Management of multiple myeloma

There has been no improvement in the treatment of multiple myeloma (MM) during the last decades and two meta-analyses of randomized trials recorded no significant survival benefit for combination chemotherapy compared to the classic melphalan-prednisone combination. However the past 15 years has seen several innovative strategies which have dramatically modified the management of MM. In younger patients, high-dose therapy with autologous stem cell transplantation is considered to be superior to conventional chemotherapy and is used as part of front-line therapy. A number of issues have been addressed in recent trials in order to improve the results of autologous transplantation (source of stem cells, conditioning regimen, impact of double transplants, maintenance therapy). Bisphosphonates reduce the incidence of skeletal-related events and improve the quality of life. Recombinant erythropoietin reduces red blood cell transfusion need and improves the quality of life. Thalidomide has been introduced more recently. Phase II studies with thalidomide alone or combined with dexamethasone have shown impressive response rates and this drug is currently being evaluated as part of front-line therapy. Finally, analysis of prognostic factors such as beta 2 microglobulin and cytogenetics define subgroups of patients with a completely different outcome and help the process of selecting therapeutics strategies.     

Treatment of upper tract urothelial carcinoma: a review of surgical and adjuvant therapy

Upper tract urothelial carcinoma is a disease entity that has not been as extensively studied and reviewed as carcinoma of the bladder. Recent advances in technology and adjuvant therapy have changed the treatment armamentarium of oncologists and urologists. A literature review was conducted that focused on newer surgical techniques, including laparoscopy and endoscopic management of upper tract disease. Adjuvant therapy including immunotherapy, chemotherapy, and radiation is also reviewed. Nephroureterectomy with removal of a bladder cuff still remains the gold standard of treatment. However, laparoscopic nephroureterectomy is quickly becoming popular, with equivalent recurrence rates. Because of the relatively recent introduction of laparoscopy into the urologic field, long-term data with respect to recurrence rates and survival rates are not yet available. Immunotherapy has also shown promise, but with higher recurrence rates than surgery. Chemotherapy and radiation also show some improvement in recurrence rates, but there have been no randomized, prospective trials. Endoscopic management is acceptable in patients with severe medical comorbidities or solitary kidneys but requires rigorous and close follow-up. Adjuvant therapy with either chemotherapy or radiation is still debated but does offer some improvement in disease-specific survival. Randomized, prospective, placebo-controlled studies are required but are difficult to perform because of the relatively low incidence and prevalence of this disease.     

Neoadjuvant versus adjuvant treatment: which one is better for resectable esophageal squamous cell carcinoma?

ABSTRACT: Esophageal cancer is the eighth most common cancer worldwide, and especially in some areas of China is the fourth most common cause of death and is of squamous cell carcinoma (SCC) histology in >90% of cases. Surgery alone was the mainstay of therapeutic intervention in the past, but high rates of local and systemic failure have prompted investigation into multidisciplinary management. In this review, we discuss the key issues raised by the recent availability of esophageal SCC treatment with the addition of chemotherapy, radiotherapy, and chemoradiotherapy to the surgical management of resectable disease and discuss how clinical trials and meta-analysis inform current clinical practice. None of the randomized trials that compared neoadjuvant radiotherapy or chemotherapy with surgery alone in esophageal SCC has demonstrated an increase in overall survival in those patients treated with neoadjuvant radiotherapy or chemotherapy. Neoadjuvant chemoradiotherapy has been accepted recently for esophageal cancer because such a regimen offers great opportunity for margin negative resection, improved loco-regional control and increased survival. The majority of the available evidence currently reveals that only selected locally advanced esophageal SCC are more likely to benefit from the adjuvant therapy. The focus of future trials should be on identification of the optimum regimen and should aim to minimize treatment toxicities and effect on quality of life, as well as attempt to identify and select those patients most likely to benefit from specific treatment options.     

A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases

ABSTRACT: Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT) is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS) has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.     

