Article Title Discrete-choice experiment to analyse preferences for centralizing specialist cancer surgery services
First published online 2018-03-07
Authors L. Vallejo‐Torres, M. Melnychuk, C. Vindrola‐Padros, M. Aitchison, C. S. Clarke, N. J. Fulop, J. Hines, C. Levermore, S. B. Maddineni, C. Perry, K. Pritchard‐Jones, A. I. G. Ramsay, D. C. Shackley, S. Morris
DOI 10.1002/bjs.10761
Abstract
Background
Centralizing specialist cancer surgery services aims to reduce variations in quality of care and improve patient outcomes, but increases travel demands on patients and families. This study aimed to evaluate preferences of patients, health professionals and members of the public for the characteristics associated with centralization.
Methods
A discrete-choice experiment was conducted, using paper and electronic surveys. Participants comprised: former and current patients (at any stage of treatment) with prostate, bladder, kidney or oesophagogastric cancer who previously participated in the National Cancer Patient Experience Survey; health professionals with experience of cancer care (11 types including surgeons, nurses and oncologists); and members of the public. Choice scenarios were based on the following attributes: travel time to hospital, risk of serious complications, risk of death, annual number of operations at the centre, access to a specialist multidisciplinary team (MDT) and specialist surgeon cover after surgery.
Results
Responses were obtained from 444 individuals (206 patients, 111 health professionals and 127 members of the public). The response rate was 52·8 per cent for the patient sample; it was unknown for the other groups as the survey was distributed via multiple overlapping methods. Preferences were particularly influenced by risk of complications, risk of death and access to a specialist MDT. Participants were willing to travel, on average, 75 min longer in order to reduce their risk of complications by 1 per cent, and over 5 h longer to reduce risk of death by 1 per cent. Findings were similar across groups.
Conclusion
Respondents' preferences in this selected sample were consistent with centralization.
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Ideal
surgical treatment for acute duodenal injuries should offer a
definitive treatment, with low morbidity and mortality. It should be
simple and easily reproducible by acute care surgeons in an emergency.
Duodenal injury, due to major perforated or bleeding peptic ulcers or
iatrogenic/traumatic perforation, represents a surgical challenge, with
high morbidity and mortality. The aim was to review definitive surgery
with pancreas‐sparing, ampulla‐preserving duodenectomy for these
patients.
Method
Pancreas‐sparing,
ampulla‐preserving D1–D2 duodenectomy was used for patients presenting
with major duodenal injuries over a 5‐year interval. The ampulla was
identified and preserved using a transcystic/transpapillary tube. The
outcomes were recorded.
Results
Ten
patients were treated with this technique; seven had perforated or
bleeding peptic ulcers, two had iatrogenic perforations and one blunt
abdominal trauma. Their mean age was 78 (range 65–84) years. Four
patients were haemodynamically unstable. The location of the duodenal
injury was always D1 and/or D2, above or in close proximity to the
ampulla of Vater. The surgical approach was open in nine patients and
laparoscopic in one. The mean duration of surgery was 264 (range
170–377) min. All patients were transferred to the ICU after surgery
(mean ICU stay 4·4 (range 1–11) days), and the overall mean hospital
stay was 17·8 (range 10–32) days. Six patients developed major
postoperative complications: cardiorespiratory failure in five and
gastrointestinal complications in four. Surgical reoperation was needed
in one patient for postoperative necrotizing and bleeding pancreatitis.
Two patients died from their complications.
Conclusion
Pancreas‐sparing,
ampulla‐preserving D1–D2 duodenectomy for emergency treatment of major
duodenal perforations is feasible and associated with satisfactory
outcomes.
BJS 2018;
105: 1487-1492.
Published: 19th July 2018
Authors: S. Di Saverio, E. Segalini, A. Birindelli, S. Todero, M. Podda, A. Rizzuto et al.
Authors: P. Probst, S. Haller, T. Bruckner, A. Ulrich, O. Strobel, T. Hackert et al.
Background
Preoperative nutritional status has an impact on patients' clinical outcome. For pancreatic surgery, however, it is unclear which nutritional assessment scores adequately assess malnutrition associated with postoperative outcome.
