How many cervical cancer cases can potentially be prevented using a more sensitive screening test at young age?

The human papilloma virus (HPV) DNA test has higher sensitivity than cytology for cervical cancer screening. Therefore, cervical cancer cases that are missed by cytology could potentially be identified if we use primary HPV testing. Studies showed that HPV screening is the preferred primary test at age 35 and over. Given the high prevalence of harmless HPV infections, the use of HPV testing at younger age is less obvious. The number of cancers in young age is often mentioned to indicate the possible benefits of a more sensitive test. We actually estimated the proportion of those cases that is potentially preventable in The Netherlands by the use of a more sensitive screen‐test at the first screening age 30, given that the more sensitive test is used at age 35 and over. We analysed the screening history of women diagnosed with cervical cancer in the period 2004 to March 2009, using data from the Dutch National Pathology Registry. Only 15–30% (two to four cases per 100,000 women) of the cases was preceded by negative cytology under age 35 and therefore could have been prevented by a more sensitive test at age 30. The lower the screening coverage and the shorter the screening interval in those screened at young age, the smaller the gain of a more sensitive test. So, as long as the current screening pattern is not changed, the majority of the cervical cancer cases at young age would still occur even when applying a more sensitive test at the younger ages.     

Sentinel lymph node biopsy for breast cancer: How many nodes are enough?

INTRODUCTION: Sentinel lymph node (SLN) biopsy using blue dye and radioisotope often results in the removal of multiple SLNs. We sought to determine whether there is a point where the surgeon can terminate the procedure without sacrificing accuracy. METHODS: One thousand one hundred ninety-seven patients from University of Michigan and the Mayo Clinic undergoing SLN biopsy formed the study population. Surgeons removed all SLNs until counts within the axilla were less than 10% of the highest node ex vivo and recorded the order in which they were removed. RESULTS: The mean number of SLNs removed per patient was 2.5 (range 1-9). Approximately 42% of patients had three or more lymph nodes removed, while 19% had four or more lymph nodes removed. Eighteen percent of patients (132/725) at University of Michigan and 22% (103/472) at Mayo Clinic had a positive SLN. Ninety-eight percent (231/235) of patients with lymph node metastases were identified by the 3rd SLN while 100% were identified by the 4th SLN. CONCLUSION: Among patients undergoing SLN biopsy for breast cancer, the only positive SLN is rarely identified in the 4th or higher node. Terminating the procedure at the 4th node may lower the cost of the procedure and reduce morbidity.     

How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer?

BACKGROUND.: It remains unclear how many sentinel lymph nodes (SLNs) must be removed to accurately predict lymph node status during SLN dissection in breast cancer. The objective of this study was to determine how many SLNs need to be removed for accurate lymph node staging and which patient and tumor characteristics influence this number. METHODS.: The authors reviewed data for all patients in their prospective database with clinical tumor, lymph node, metastasis (TNM) T1 through T3, N0, M0 breast cancer who underwent lymphatic mapping at their institution during the years 1994 through 2006. There were 777 patients who had at least 1 SLN that was positive for cancer. Simple and multiple quantile regression analyses were used to determine which patient and tumor characteristics were associated with the number of positive SLNs. The baseline number of SLNs that needed to be dissected for detection of 99% of positive SLNs in the total group of patients also was determined. RESULTS.: The mean number of SLNs removed in the 777 lymph node-positive patients was 2.9 (range, 1-13 SLNs). Greater than 99% of positive SLNs were identified in the first 5 lymph nodes removed. On univariate analysis, tumor histology, patient race, tumor location, and tumor size significantly affected the number of SLNs that needed to be removed to identify 99% of all positive SLNs. On multivariate analysis, mixed ductal and lobular histology, Caucasian race, inner quadrant tumor location, and T1 tumor classification significantly increased the number of SLNs that needed to be removed to achieve 99% recovery of all positive SLNs. CONCLUSIONS.: In general, the removal of a maximum of 5 SLNs at surgery allowed for the recovery of >99% of positive SLNs in patients with breast cancer. The current findings indicated that tumor histology, patient race, and tumor size and location may influence this number.     

How relevant are cytokines in colorectal cancer wasting?

