant benefit over observation in terms of both overall and disease free survival. Except for women in whom adequate surgical staging has revealed well differentiated disease confined to one or both ovaries with intact capsule, platinum chemotherapy should be offered to reduce risk of recurrence.

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The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.364 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 364-364 ◽

Cited By ~ 4

Author(s):

J. J. Biagi ◽

M. Raphael ◽

W. D. King ◽

W. Kong ◽

W. J. Mackillop ◽

...

Keyword(s):

Systematic Review ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Publication Bias ◽

Meta Analysis ◽

Disease Free Survival ◽

Significant Heterogeneity ◽

Risk Of Death ◽

The Impact ◽

The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

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Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

Journal of Clinical Oncology ◽

10.1200/jco.2004.03.087 ◽

2004 ◽

Vol 22 (16) ◽

pp. 3395-3407 ◽

Cited By ~ 218

Author(s):

Alvaro Figueredo ◽

Manya L. Charette ◽

Jean Maroun ◽

Melissa C. Brouwers ◽

Lisa Zuraw

Keyword(s):

Systematic Review ◽

Colon Cancer ◽

Overall Survival ◽

Adjuvant Therapy ◽

Meta Analysis ◽

Disease Free Survival ◽

Stage Ii ◽

Free Survival ◽

Stage Ii Colon Cancer ◽

Disease Free

Purpose To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy? Methods A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation. Results Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07). Conclusion There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

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Does chemotherapy improve survival in muscle-invasive bladder cancer (MIBC)? A systematic review and meta-analysis (MA) of randomized controlled trials (RCT).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4544 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4544-4544 ◽

Cited By ~ 4

Author(s):

Angelina Tjokrowidjaja ◽

Chee Lee ◽

Martin R. Stockler

Keyword(s):

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Fixed Effects ◽

Large Scale ◽

Meta Analysis ◽

Randomised Trial ◽

Local Treatment ◽

Disease Free Survival ◽

P Value ◽

P Values

4544 Background: There is strong evidence that neoadjuvant chemotherapy improves survival in MIBC but its uptake in clinical practice is variable. The benefits of adjuvant chemotherapy are controversial, especially with the recent presentation of 3 RCTs not included in previous MA.We sought to summarise the effects of chemotherapy, both neoadjuvant and adjuvant, on survival in MIBC. Methods: We included published summary data from recent MA and RCTs. Eligible RCTs compared the addition of chemotherapy, neoadjuvant or adjuvant, to local treatment versus local treatment alone. We searched CENTRAL, PubMed, MEDLINE, proceedings of ASCO and clinicaltrials.gov from 2004 to August 2012.The primary outcome was overall survival (OS). Disease-free survival (DFS) and adverse events (AE) were secondary outcomes. Pooled hazard ratios (HR), confidence intervals (CI) and p-values (p) were estimated with fixed effects model. Heterogeneity and subgroup effects were assessed with p-values for interaction. Results: We included 21 RCTs (n=3986), 12 of neoadjuvant (n=3047) and 9 adjuvant chemotherapy (n=939).The addition of chemotherapy significantly improved OS (HR 0.86, 95% CI 0.79 to 0.93, p=0.0004). Separate analyses of neoadjuvant therapy and adjuvant therapy yielded significant results in both subgroups (HR 0.89, 95% CI 0.81 to 0.98, p=0.02; HR 0.75, 95% CI 0.63 to 0.90, p=0.002; respectively; p-value for interaction 0.11). There were larger benefits in DFS (HR 0.77, 95% CI 0.71 to 0.84, p<0.000001), which were also noted with the addition of neoadjuvant and adjuvant therapy (HR 0.80 95% CI 0.73 to 0.88, p<0.00001; HR 0.67 95% CI 0.55 to 0.81, p<0.0001; respectively; p-value for interaction 0.10). The most common AE of grade 3 or 4 were haematological, gastrointestinal and renal impairment with median frequencies of 33%, 15% and 2% respectively in neoadjuvant; and 15%, 21% and 27% in adjuvant trials. Conclusions: Meta-analysis of available randomized trials indicates that chemotherapy, both adjuvant and neoadjuvant, improves survival in MIBC. A direct comparison of these two strategies in a large scale randomised trial is needed to determine which is optimal.

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Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline

Journal of Clinical Oncology ◽

10.1200/jco.2016.67.5553 ◽

2016 ◽

Vol 34 (21) ◽

pp. 2541-2556 ◽

Cited By ~ 169

Author(s):

Alok A. Khorana ◽

Pamela B. Mangu ◽

Jordan Berlin ◽

Anitra Engebretson ◽

Theodore S. Hong ◽

...

Keyword(s):

Systematic Review ◽

Pancreatic Cancer ◽

Palliative Care ◽

Adjuvant Chemotherapy ◽

Primary Tumor ◽

Performance Status ◽

Disease Free Survival ◽

Preoperative Therapy ◽

Psychological Status ◽

Free Survival

Purpose To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer. Methods ASCO convened a panel of medical oncology, radiation oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. Results Nine randomized controlled trials met the systematic review criteria. Recommendations A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki .

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Exercise efficacy and prescription during treatment for pancreatic ductal adenocarcinoma: a systematic review

BMC Cancer ◽

10.1186/s12885-020-07733-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dominic O’Connor ◽

Malcolm Brown ◽

Martin Eatock ◽

Richard C. Turkington ◽

Gillian Prue

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Physical Function ◽

Meta Analysis ◽

Ductal Adenocarcinoma ◽

Key Stakeholders ◽

The Impact

Abstract Background Surgical resection remains the only curative treatment for pancreatic cancer and is associated with significant post-operative morbidity and mortality. Patients eligible for surgery, increasingly receive neo-adjuvant therapy before surgery or adjuvant therapy afterward, inherently exposing them to toxicity. As such, optimizing physical function through exercise during treatment remains imperative to optimize quality of life either before surgery or during rehabilitation. However, current exercise efficacy and prescription in pancreatic cancer is unknown. Therefore, this study aims to summarise the published literature on exercise studies conducted in patients with pancreatic cancer undergoing treatment with a focus on determining the current prescription and progression patterns being used in this population. Methods A systematic review of four databases identified studies evaluating the effects of exercise on aerobic fitness, muscle strength, physical function, body composition, fatigue and quality of life in participants with pancreatic cancer undergoing treatment, published up to 24 July 2020. Two reviewers independently reviewed and appraised the methodological quality of each study. Results Twelve studies with a total of 300 participants were included. Heterogeneity of the literature prevented meta-analysis. Exercise was associated with improvements in outcomes; however, study quality was variable with the majority of studies receiving a weak rating. Conclusions High quality evidence regarding the efficacy and prescription of exercise in pancreatic cancer is lacking. Well-designed trials, which have received feedback and input from key stakeholders prior to implementation, are required to examine the impact of exercise in pancreatic cancer on key cancer related health outcomes.

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Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-140287 ◽

2021 ◽

pp. postgradmedj-2021-140287

Author(s):

Ahmad Fariz Malvi Zamzam Zein ◽

Catur Setiya Sulistiyana ◽

Wilson Matthew Raffaello ◽

Arief Wibowo ◽

Raymond Pranata

Keyword(s):

Systematic Review ◽

Absolute Risk ◽

Controlled Trial ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Intervention Group ◽

Control Group ◽

Reduce Mortality Rate ◽

Icu Admission ◽

Clinical Recovery

PurposeThis systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19.MethodsWe performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs).ResultsThere were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000.ConclusionSOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery.Protocol registrationPROSPERO: CRD42021247510.

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Rise and fall of total mesorectal excision with lateral pelvic lymphadenectomy for rectal cancer: an updated systematic review and meta-analysis of 11,366 patients

International Journal of Colorectal Disease ◽

10.1007/s00384-021-03946-2 ◽

2021 ◽

Author(s):

Gabriele Anania ◽

Richard Justin Davies ◽

Alberto Arezzo ◽

Francesco Bagolini ◽

Vito D’Andrea ◽

...

Keyword(s):

Systematic Review ◽

Rectal Cancer ◽

Total Mesorectal Excision ◽

Neoadjuvant Therapy ◽

Functional Outcomes ◽

Meta Analysis ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Mesorectal Excision ◽

Timeline Analysis

Abstract The role of lateral lymph node dissection (LLND) during total mesorectal excision (TME) for rectal cancer is still controversial. Many reviews were published on prophylactic LLND in rectal cancer surgery, some biased by heterogeneity of overall associated treatments. The aim of this systematic review and meta-analysis is to perform a timeline analysis of different treatments associated to prophylactic LLND vs no-LLND during TME for rectal cancer. Methods A literature search was performed in PubMed, SCOPUS and WOS for publications up to 1 September 2020. We considered RCTs and CCTs comparing oncologic and functional outcomes of TME with or without LLND in patients with rectal cancer. Results Thirty-four included articles and 29 studies enrolled 11,606 patients. No difference in 5-year local recurrence (in every subgroup analysis including preoperative neoadjuvant chemoradiotherapy), 5-year distant and overall recurrence, 5-year overall survival and 5-year disease-free survival was found between LLND group and non LLND group. The analysis of post-operative functional outcomes reported hindered quality of life (urinary, evacuatory and sexual dysfunction) in LLND patients when compared to non LLND. Conclusion Our publication does not demonstrate that TME with LLND has any oncological advantage when compared to TME alone, showing that with the advent of neoadjuvant therapy, the advantage of LLND is lost. In this review, the most important bias is the heterogeneous characteristics of patients, cancer staging, different neoadjuvant therapy, different radiotherapy techniques and fractionation used in different studies. Higher rate of functional post-operative complications does not support routinely use of LLND.

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