Method
Patients scheduled for elective pancreatic surgery at the University of Heidelberg were screened for eligibility. Twelve nutritional assessment scores were calculated before operation, and patients were categorized as either at risk or not at risk for malnutrition by each score. The postoperative course was monitored prospectively by assessors blinded to the nutritional status. The primary endpoint was major complications evaluated for each score in a multivariable analysis corrected for known risk factors in pancreatic surgery.
Results
Overall, 279 patients were analysed. A major complication occurred in 61 patients (21·9 per cent). The proportion of malnourished patients differed greatly among the scores, from 1·1 per cent (Nutritional Risk Index) to 79·6 per cent (Nutritional Risk Classification). In the multivariable analysis, only raised amylase level in drainage fluid on postoperative day 1 (odds ratio (OR) 4·91, 95 per cent c.i. 1·10 to 21·84; P = 0·037) and age (OR 1·05, 1·02 to 1·09; P = 0·005) were significantly associated with major complications; none of the scores was associated with, or predicted, postoperative complications.
Conclusion
None of the nutritional assessment scores defined malnutrition relevant to complications after pancreatic surgery and these scores may thus be abandoned.
Author: H. S. Patel, A. R. Silver, T. Levine, G. Williams, J. M. Northover
Published: Aug 20, 2010
Pages: 1716-1721
DOI: 10.1002/bjs.7218
Abstract
Background:
Immunosuppression is a known risk factor for anal human
papillomavirus (HPV) disease, including anal squamous cell carcinoma.
Additional risk factors for HPV‐related disease have not
been studied in the renal transplant population. The demographics
of anal HPV and associated risk factors were investigated
in this population.
Methods:
Anal cytology and polymerase chain reaction were used to
assess anal HPV disease in a cohort of transplant recipients at the
Royal London Hospital. Risk factors associated with
increased immunosuppression and HPV exposure were collated to determine
any association with anal disease.
Results:
Anal dysplasia was associated with anal oncogenic HPV infection (P < 0·001), duration of immunosuppression (P = 0·050), previous genital warts (P = 0·018) and receptive anal intercourse (P = 0·013).
Author: P. Renzulli, T. Gross, B. Schnüriger, A. M. Schoepfer, D. Inderbitzin, A. K. Exadaktylos, H. Hoppe, D. Candinas
Published: Aug 26, 2010
Pages: 1696-1703
DOI: 10.1002/bjs.7203
Abstract
Background:
Non‐operative management (NOM) of blunt splenic injuries is nowadays considered the standard treatment. The present study
identified selection criteria for primary operative management (OM) and planned NOM.
Methods:
All adult patients with blunt splenic injuries treated at Berne University Hospital, Switzerland, between 2000 and 2008 were
reviewed.
Results:
There were 206 patients (146 men) with a mean(s.d.) age
of 38·2(19·1) years and an Injury Severity Score of 30·9(11·6). The
American Association for the Surgery of Trauma
classification of the splenic injury was grade 1 in 43 patients (20·9
per cent),
grade 2 in 52 (25·2 per cent), grade 3 in 60 (29·1 per
cent), grade 4 in 42 (20·4 per cent) and grade 5 in nine (4·4 per cent).
Forty‐seven patients (22·8 per cent) required immediate
surgery. Transfusion of at least 5 units of red cells (odds ratio
(OR) 13·72, 95 per cent confidence interval 5·08 to
37·01), Glasgow Coma Scale score below 11 (OR 9·88, 1·77 to 55·16) and
age 55 years or more (OR 3·29, 1·07 to 10·08) were
associated with primary OM. The rate of primary OM decreased from 33·3
to 11·9 per cent after the introduction of transcatheter
arterial embolization in 2005. Overall, 159 patients (77·2 per cent)
qualified for NOM, which was successful in 143 (89·9 per
cent). The splenic salvage rate was 69·4 per cent. In multivariable
analysis age at least 40 years was the only factor
independently related to failure of NOM (OR 13·58, 2·76 to 66·71).
Author: K. B. Clough, R. Nasr, C. Nos, M. Vieira, C. Inguenault, B. Poulet
Published: Aug 26, 2010
Pages: 1659-1665
DOI: 10.1002/bjs.7217
Abstract
Background:
The exact anatomical location of the sentinel lymph node
(SLN) in the axilla has not ascertained clinically, but could be
useful both for teaching purposes and to reduce the
morbidity of SLN biopsy. The aim of the study was to determine the
position
of the SLN in the axilla and to demonstrate that this
location is not random.
