abstract: Cochrane review - Optimal primary surgical treatment for advanced epithelial ovarian cancer

Abstract

BACKGROUND:

Ovarian cancer is the sixth most common cancer among women. In addition to diagnosis and staging, primary surgery is performed to achieve optimal cytoreduction (surgical efforts aimed at removing the bulk of the tumour) as the amount of residual tumour is one of the most important prognostic factors for survival of women with epithelial ovarian cancer. An optimal outcome of cytoreductive surgery remains a subject of controversy to many practising gynae-oncologists. The Gynaecologic Oncology group (GOG) currently defines 'optimal' as having residual tumour nodules each measuring 1 cm or less in maximum diameter, with complete cytoreduction (microscopic disease) being the ideal surgical outcome. Although the size of residual tumour masses after surgery has been shown to be an important prognostic factor for advanced ovarian cancer, it is unclear whether it is the surgical procedure that is directly responsible for the superior outcome that is associated with less residual disease.

OBJECTIVES:

To evaluate the effectiveness and safety of optimal primary cytoreductive surgery for women with surgically staged advanced epithelial ovarian cancer (stages III and IV).To assess the impact of various residual tumour sizes, over a range between zero and 2 cm, on overall survival.

MAIN RESULTS:

There were no RCTs or prospective non-RCTs identified that were designed to evaluate the effectiveness of surgery when performed as a primary procedure in advanced stage ovarian cancer.We found 11 retrospective studies that included a multivariate analysis that met our inclusion criteria. Analyses showed the prognostic importance of complete cytoreduction, where the residual disease was microscopic that is no visible disease, as overall (OS) and progression-free survival (PFS) were significantly prolonged in these groups of women. PFS was not reported in all of the studies but was sufficiently documented to allow firm conclusions to be drawn.When we compared suboptimal (> 1 cm) versus optimal (< 1 cm) cytoreduction the survival estimates were attenuated but remained statistically significant in favour of the lower volume disease group There was no significant difference in OS and only a borderline difference in PFS when residual disease of > 2 cm and < 2 cm were compared (hazard ratio (HR) 1.65, 95% CI 0.82 to 3.31; and HR 1.27, 95% CI 1.00 to 1.61, P = 0.05 for OS and PFS respectively).There was a high risk of bias due to the retrospective nature of these studies where, despite statistical adjustment for important prognostic factors, selection bias was still likely to be of particular concern. Adverse events, quality of life (QoL) and cost-effectiveness were not reported by treatment arm or to a satisfactory level in any of the studies.

AUTHORS' CONCLUSIONS:

During primary surgery for advanced stage epithelial ovarian cancer all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (< 1 cm) residual disease. Due to the high risk of bias in the current evidence, randomised controlled trials should be performed to determine whether it is the surgical intervention or patient-related and disease-related factors that are associated with the improved survival in these groups of women. The findings of this review that women with residual disease < 1 cm still do better than women with residual disease > 1 cm should prompt the surgical community to retain this category and consider re-defining it as 'near optimal' cytoreduction, reserving the term 'suboptimal' cytoreduction to cases where the residual disease is > 1 cm (optimal/near optimal/suboptimal instead of complete/optimal/suboptima

Missing link: inflammation and ovarian cancer : The Lancet Oncology (commentary) - note photo in article

Note: view excellent photo (in blue/not teal) at the end of the article

LIFE Before Death : The Lancet Oncology - documentary/commentary

Genesis of the LIFE Before Death project lay in remarks from WHO. “The project co-producer Mike Hill and I read a 2009 WHO statement saying that 600 million people worldwide were going to suffer in their lifetime from untreated pain due to a lack of access to medicinal opiates”, explains Australian documentary maker Sue Collins. “We found that a very alarming statistic”, she added. Here are three more alarming statistics: more than 5 billion people worldwide have no access to essential pain medicines; this year 3·6 million people will die with untreated severe pain from cancer and AIDS; and 99·9% of these deaths will be in low-income and middle-income countries.

US physician whistleblowers face intimidation and retaliation : The Lancet Oncology

Note: partial summary/pay-per-view article "Reporting of billing fraud or drug company kickbacks is safe, and sometimes even lucrative, for US clinicians. But according to clinicians and advocates, physicians who voice concern about patient care routinely face institutional retaliation. “Blacklisting is more aggressive in the medical profession than any other industry”, says Tom Devine (Government Accountability Project, Washington, DC, USA). Although the Whistleblower Protection Act should protect federal physicians and other government ...

The predicted truncation from a (ovarian) cancer-associated variant of the MSH2 initiation codon alters activity of the MSH2-MSH6 mismatch repair complex

Abstract

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. MMR recognizes and repairs DNA mismatches and small insertion/deletion loops. Carriers of MMR gene variants have a high risk of developing colorectal, endometrial, ovarian, and other extracolonic carcinomas. We report on an ovarian cancer patient who carries a germline MSH2 c.1A>C variant which alters the translation initiation codon. Mutations affecting the MSH2 start codon have been described previously for LS-related malignancies. However, the patients often lack a clear family history indicative of LS and their tumors often fail to display microsatellite instability, a hallmark feature of LS...."(technical)