Neoadjuvant talimogene laherparepvec plus surgery vs surgery alone for resectable stage IIIB-IVM1a melanoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182162 | GEO | 2021/09/01
REPOSITORIES: GEO
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Project description:Neoadjuvant talimogene laherparepvec plus surgery vs surgery alone for resectable stage IIIB-IVM1a melanoma
| PRJNA755196 | ENA
Project description:ObjectiveThe optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. Surgery is the primary treatment but with poor results. Attempts to improve patient survival have been made by introducing chemotherapy, radiotherapy, or both. However, randomized comparisons for all these strategies are not always available. This network meta-analysis compared the overall survival of neoadjuvant and adjuvant therapy with surgery alone to identify the most effective approach.MethodsWe systematically searched electronic databases (PubMed, Embase, and Cochrane Library) for relevant studies published before April 2021. Only phase II and III randomized controlled trials comparing the following treatments were included: surgery alone, neoadjuvant chemotherapy (NCT), radiotherapy (NRT) or chemoradiotherapy (NCRT), adjuvant chemotherapy (ACT), radiotherapy (ART), or chemoradiotherapy (ACRT). The hazard ratios (HR) and 95% confidence intervals (CIs) of overall survival (OS) was identified as the measurement of effectiveness. A network meta-analysis was conducted to synthesize the evidence under the Bayesian framework, and the relative effects of all possible comparisons were made. The ranking analysis was performed to support the decision in clinical practice.ResultsA total of 19 relevant trials with 3,749 patients were identified. Compared with surgery alone, NCRT (HR 0.76, 95% CI 0.65-0.89) and NCT (HR 0.81, 95% CI 0.70-0.94) significantly improved OS, while other treatments, including NRT (HR 0.86, 95% CI 0.66-1.08), ACRT (HR 0.73, 95% CI 0.49-1.08), ACT (HR 0.96, 95% CI 0.75-1.21), and ART (HR 0.86, 95% CI 0.66-1.14), provided no significant survival advantage. None of the neoadjuvant and adjuvant treatments showed a statistically significant difference in OS to each other when compared in pairs.ConclusionFor resectable esophageal squamous cell carcinoma, this network meta-analysis showed that NCRT may be the optimal strategy, NCT may be the second choice, while other multimodality treatments could not improve OS compared with surgery alone. It remains unclear whether ESCC will benefit from adding radiotherapy into the neoadjuvant treatment.Systematic review registrationWe registered this meta-analysis protocol at the prospective register of systematic reviews, PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=172745 (Identification code: CRD42020172745).
| S-EPMC8564474 | biostudies-literature
Project description:BACKGROUND:Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. METHODS:MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. RESULTS:In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8?months for neoadjuvant treatment and 14·8?months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0?months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P?<?0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P?<?0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P?=?0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P?<?0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. CONCLUSION:Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.
| S-EPMC6033157 | biostudies-literature
Project description:Median OS after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially "curative" R0 resection. To achieve better local control, neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist.The underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% compared to patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous, standardized technique of histopathologically handling Whipple specimens will be applied at all participating centers. Overall, 410 patients (n=205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial.For the first time, the NEOPA study investigates the impact of neoadjuvant CRT on survival of resectable pancreas head cancer in a prospectively randomized manner. The results of the study have the potential to change substantially the treatment regimen of pancreas cancer.Clinical Trial gov: NCT01900327, DRKS00003893, ISRCTN82191749.
| S-EPMC4057592 | biostudies-literature
Project description:BackgroundThe impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node-negative esophageal cancer.MethodsWe searched the Surveillance, Epidemiology, and End Results database for patients with clinically node-negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer-specific survival.ResultsA total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node-negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P < 0.01). After matching, nCRT was associated with improved five-year overall survival for pT3-4N0 (localized) disease (59.6% vs. 37.7%; P < 0.001) and pathological node-positive disease (60.5% vs. 40.7%; P = 0.002). Cox multivariate regression analysis revealed that the addition of nCRT for truly node-negative patients with tumor length ≥ 3 cm, pT1-2N0 (early-staged) and localized disease were independent risk factors for survival than surgery alone (P < 0.01).ConclusionsCompared with surgery alone, patients with cN0 esophageal cancer with pathological node-positive or localized true node-negative disease gain a significant survival benefit from nCRT. However, nCRT plus surgery was associated with decreased survival for early-staged true node-negative patients. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.