Methods:
A consecutive series of 242 patients with stage I breast cancer (T1/T2 N0) or ductal carcinoma in situ
who underwent SLN localization by peritumoral injection were included
in a prospective study to map the location of the SLN
in the axilla. A new anatomical classification of the
lower part of the axilla based on the intersection of two anatomical
landmarks, the lateral thoracic vein (LTV) and the second
intercostobrachial nerve (ICBN), is described. These two constant
elements form the basis of four axillary zones (A, B, C
and D).
Results:
In 98·2 per cent of patients the axillary SLN was located
medially, alongside the LTV, either below the second ICBN (zone
A, 86·8 per cent) or above it (zone B, 11·5 per cent). In
only four patients (1·8 per cent) was the SLN located laterally
in the axilla.
Background
Endovenous ablation techniques and ultrasound‐guided foam sclerotherapy (UGFS) have largely replaced open surgery for treatment of great saphenous varicose veins. This was a randomized trial to compare the effect of surgery, endovenous laser ablation (EVLA) (with phlebectomies) and UGFS on quality of life and the occlusion rate of the great saphenous vein (GSV) 12 months after surgery.
Methods
Patients with symptomatic, uncomplicated varicose veins (CEAP class C2–C4) were examined at baseline, 1 month and 1 year. Before discharge and at 1 week, patients reported a pain score on a visual analogue scale. Preoperative and 1‐year assessments included duplex ultrasound imaging and the Aberdeen Varicose Vein Severity Score (AVVSS).
Results
The study included 214 patients: 65 had surgery, 73 had EVLA and 76 had UGFS. At 1 year, the GSV was occluded or absent in 59 (97 per cent) of 61 patients after surgery, 71 (97 per cent) of 73 after EVLA and 37 (51 per cent) of 72 after UGFS (P < 0·001). The AVVSS improved significantly in comparison with preoperative values in all groups, with no significant differences between them. Perioperative pain was significantly reduced and sick leave shorter after UGFS (mean 1 day) than after EVLA (8 days) and surgery (12 days).
Conclusion In comparison with open surgery and EVLA, UGFS resulted in equivalent improvement in quality of life but significantly higher residual GSV reflux at 12‐month follow‐up.
Author: M. Venermo, J. Saarinen, E. Eskelinen, S. Vähäaho, E. Saarinen, M. Railo, I. Uurto, J. Salenius, A. Albäck, Published: Aug 26, 2016 Pages: 1438-1444 DOI: 10.1002/bjs.10260
Objective: The primary objective of this project was to decrease computed tomography (CT) utilization for the diagnosis of appendicitis in an academic children's hospital emergency department (ED) through a multidisciplinary quality improvement initiative.
Background: Appendicitis is the most common abdominal diagnosis leading to the hospitalization of children in the United States. However, the diagnosis of appendicitis in children can be difficult and many centers rely heavily upon CT scans. Recent recommendations emphasize decreasing CT use among pediatric patients because of an increased lifetime risk of radiation-induced malignancies.
Methods: A retrospective review was conducted of patients diagnosed with appendicitis in the ED at Children's Mercy Hospital from January 1, 2011 to February 28, 2014 to establish a baseline cohort. From August 1, 2014 to July 31, 2015, a newly designed diagnostic algorithm was used in the ED and patients were prospectively followed. Any patient discharged from the ED received a follow-up phone call. Patients treated for appendicitis before and after pathway implementation were compared. In addition, any patient evaluated for appendicitis after implementation of the algorithm was analyzed for adherence to the clinical pathway. Differences between the 2 groups were analyzed using ANOVA, Wilcoxon Rank Sum, χ2, and Fisher Exact tests.
Results: Of 840 patients seen after implementation of the diagnostic algorithm, 267 were diagnosed with appendicitis. After implementation of the algorithm, CT utilization decreased from 75.4% to 24.2% (P < 0.0001) in patients with appendicitis. CT utilization was 27.3% after implementation, regardless of the ultimate diagnosis or algorithm adherence. The diagnostic pathway had a sensitivity of 98.6% and specificity of 94.4%.