可切除的食管胃结合部腺癌的联合治疗

近年来胃癌的发病率有所下降,相比之下胃食管结合部腺癌的发病率却快速增长。手术治疗仍然是早期食管胃结合部腺癌的标准治疗方法,同时手术联合化疗、放化疗治疗食管胃结合部腺癌也逐渐得到国际认可。尽管在手术治疗、放疗和化疗治疗技术得到完善和改进,但食管癌和食管胃结合部腺癌的预后仍然较差。目前有数个大型临床随机对照试验数据支持对食管下端和食管胃交界部腺癌使用术前联合化疗,但辅助治疗的贡献仍不能确定。最近有meta分析表明手术联合化疗、放化疗可以提高胃食管结合部腺癌患者术后存活率,但也有一些临床随机试验的数据表明手术联合化疗、放化疗并无明显好处。本文通过总结最新的临床试验及meta分析结果,阐述不同的可切除的胃食管结合部腺癌的联合治疗方法。     

Combination of active specific immunotherapy or adoptive antibody or lymphocyte immunotherapy with chemotherapy in the treatment of cancer

Successful treatment of cancer patients with a combination of monoclonal antibodies (mAb) and chemotherapeutic drugs has spawned various other forms of additional combination therapies, including vaccines or adoptive lymphocyte transfer combined with chemotherapeutics. These therapies were effective against established tumors in animal models and showed promising results in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. Although combination between immunotherapy and chemotherapy has long been viewed as incompatible as chemotherapy, especially in high doses meant to increase anti-tumor efficacy, has induced immunosuppression, various mechanisms may explain the reported synergistic effects of the two types of therapies. Thus direct effects of chemotherapy on tumor or host environment, such as induction of tumor cell death, elimination of regulatory T cells, and/or enhancement of tumor cell sensitivity to lysis by CTL may account for enhancement of immunotherapy by chemotherapy. Furthermore, induction of lymphopenia by chemotherapy has increased the efficacy of adoptive lymphocyte transfer in cancer patients. On the other hand, immunotherapy may directly modulate the tumor’s sensitivity to chemotherapy. Thus, anti-tumor mAb can increase the sensitivity of tumor cells to chemotherapeutic drugs and patients treated first with immunotherapy followed by chemotherapy showed higher clinical response rates than patients that had received chemotherapy alone. In conclusion, combination of active specific immunotherapy or adoptive mAb or lymphocyte immunotherapy with chemotherapy has great potential for the treatment of cancer patients which needs to be confirmed in larger controlled and randomized Phase III trials.     

Results of randomized trials of immunotherapy for acute leukemia

Summary For more than a decade clinical trials have attempted to define the role of immunotherapy in the treatment of patients with acute leukemia. Based on animal studies which indicated that non-specific immune stimulation had an antitumor effect if the tumor burden was small, the use of immunotherapy during remission in patients with acute leukemia seemed appropriate following the initial report of the success of bacillus Calmette-Guerin (BCG) in prolonging remission duration and survival in acute lymphoblastic leukemia. Therefore a series of randomized clinical trials was initiated to confirm these original observations. In four studies comparing BCG inoculations, with or without allogeneic leukemia cells, and chemotherapy or no therapy, no advantage of immunotherapy was noted. Immunotherapy appeared to be equally as good as chemotherapy. A combination of BCG and chemotherapy showed some advantage in one study, but no advantage was noted in two other studies.In acute myeloblastic leukemia several randomized trials suggested that BCG or one of its derivatives when given alone, in combination with allogeneic cells, or with chemotherapy had a marginal effect in prolonging remission duration and survival when compared to chemotherapy or rno therapy.In conclusion, immunotherapy during remission has marginal activity in acute leukemia.     