PURPOSE: The purpose of this article was to investigate the influence of inflammatory cytokines, pro-cachectic (interleukin [IL]-1 receptor agonist [IL-1ra], IL-6, and tumor necrosis factor-alpha [TNF-alpha]), immunomodulatory (IL-10 and interferon-gamma [IFN-gamma]), and pro-angiogenic (vascular endothelial growth factor [VEGF]), on resting energy expenditure (REE), weight, and nutritional intake and to explore potential interactions between their circulating concentrations and colorectal cancer stage/histologic differentiation and response to radiotherapy (RT). PATIENTS AND METHODS: This was a prospective longitudinal study in 101 patients evaluated before and after neoadjuvant RT, including REE (indirect calorimetry), percent weight loss, usual/current diet (diet history and 24-hour recall), serum concentrations of cytokines (enzyme-linked immunosorbent assay), and RT response. RESULTS: Stages III/IV were often associated with histologic grades 2/3 (P < 0.01), albeit both characteristics independently were associated with higher concentrations of IL-1ra (P /=5%, and intake reduction >/=25% were associated with advanced stage, histologic grades 2/3, higher IL-1ra, IL-6, TNF-alpha, IFN-gamma, and VEGF, and nonresponse to RT (P = 0.003). A general linear model analysis showed that stages III/IV, histologic grades 2/3, and higher IL-1ra, IL-6, TNF-alpha, IFN-gamma, and VEGF were major determinants of REE increase, weight loss, and intake reduction. In predictive value analyses, higher baseline pro-cachectic cytokines (IL-1ra + IL-6 + TNF-alpha) by themselves predicted increased REE (hazard ratio [HR]: 8.25; 95% CI: 2.74-26.47; P < 0.002), greater weight loss (HR: 8.15; 95% CI: 2.22-25.40; P < 0.002), and intake reductions (HR: 7.15; 95% CI: 2.25-16.11; P < 0.004) after RT. CONCLUSION: This study confirms the fact that wasting in colorectal cancer is correlated with tumor burden and histologic aggressiveness and suggests that both characteristics lead to overproduction of IFN-gamma, VEGF, and pro-cachectic cytokines, all of which may cause higher metabolic rates, poor intake, and nonresponse to RT.     

Breast cancer in young women and prognosis: How important are proliferation markers?

AimCompared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.MethodsDistant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.ResultsYoung women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR− tumours (hazard ratio [HR] 0.47 [0.24–0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22–4.50]). Young women with luminal B PR− tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17–17.6]).ConclusionsThe higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.     

How useful are unconventional cancer treatments?

Unconventional cancer treatments are used frequently. Therefore, oncologists need to know about them. This article gives an overview of current knowledge on the most prevalent complementary or alternative cancer therapies. A distinction is made between alleged cures, preventive and adjunctive measures. Shark cartilage, mistletoe, thymus therapy, essiac, hydrazine sulphate, 714-X, dietary regimens, green tea and Panax ginseng are all covered specifically. None of these treatments offer reasonable hope for a cure. Some strategies are promising in terms of cancer prevention. The true potential of unconventional therapies might lie in adjunctive and palliative care. It is concluded that good evidence in this area is scarce. Vis-à-vis the high prevalence of unconventional cancer treatments, rigorous investigations are mandatory, not least for increasing the safety of future patients.     

How are symptoms of ovarian cancer managed?

BACKGROUND:

A study was undertaken to identify the diagnostic approaches that primary care physicians and gynecologists undertake in women with symptoms associated with ovarian cancer.

METHODS:

A vignette‐based survey was mailed to 3200 primary care physicians from the American Medical Association Physician Masterfile. The vignette described a 55‐year‐old woman with symptoms associated with ovarian cancer, although ovarian cancer was never mentioned. The authors evaluated patient, physician, and practice characteristics associated with a workup that could detect ovarian cancer.

RESULTS:

The survey response rate was 61.7%. After exclusions, 1532 physicians were included. Overall, 89.5% of physicians reported that they would recommend testing that can detect ovarian cancer (71.2% ultrasound; 25.4% pelvic computed tomography; 26.5% CA125). In adjusted analysis, the only patient factor associated with ovarian cancer testing was symptom type, genitourinary versus gastrointestinal (risk ratio, 1.07; 95% confidence interval, 1.03‐1.11). Physician and practice characteristics associated with recommending of ovarian cancer testing included specialty (gynecologists > family physicians and internists); type of practice (group > solo); clinical teaching (yes > no); and within Census division, location of practice, with all Central (East, West, North, and South) and Atlantic (Middle and South) areas having a lower likelihood than New England.