Conclusions: Implementation of a diagnostic algorithm for appendicitis in children significantly decreases CT utilization, whereas maintaining a high sensitivity and specificity.journals.lww.com
by
Shah, Sohail R.; Sinclair, Kelly A.; Theut, Stephanie B.; Johnson,
Kathy M.; Holcomb, George W. III; St. Peter, Shawn D. / Today, 5:30 AM
Increasing evidence suggests that diabetes mellitus (DM) is associated with increased cancer incidence and mortality. Several mechanisms involved in diabetes, such as promotion of cell proliferation and decreased apoptosis, may foster carcinogenesis. This study investigated the association between DM and cancer incidence and cancer-specific mortality in patients with breast and colorectal carcinoma.
Methods
A meta-analysis of controlled trials, prospective cohort studies and pooled cohort studies published after 2007 was conducted. Embase, PubMed and the Cochrane Library were searched. Summary hazard ratios (HRs) were calculated using a random-effects model. Sensitivity and subgroup analyses were performed to adjust for confounders, mode of DM assessment and follow-up time.
Results
Twenty studies were included to investigate the association between DM and breast and colorectal cancer incidence and cancer-specific mortality. The studies predominantly comprised patients with type II DM. The overall HR for breast cancer incidence was 1·23 (95 per cent confidence interval 1·12 to 1·34) and that for colorectal cancer was 1·26 (1·14 to 1·40) in patients with DM compared with those without diabetes. The overall HR was 1·38 (1·20 to 1·58) for breast cancer- and 1·30 (1·15 to 1·47) for colorectal cancer-specific mortality in patients with DM compared with those without diabetes.
Conclusion
This meta-analysis indicated that DM is a risk factor for breast and colorectal cancer, and for cancer-specific mortality.
British Journal of Surgery Posted on: Wednesday, September 04, 2013 7:46 PM Author: K. M. J. De Bruijn, L. R. Arends, B. E. Hansen, S. Leeflang, R. Ruiter, C. H. J. van Eijck Subject: Systematic review and meta-analysis of the association between diabetes mellitus and incidence and mortality in breast and colorectal cancer
The aim of this review is to introduce the topic of next-generation DNA sequencing, a new technology that is being introduced into clinical practice, and to explain the potential impact for breast cancer surgeons and the wider breast cancer multidisciplinary team.
Methods
The PubMed database was used to identify relevant studies relating to breast cancer genetics. This evidence was then used to provide context and background information to demonstrate how next-generation sequencing (NGS) might change breast cancer practice.
Results
With NGS, breast cancer clinicians will know whether their patients carry high-risk mutations in genes, such as BRCA1 or BRCA2, before the start of treatment. This could alter treatment decisions; for instance, more women might opt for mastectomy instead of breast-conserving surgery, or for bilateral rather than unilateral surgery.
Conclusion
The introduction of NGS will have a significant impact on breast cancer services in the near future. Speed of testing will improve in regions of the world where NGS is adopted in place of conventional sequencing, and, as costs decrease, genetic testing will also become accessible and realistic in less well funded health economies. This will create opportunities to improve patient treatment and challenges for the breast cancer multidisciplinary team.
British Journal of Surgery Posted on: Thursday, March 27, 2014 6:25 PM Author: S. M. Pilgrim, S. J. Pain, M. D. Tischkowitz Subject: Opportunities and challenges of next-generation DNA sequencing for breast units
Sleeve gastrectomy is being performed increasingly in Europe. Data on long-term outcome would be helpful in defining the role of sleeve gastrectomy. The aim of this study was to evaluate the outcome of sleeve gastrectomy as a primary bariatric procedure.
Methods
Medical charts of all patients who underwent a primary sleeve gastrectomy at the authors' institution between August 2006 and December 2012 were reviewed retrospectively using a prospective online data registry. For evolution of weight loss and co-morbidity, only patients with follow-up of at least 1 year were included. A subgroup analysis was done to compare patients with an intended stand-alone procedure and those with an intended two-stage procedure.
Results
A total of 1041 primary sleeve gastrectomies were performed in the study period. Median duration of surgery was 47 min, and median hospital stay was 2 days. Intra-abdominal bleeding occurred in 27 patients (2·6 per cent) and staple-line leakage in 24 (2·3 per cent). Some 866 patients had at least 1 year of follow-up. Mean excess weight loss was 68·4 per cent after 1 year (P < 0·001) and 67·4 per cent after 2 years. Smaller groups of patients achieved a mean excess weight loss of 69·3 per cent (163 patients), 70·5 per cent (62) and 58·3 per cent (19) after 3, 4 and 5 years respectively. No difference in postoperative complications was found between the subgroups. Seventy-one (8·2 per cent) of 866 patients had a revision of the sleeve gastrectomy; reflux or dysphagia was the indication in 34 (48 per cent) of these patients.