Randomized trials of high dose chemotherapy for breast cancer

'Now is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning'Winston Churchill in a speech to the Canadian Senate and House of Commons, December 30, 1941. In laboratory models of cancer, dose of cytotoxic chemotherapy correlates with curative therapy, while cumulative dose is associated with longer survival for those who are not cured. These observations suggests a strategy of using high doses when cure is the objective but smaller doses over a prolonged period when palliation and survival are the goal. A strategy combining repetitive cycles of higher doses of cytotoxic therapy, followed by the optimal combination of hormonal and biological agents based on the tumor's receptors might contribute to both the highest possible cure rate and the longest survival.The development of bone marrow transplant (BMT) for leukemias, and its subsequent modification for support after high dose therapy for other malignancies, has a long, complex and emotional history in medicine. At least partly because of firmly held opinions and the way large randomized trials are funded in the United States, few American randomized trials of BMT or high dose therapy strategies have been completed. The vast majority of published randomized BMT and high dose studies are European.Interestingly, in contrast, two large American randomized trials of high dose chemotherapy for breast cancer had actually completed accrual. Accrual on a third was on target until the presentation of five very small or very early randomized trials at the American Society of Clinical Oncology meeting in May of 1999. Results from some of these trials, which were analyzed after a relatively brief follow-up, are too premature to allow definitive conclusions. Nevertheless, these data have been over and misinterpreted within the scientific and lay communities. The remaining studies included a limited number of patients, thus restricting the statistical power of the observations.The desire for quick answers impeded dispassionate analysis of the available data. The opportunity for collegial review of the data further deteriorated with another round of press coverage when the data from the South African adjuvant study were found to be unreliable. Rather than increasing commitment to accrual on randomized and appropriate pilot trials, accrual to the only large American study in existence at that time trickled to a halt.In response to press coverage, Susan Edmonds from the Fred Hutchinson Cancer Research Center observed that 'the NYT article tends to cast shadows generally on the therapy and those providing the therapy rather than pointing out early in the article (where the public will readily see it) that there are a number of very credible research institutions conducting research directed at breast cancer, some looking at high dose chemotherapy and stem cell transplantation.' Dr. Rodenhuis, presenting the large positive Dutch Randomized study (funded by the Dutch insurance industry) at ASCO in 2000, commented on the 'unreasonably high expectations until 1999' and 'unreasonably negative [opinion-ed] since 1999' for high dose adjuvant chemotherapy for breast cancer.     

Breast cancer local recurrence under the form of inflammatory carcinoma,treated with concurrent radiation and chemotherapy,a case report

The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor.There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable “loco regional rescue therapy” to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted.     

High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation for the treatment of solid tumors in adults: a critical review

High-dose chemotherapy (HDCT) plus autologous hematopoietic stem-cell transplantation (HSCT) has been explored in several solid tumors in the attempt to prevent and/or overcome tumor-cell chemo-resistance, based on in vitro evidence of a "dose-response" effect. Preliminary encouraging results from non-randomized trials, led to an increased use of this strategy in the 1990s. Since the end of the nineties, the fraudulent nature of initial reports in breast cancer, the failure of positive prospective randomized trials, HDCT-related toxicities, determined a dramatic decline of interest in this approach. Loss of accrual in ongoing randomized studies was the first consequence, causing the current unavailability of optimal information. From the review of available published data, the use of HDCT with autologous HSCT may improve tumor response rates and/or possibly progression-free survival, especially in some selected patient subgroups. However, this strategy did not demonstrate in almost all cases to produce significantly higher cure rates than standard-dose chemotherapy. Well-designed randomized studies and future strategies integrating HDCT with concomitant and/or subsequent anti-tumor therapies targeted against the residual disease might be suggested in clinically and biologically selected patients.     

Total neoadjuvant treatment in locally advanced rectal cancer

Locally advanced rectal cancer requires a multidisciplinary management, traditionally based on neo-adjuvant (chemo) radiotherapy, conservative surgery with total mesorectal excision and adjuvant chemotherapy. Despite effective in term of local control, this strategy is linked to a high risk of distant metastasis (up to 30%). In this context, recent published randomized phase III clinical trials have tested the potential benefits with a different sequencing and/or intensification of the standard components of the trimodal therapy.Here, we briefly assess the efficacy and discuss the clinical relevance of total neoadjuvant treatment with a focus on indications and results in the short-course radiotherapy followed by chemotherapy use for this setting of patients. Long term results and additional prospective studies are necessary to more accurately estimate the clinical benefit and further establish the role of total neoadjuvant therapy in locally advanced rectal cancer disease.     

The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis

Background

The combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.

Methods

EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.

Results

A total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98–1.12; TTP: HR = 0.94, 95%CI = 0.89–1.00; ORR: RR = 1.07, 95%CI = 0.98–1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83–1.46; PFS: HR = 0.86, 95% CI = 0.67–1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10–1.79) and rash (RR = 7.43, 95% CI = 4.56–12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25–35.93) and fatigue (RR = 9.60, 95% CI = 2.28–40.86) compared with EGFR TKI monotherapy.