CONCLUSIONS:

On the basis of a vignette in which a woman reported symptoms associated with ovarian cancer, the majority of primary care physicians and gynecologists would not recommend CA125, but would recommend imaging of the pelvis. Gynecologists, physicians involved with clinical teaching, and those in group practices were significantly more likely to recommend testing that could lead to an ovarian cancer diagnosis. Cancer 2011;. © 2011 American Cancer Society.     

How many deaths would be avoidable if socioeconomic inequalities in cancer survival in England were eliminated? A national population-based study, 1996–2006

AimInequalities in survival between rich and poor have been reported for most adult cancers in England. This study aims to quantify the public health impact of these inequalities by estimating the number of cancer-related deaths that would be avoidable if all patients were to have the same cancer survival as the most affluent patients.MethodsNational Cancer Registry data for all adults diagnosed with one of 21 common cancers in England were used to estimate relative survival. We estimated the number of excess (cancer-related) deaths that would be avoidable within three years after diagnosis if relative survival for patients in all deprivation groups was as high as the most affluent group.ResultsFor patients diagnosed during 2004–2006, 7122 of the 64,940 excess deaths a year (11%) would have been avoidable if three-year survival for all patients had been as high as in the most affluent group. The annual number of avoidable deaths fell from 8435 (13%) a year for patients diagnosed during 1996–2000. Over 60% of the total number of avoidable deaths occurred within six months after diagnosis and approximately 70% occurred in the two most deprived groups.ConclusionThe downward trend in the annual number of avoidable deaths reflects more an improvement in survival in England overall, rather than a narrowing of the deficit in cancer survival between poor and rich. The lack of any substantial change in the percentage of avoidable excess deaths highlights the persistent nature of the deficit in survival between affluent and deprived groups.     

What are safe margins of resection for invasive and in situ breast cancer?

Adequate surgical margins in breast-conserving surgery are an important predictor of local recurrence (LR) rates. The definition of tumor-free margins in National Surgical Adjuvant Breast and Bowel Project (NSABP) trials requires that tumor cells do not touch ink, but subsequent retrospective single-institution studies have suggested that wider margins confer greater protection against LR. Particularly wide margins have been proposed for ductal carcinoma in situ. However, wider margin requirements lead to higher re-excision rates, with attendant economic, psychological, and cosmetic costs, and perhaps increased mastectomy rates. Juxtaposed against these concerns about optimal margin width, a meta-analysis of clinical trials has demonstrated the survival value of minimizing LR. We are therefore at a juncture where a reduction of LR may be achieved by tumor resection with wide margins, but data regarding optimal margin width are conflicting and the risk/benefit balance of tumorectomy with wide margins has not been demonstrated. A randomized trial of reexcision for close margins inserted into trials of systemic therapy could be considered but seems unlikely. Alternatively, detailed longitudinal data need to balance the value and the cost of wide margins. Until better data are available, the desirable margin width will vary depending on individual circumstances, including age, histology, and patient preference.     

How valid are claims for synergy in published clinical studies?

BackgroundClinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies.MethodsWe searched PubMed using the terms ‘synergy’ or ‘synergistic’ and ‘cancer’ to select articles published between 2006 and 2010. Eligible studies were those that referred to synergy in preclinical studies to justify a drug combination evaluated in a clinical trial.ResultsEighty-six clinical articles met eligibility criteria and 132 preclinical articles were cited in them. Most of the clinical studies were phase I (43%) or phase II trials (56%). Appropriate methods to evaluate synergy in preclinical studies included isobologram analysis in 18 studies (13.6%) and median effect in 10 studies (7.6%). Only 26 studies using animal models (39%) attempted to evaluate therapeutic index. There was no association between the result of the clinical trial and the use of an appropriate method to evaluate synergy (P = 0.25, chi-squared test).ConclusionsSynergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles.     

How many prognostically significant grades of prostate carcinoma are there?

Carcinoma of the prostate (CAP) is often graded as well, moderately or poorly differentiated. We identified 74 well differentiated stage A1 CAP, 58 stage D1 CAP with moderately differentiated metastases, 107 moderately differentiated stage D2 CAP, and 53 poorly differentiated stage D2 CAP and divided each group into 3, 4 or 5 histological patterns. We found that each histological pattern within well, moderately and poorly differentiated prostate carcinoma had similar survival rates. These observations suggest that, using Light microscopy, 3 prognostically significant grades of CAP can be identified - well, moderately and poorly differentiated.