Conclusion
Sleeve gastrectomy is a safe and effective bariatric procedure. Maximum weight loss was achieved after 4 years. Long-term results regarding weight loss and co-morbidities were satisfactory.
British Journal of Surgery Author: P. W. J. van Rutte, J. F. Smulders, J. P. de Zoete, S. W. Nienhuijs Subject: Outcome of sleeve gastrectomy as a primary bariatric procedure
Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroid hormones values. The prevalence of subclinical hypothyroidism is 4% to 8% in the general population, and up to 15% to 18% in women who are over 60 years of age. There is considerable controversy regarding the morbidity, the clinical significance of subclinical hypothyroidism and if these patients should be treated.
Objectives
To assess the effects of thyroid hormone replacement for subclinical hypothyroidism.
Search methods
We searched The Cochrane Library, MEDLINE, EMBASE and LILACS. Ongoing trials databases, reference lists and abstracts of congresses were scrutinized as well.
Selection criteria
All studies had to be randomised controlled trials comparing thyroid hormone replacement with placebo or no treatment in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. We contacted study authors for missing or additional information.
Main results
Twelve trials of six to 14 months duration involving 350 people were included. Eleven trials investigated levothyroxine replacement with placebo, one study compared levothyroxine replacement with no treatment. We did not identify any trial that assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood and quality of life with no statistically significant improvement. One study showed a statistically significant improvement in cognitive function. Six studies assessed serum lipids, there was a trend for reduction in some parameters following levothyroxine replacement. Some echocardiographic parameters improved after levothyroxine replacement therapy, like myocardial relaxation, as indicated by a significant prolongation of the isovolumic relaxation time as well as diastolic dysfunction. Only four studies reported adverse events with no statistically significant differences between groups.
Authors' conclusions
In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups.Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.
Differentiated thyroid carcinoma with thyroglobulin positive and radioactive iodine negative metastases has been observed in follow-up studies. The management of this condition remains controversial. Most studies support blind radioactive iodine treatment while others negate this approach.
Objectives
To assess the effects of radioiodine therapy for differentiated thyroid carcinoma with thyroglobulin positive and radioactive iodine negative metastases.
Search methods
Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library, China National Infrastructure (CNKI) and paper collections of conferences held in Chinese.
Selection criteria
Randomised controlled clinical trials and prospective controlled clinical trials.
Data collection and analysis
Two authors independently extracted data and interviewed authors of all potentially relevant studies by electronic mail to verify randomisation procedures. One author entered data into a data extraction form and the second one verified the results of this procedure.
Main results
Because of the absence of any suitable randomised or prospective controlled trial in this area, results currently cannot be presented.
Authors' conclusions
The currently available evidence is insufficient to reliably assess the potential of radioiodine treatment for differentiated thyroid carcinoma with thyroglobulin positive and radioactive iodine negative metastases.
Several studies have evaluated the clinical effectiveness of endocrine therapy alone in women aged 70 years or over and who are fit for surgery.
Objectives
To identify and review the evidence from randomised trials comparing primary endocrine therapy (endocrine therapy alone) to surgery, with or without adjuvant endocrine therapy, in the management of women aged 70 years or over with operable breast cancer.
Search methods
For this update, the Cochrane Breast Cancer Group Specialised Register was searched 13th November 2007 using the codes for "early breast cancer", "endocrine therapy", "psychosocial" or "surgery".
Selection criteria
Randomised trials comparing primary endocrine therapy with surgery, with or without adjuvant endocrine therapy, in the management of women aged 70 years or over with early breast cancer and who are fit for surgery.
Data collection and analysis
Studies were assessed for eligibility and quality, and data from published trials were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed-effect model was used for meta-analysis. Toxicity and quality-of-life data were extracted, where present. Where outcome data were not available, trialists were contacted and unpublished data requested.
Main results
Seven eligible trials were identified of which six had published time-to-event data and one was published only in abstract form with no usable data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen.
Data, based on an estimated 869 deaths in 1571 women, were unable to show a statistically significant difference in favour of either surgery or primary endocrine therapy in respect of overall survival. However, there was a statistically significant difference in terms of progression-free survival, which favoured surgery with or without endocrine therapy.