Conclusions

The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.     

Hypofractionated radiation therapy for early breast cancer: Follow up of a new treatment standard

AimTo assess the oncological outcomes of patients with early breast cancer treated with breast-conserving surgery and adjuvant hypofractionated radiation therapy.Methods and MaterialThis retrospective analysis included all patients ≥50 year of age with T1-2 N0 M0 breast cancer treated at our Radiation Oncology Unit between 2008 and 2011. Whole-breast radiation therapy was delivered to a dose of 42.5 Gy in 16 fractions, without boost. The primary outcome was local control.Results212 patients were identified. With a median follow up of 60 months, we found 3% local recurrence and 5.3% regional and/or distant recurrences. At the moment of data analysis, 17 patients had died. Out of 5 local recurrences, 2 had previously had a distant recurrence, both of them died. The other three were still alive at the last follow up. These results are comparable to those observed in Phase III trials that use this fractionation scheme.ConclusionsThe results obtained with this retrospective analysis are comparable to those obtained in large randomized trials. This data also supports the use of hypofractionated radiation therapy in Latin America. Hypofractionated radiation therapy for early breast cancer patients should be the standard adjuvant treatment.     

同步放化疗联合深部热疗治疗中晚期宫颈癌的临床疗效观察

目的观察放化疗联合深部热疗治疗中晚期宫颈癌的临床疗效及不良反应。方法选取本院收治的Ⅱb—Ⅲb期宫颈癌患者70例,分为同步放化疗联合深部热疗组（试验组）和同步放化疗组（对照组）,对照组进行根治性放射治疗,放疗第1天开始行化疗,顺铂40mg静脉滴注1d,化疗6个周期,每周重复。试验组：放化疗方法同对照组,于化疗当天行盆腹腔深部热疗（HG-2000体外高频热疗机）,每次热疗60min,每周1次,共4次。于热疗后1h内行放射治疗。结果两组局部肿瘤消退情况、近期疗效、肿瘤局部控制情况、1年期无瘤生存情况比较,差异有统计（P〈0．05）。两组不良反应比较无统计差异。结论同步放化疗联合深部热疗可以提高患者近期疗效,且无严重的并发症,是中晚期宫颈癌治疗中的一种安全有效的模式,值得进一步研究。     

Esophageal cytology in patients receiving cytotoxic drug therapy

Our experience with the cytology of esophageal brush specimens from patients who did not have either gastric or esophageal cancer but who received a variety of chemotherapeutic agents is reported. Ten patients received chemotherapy alone, and nine received combined chemotherapy and radiation therapy. Of the ten patients, three showed evidence of moderate to severe epithelial atypia, which was not seen in the combined treatment group or the control group. The cytologic atypias in the three patients consisted of variation in nuclear size with crowding and overlapping, an increased nuclear-cytoplasmic ratio and multiple nucleoli, many of which varied in size and shape. There was also evidence of cell death and keratinization. Although these patients had not been irradiated, other striking changes were similar to those seen following radiation therapy. The cytologic changes reported here pose a serious diagnostic problem because they may be so severe as to mimic malignant transformation. Evidence of infection by herpes simplex alone or herpes simplex associated with Candida was seen in 32% of the treated patients and in 4% of the control group.     

康莱特注射液联合放化疗治疗中晚期宫颈癌的临床研究

目的：探讨康莱特注射液联合放化疗对中晚期宫颈癌患者的疗效及对放化疗引起的毒副反应的影响。方法：选取2009年6月—2012年3月间笔者所在医院收治的经病理组织学确诊的62例局部晚期宫颈鳞癌患者,随机平均分成实验组（n=31）和对照组（n=31）,分别接受康莱特注射液+放化疗联用和单纯放化疗的治疗,考察两组受试者的临床有效率、生活质量及毒副反应。结果：实验组和对照组受试者的总有效率分别为93.6%和83.9%,无显著差异（P>0.05）;生活质量稳定和改善的比率分别为93.5%和71.0%,有显著差异（P<0.05）;实验组受试者的主要毒副反应发生率明显低于对照组（P<0.05）。结论：康莱特注射液联合放化疗能有效用于中晚期宫颈癌患者的治疗,并显著提高患者生活质量,明显减轻放化疗所致不良反应。     