| S-EPMC7471040 | biostudies-literature
Project description:Surgery is the standard of care for patients with operable non-small cell lung cancer (NSCLC). However, as a single modality, surgery for early stage or locally advanced NSCLC remains associated with high rates of local and distant recurrence. The addition of neoadjuvant or adjuvant chemotherapy has modestly improved outcomes. While systemic therapy paired with surgery for other malignancies such as breast cancer have resulted in far better outcomes for equivalent stage designations, outcome improvements for operable NSCLC have lagged in part as a result of trials where adjuvant chemotherapy seemed to incur harm for stage IA patients and only modest survival benefit for stage IB-IIIA patients (AJCC 7th ed.). In recent years, immunotherapy for NSCLC has emerged as a systemic therapy with significant benefit over traditional chemotherapy regimens. These advances with immune checkpoint inhibitors (ICIs) have opened the door to administering peri-operative immunotherapy for operable NSCLC. As a result, a great multitude of studies investigating the use of immunotherapy in combination with surgery for NSCLC as well as several other malignancies have emerged. In this review, we outline the rationale for neoadjuvant immunotherapy in the treatment of operable NSCLC and summarize the available evidence that include preoperative ICI as a single modality or in combination with systemic agents and/or radiotherapy. Further, we summarize how such treatment trajectories open multiple unique windows of opportunity for scientific discovery and potential therapeutic gains for these vulnerable patients.
| S-EPMC7867741 | biostudies-literature
Project description:We performed bulk RNA sequencing of tumor biopsies from patients before treatment, on-treatment and in case a poor response was suspected from the resection specimen. At baseline we found in responding patients a higher six-gene IFNy score compared to non-responders. On-treatment non-responders showed either high expression of co-inhibitory checkpoints with a high number of cytotoxic lymphocytes or low expression and a low number of cytotoxic lymphocytes.
2021-02-04 | GSE165252 | GEO
Project description:BACKGROUND:Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. METHODS:An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and two-way deterministic and probabilistic Monte Carlo sensitivity analysis. RESULTS:SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04% or below 75.68% in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway. CONCLUSION:Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient's likelihood of receiving multimodal treatment in either pathway.
| S-EPMC6394923 | biostudies-literature
Project description:Docetaxel, cisplatin, and 5-fluorouracil (DCF) significantly improved overall survival in metastatic gastroesophageal adenocarcinoma (GEA). The aim of this study was to assess efficacy of DCF regimen as perioperative chemotherapy compared with surgery alone in patients with resectable GEA. We identified 789 patients who underwent surgery alone and 62 patients who received at least one cycle of DCF regimen consisting of docetaxel (75 mg/m2 on day 1), cisplatin (75 mg/m2 on day 1), and 5-fluorouracil (750 mg/m2 /day on continuous perfusion on days 1 to 5), every 3 weeks. Overall survival was compared using Cox proportional hazards regression model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched-pair analysis. In Cox multivariate analysis weighted by IPTW, DCF group was associated with favorable overall survival (OS) compared with the surgery group (HR = 0.59; 95% CI, 0.45-0.78; P = 0.0003). For the matched-pair analysis (comparing 41 patients for each group with the same baseline characteristics), median OS was 22 months and 57 months for the surgery group and DCF group, respectively (log-rank P = 0.0011). In Cox multivariate analysis, DCF group was associated with favorable OS compared with the surgery group (HR = 0.29; 95% IC, 0.14-0.64; P = 0.0019). In the matched-pair population, major complications (Dindo-Clavien grade 3-5) arose in six patients (14.63%) in the DCF group and seven patients (17.07%) in the surgery group (P = 1). Perioperative DCF chemotherapy is superior to surgery alone in terms of OS. A randomized phase III trial should compare DCF to standard perioperative regimens.
| S-EPMC5119963 | biostudies-literature
Project description:Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress.
| S-EPMC4734931 | biostudies-literature