The hazard ratios (HR) for overall survival were: 0.98 (95% confidence interval (CI) 0.74 to 1.30, P value 0.9) for surgery alone versus primary endocrine therapy; 0.86 (95% CI 0.73 to 1.00, P value 0.06) for surgery plus endocrine therapy versus primary endocrine therapy. The HRs for progression-free survival were: 0.55 (95% CI 0.39 to 0.77, P value 0.0006) for surgery alone versus primary endocrine therapy; 0.65 (95% CI 0.53 to 0.81, P value 0.0001) for surgery plus endocrine therapy versus primary endocrine therapy (each comparison based on only one trial). Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included paresthesia on the ipsilateral arm and lateral thoracic wall in those who had axillary clearance. One study suggested that those undergoing surgery suffered more psychosocial morbidity at three months postsurgery, although this difference had disappeared by two years.
Authors' conclusions
Primary endocrine therapy should only be offered to women with oestrogen receptor (ER) positive tumours who are unfit for or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.
The majority of women diagnosed with breast cancer undergo a multidisciplinary treatment with surgical intervention and radiotherapy or chemotherapy, or both. The importance of timing of tumour removal in relation to the menstrual cycle and its influence on disease-free survival and overall survival has been studied by researchers since 1989 but still remains speculative.
Objectives
To determine if surgery performed either during the follicular or luteal phase of the menstrual cycle affects the overall and disease-free survival of premenopausal breast cancer patients.
Search methods
We searched the Cochrane Breast Cancer Group Trials Register (January 2009), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 1), MEDLINE (1966 to January 2009), EMBASE (1974 to September 2006) and the WHO International Clinical Trials Registry Platform (ICTRP) search portal (July 2010). We checked references of articles and communicated with authors.
Selection criteria
Randomised controlled trials (RCTs) comparing breast surgery during the follicular phase of the menstrual cycle with the luteal phase in premenopausal women. Prospective non-RCTs or observational studies were considered if randomised studies were lacking.
Data collection and analysis
Three authors independently extracted data and assessed trial quality.
Main results
Completed randomised trials were not found. There is one trial that is currently ongoing in Italy; the results have yet to be published.
Two prospective observational studies had data on recurrence-free survival. One study reported an odds ratio for recurrence rate at one year (where > 1 favours the luteal phase) of 0.86 (95% confidence interval (CI) 0.69 to 1.08); 0.87 at two years (95% CI 0.69 to 1.09); 0.95 at three years (95% CI 0.75 to 1.21); 1.12 at four years (95% CI 0.87 to 1.43); and 1.12 at five years (95% CI 0.87 to 1.43). Another study reported a hazard ratio for overall survival of 1.02 (95% CI 0.995 to 1.04, P = 0.14) and for disease-free survival of 1.00 (95% CI 0.98 to 1.02, P = 0.92) at three years based on the last and first menstrual period. The results were not significant. There was no difference in the recurrence rate whether the surgery was done during the follicular or luteal phase of the menstrual cycle.
Authors' conclusions
In the absence of RCTs, this review provides evidence from large prospective observational studies that timing of surgery does not show a significant effect on survival.
After surgery for localised breast cancer, radiotherapy (RT) improves both local control and breast cancer-specific survival. In patients at risk of harbouring micro-metastatic disease, adjuvant chemotherapy (CT) improves 15-year survival. However, the best sequence of administering these two types of adjuvant therapy for early-stage breast cancer is unclear.
Objectives
To determine the effects of different sequencing of adjuvant CT and RT for women with early breast cancer.
Search methods
An updated search was carried out in the Cochrane Breast Cancer Group's Specialised Register (20 May 2011), MEDLINE (14 December 2011), EMBASE (20 May 2011) and World Health Organization (WHO) International Clinical Trials Registry Platform (20 May 2011). Details of the search strategy and methods of coding for the Specialised Register are described in the Group's module in The Cochrane Library. We extracted studies that had been coded as 'early', 'chemotherapy' and 'radiotherapy'.
Selection criteria
We included randomised controlled trials evaluating different sequencing of CT and RT.