Controversies in the management of advanced non-small cell lung cancer: maintenance therapy

The majority of patients with non-small cell lung (NSCLC) present with advanced, metastatic disease at the time of diagnosis. The current state of the art for the management of this condition is first- and second-line chemotherapy (CT), along with appropriate supporting care measures, which are supposed to alleviate symptoms and to improve survival. During the last years, maintenance therapy (MT) was included in the therapeutic algorithm for these patients. MT could be defined as continuation of an active treatment until disease progression in patients who demonstrated a non-progressing status following induction chemotherapy. Despite the results of several randomized trials showing a significant benefit by using this approach, the strategy is far from being universally accepted. The internationally recognized guidelines provide different recommendation when it comes to this topic, while some major drawbacks in the design of the positive clinical trials may have distorted the relevance of the communicated data. This paper aimed to review the most contentious aspects which should be considered while contemplating the use of MT in the daily clinical practice.     

National Surgical Breast Project

For public and professional acceptance, clinical studies in breast cancer must be scientifically necessary and ethically justifiable. To resolve controversy based upon retrospective data, they must be prospective and randomized. These guidelines have been used by the National Surgical Adjuvant Breast Project in its investigations carried out during the past 15 years in numerous cooperating institutions. Neither thio-tepa adjuvant to radical mastectomy, nor prophylactic oophorectomy, nor post-operative radiation therapy were found to prolong life. Therefore, prophylactic oophorectomy is contraindicated and adjuvant chemotherapy cannot be justified except perhaps under special circumstances and as part of carefully controlled clinical trials. Postoperative radiation therapy, even in the presence of positive axillary lymph nodes, cannot be recommended except to minimize the rate of local skin recurrences.The present study addresses itself to the timely controversy surrounding proper management of axillary lymph nodes in primary breast cancer. Does removing them alter the outcome of therapy? Total (simple) mastectomy is being compared with radical mastectomy. Women with clinically negative nodes on physical examination are treated either by total (simple) mastectomy alone or by total mastectomy plus radiation, or by radical mastectomy. When the nodes are clinically positive, either radical mastectomy or total mastectomy followed by radiation is being used.The protocol, now underway more than a year, has been well accepted by patients and by many well informed physicians and surgeons. In years ahead it will provide objective evidence as to whether or not removal of the axillary lymph nodes alters the therapeutic efficacy of mastectomy in the treatment of primary breast cancer.     

Combined resynchronisation and implantable defibrillator therapy in left ventricular dysfunction: Bayesian network meta-analysis of randomised controlled trials

Objective To review the evidence base from randomised controlled trials of combined cardiac resynchronisation therapy and implantable cardioverter defibrillator therapy in left ventricular impairment and symptomatic heart failure.Design Bayesian network meta-analysis.Data sources Medline, Embase, and Cochrane databases up to June 2006.Review methods Two reviewers independently assessed trial eligibility and quality. Included trials compared cardiac resynchronisation therapy, implantable cardioverter defibrillator therapy, combined resynchronisation and implantable defibrillator therapy, and medical therapy alone, in patients with impaired left ventricular systolic function. Bayesian random effects network models were used to examine overall number of deaths.Results 12 studies including 1636 events in 8307 patients were identified. Combined cardiac resynchronisation and implantable cardioverter defibrillator therapy reduced the number of deaths by one third compared with medical therapy alone (odds ratio 0.57, 95% credible interval 0.40 to 0.80) but did not further improve survival when compared with implantable defibrillator therapy (0.82, 0.57 to 1.18) or resynchronisation (0.85, 0.60 to 1.22) therapy alone.Conclusion Evidence from randomised controlled trials is insufficient to show the superiority of combined cardiac resynchronisation and implantable cardioverter defibrillator therapy over cardiac resynchronisation therapy alone in patients with left ventricular impairment.     

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions

BackgroundA large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of “positive” results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified.MethodsCINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses.Results108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases.ConclusionsThe proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.