Data collection and analysis
We assessed the eligibility and quality of the identified studies and extracted data from the published reports of the included trials. We derived odds ratios (OR) and hazard ratios (HR) from the available numerical data. Toxicity data were extracted, where reported. We used a fixed-effect model for meta-analysis and conducted analyses on the basis of the method of sequencing of the two treatments.
Main results
Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for local recurrence-free survival, overall survival, relapse-free survival and metastasis-free survival based on 1166 randomised women in three trials. Concurrent chemoradiation increased anaemia (OR 1.54; 95% confidence interval (CI) 1.10 to 2.15), telangiectasia (OR 3.85; 95% CI 1.37 to 10.87) and pigmentation (OR 15.96; 95% CI 2.06 to 123.68). Treated women did not report worse cosmesis with concurrent chemoradiation but physician-reported assessments did (OR 1.14; 95% CI 0.42 to 3.07). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), RT before CT was associated with an increased risk of neutropenic sepsis (OR 2.96; 95% CI 1.26 to 6.98) compared with CT before RT, but other measures of toxicity did not differ.
Authors' conclusions
The data included in this review, from three well-conducted randomised trials, suggest that different methods of sequencing CT and RT do not appear to have a major effect on recurrence or survival for women with breast cancer if RT is commenced within seven months after surgery.
Breast cancer is the most common cause of cancer death in women world wide. In the developed world it is estimated that approximately 1 in 11 women will develop the disease over their lifetime. Most new diagnoses are at an early stage of disease (especially in countries with mammographic screening programs), where all macroscopic evidence of malignancy can be removed, and there is a reasonable prospect of long term survival with standard treatments. However, breast cancer can sometimes present as a mass that is large, diffuse or attached to surrounding tissues, making initial surgery very difficult. Such "locally advanced" breast cancer accounts for between 5-30% of all cases of breast cancer, depending on the population group studied (Therasse 2003).
To date the results of treatment of locally advanced breast cancer have been poor, with 5 year survival rates often as low as 30%. Progress in this area has been limited by the relative infrequency of the disease, and resultant lack of clinical trials evaluating its management (Hortobagyi 1998). Furthermore, the definition of what constitutes "locally advanced breast cancer" is broad, and includes those with inoperable stage IIIB, potentially operable T3 tumours, positive supraclavicular lymphadenopathy and inflammatory subtypes. Thirdly chemotherapy, surgery and radiotherapy have often been used in different combinations and sequences across different treatment centres. This variability in disease definition and treatment strategies makes assessment of efficacy very complex.
The aim of this review is to identify and synthesise data from all published randomized trials that compare the effects of different local and systemic therapies on patient outcomes in women with locally advanced breast cancer.
Objectives
1. To assess the impact of different combinations of local therapies and systemic therapies on survival and locoregional disease control in locally advanced breast cancer.
Specifically, for local therapies, the effect of differing amounts and type of local therapy (surgery and radiotherapy, either alone or in combination) the effect of different sequences of local therapy (surgery then radiotherapy or vice versa)
and for systemic therapies the effect of differing amounts and duration of treatment (for example, more chemotherapy versus less or chemotherapy with or without endocrine therapy) the effect of sequence in relation to local therapy (chemotherapy before or after local therapy)
2. To determine if overall duration or amount of therapy influences treatment outcome
Methods
Criteria for considering studies for this review
Types of studies
Randomized controlled trials involving
women with "locally advanced breast cancer" as classified by the investigators
women with inoperable non-inflammatory breast cancer
women with inflammatory breast cancer as defined by the investigator
Properly randomized controlled trials that evaluate
amount of local therapy (surgery, radiotherapy or both)
amount of systemic therapy (dose, duration, intensity)
sequence of modalities
Local therapies may include surgery and/or radiotherapy. Systemic therapies may include chemotherapy and/or endocrine therapy and/or molecularly targeted therapy. Trials that study a mixed population of women with "early or locally advanced" or "locally advanced or metastatic" disease will be excluded, unless the proportion of patients with locally advanced disease represents the majority (>85%), or patients with locally advanced disease can be identified clearly and outcomes extracted.
Types of participants
Women with "locally advanced breast cancer" as defined above: Any age of patient Any menopausal status Any hormone receptor status (ER or PR) Any Her 2 status
Types of interventions
Interventions include the use of any of:
Surgery
Radiotherapy (in the neoadjuvant, definitive or adjuvant setting, using conventional external beam techniques and including the use of boosts, and dose fractionation)
Chemotherapy (in the neoadjuvant, definitive or adjuvant setting, given systemically, using conventional cytotoxic agents, with or without colony stimulating factors [excluding cytokines or monoclonal antibodies used alone, and high-dose chemotherapy requiring stem cell support])
Local control (proportion free of local disease progression)
Secondary outcomes
Disease free survival
Time to, or proportion with local disease progression
Time to, or proportion with distant disease progression
Response rate
Quality of life
Toxicity
Subgroup analyses Will be performed if there are sufficient data to justify them, in particular to identify differences in the effectiveness of treatments between:
inflammatory and non-inflammatory subtypes
Search methods for identification of studies
The Cochrane Breast Cancer Group's specialized register will be searched. Trials coded as potentially relevant to locally advanced or inflammatory breast cancer will be assessed by both investigators, first by abstract, then blinded methods section then full manuscript as appropriate. Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library.
Data collection and analysis
Study selection
Study selection will be undertaken independently by the reviewers (CM and NW), both of whom are content experts. The above selection criteria will be applied to each trial, initially based on title, with the subsequently agreed pool of potentially eligible trials screened with the results section (and any other area where the results appeared) masked. For unpublished trials, available information from conference proceedings will be screened.
Assessment of trial quality
A quality score will be applied to describe the adequacy of allocation concealment: A. low risk of bias in the randomization process (eg randomization by telephone call to central office). B. moderate risk of bias (eg sealed envelopes) C. high risk of bias D. trials where there was insufficient information to score allocation concealment
Data extraction
Initial data will be extracted independently by CM and NW. This will include baseline characteristics of the patients, the interventions being tested, tumour response rates, median survivals, and information about toxicity and quality of life. Hazard ratios and confidence intervals will be derived by extracting and combining study estimates according to the method described in Parmar 1998.
Analysis
Results of eligible studies will be statistically synthesised (meta-analysis) if appropriate. It is inevitable that some post hoc judgment will be required, because a number of different questions may be posed, and there may only be one or two trials addressing particular questions. Tumour response rates as reported will be analysed as categorical variables and a pooled relative risk derived if appropriate. It is unlikely that anything other than a narrative review of toxicity and quality of life data will be possible.
Background
Breast cancer is the most common cause of cancer death in women world wide. In the developed world it is estimated that approximately 1 in 11 women will develop the disease over their lifetime. Most new diagnoses are at an early stage of disease (especially in countries with mammographic screening programs), where all macroscopic evidence of malignancy can be removed, and there is a reasonable prospect of long term survival with standard treatments. However, breast cancer can sometimes present as a mass that is large, diffuse or attached to surrounding tissues, making initial surgery very difficult. Such "locally advanced" breast cancer accounts for between 5-30% of all cases of breast cancer, depending on the population group studied (Therasse 2003).
To date the results of treatment of locally advanced breast cancer have been poor, with 5 year survival rates often as low as 30%. Progress in this area has been limited by the relative infrequency of the disease, and resultant lack of clinical trials evaluating its management (Hortobagyi 1998). Furthermore, the definition of what constitutes "locally advanced breast cancer" is broad, and includes those with inoperable stage IIIB, potentially operable T3 tumours, positive supraclavicular lymphadenopathy and inflammatory subtypes. Thirdly chemotherapy, surgery and radiotherapy have often been used in different combinations and sequences across different treatment centres. This variability in disease definition and treatment strategies makes assessment of efficacy very complex.
The aim of this review is to identify and synthesise data from all published randomized trials that compare the effects of different local and systemic therapies on patient outcomes in women with locally advanced breast cancer.
Objectives
1. To assess the impact of different combinations of local therapies and systemic therapies on survival and locoregional disease control in locally advanced breast cancer.
Specifically, for local therapies, the effect of differing amounts and type of local therapy (surgery and radiotherapy, either alone or in combination) the effect of different sequences of local therapy (surgery then radiotherapy or vice versa)
and for systemic therapies the effect of differing amounts and duration of treatment (for example, more chemotherapy versus less or chemotherapy with or without endocrine therapy) the effect of sequence in relation to local therapy (chemotherapy before or after local therapy)
2. To determine if overall duration or amount of therapy influences treatment outcome
Methods
Criteria for considering studies for this review
Types of studies
Randomized controlled trials involving
women with "locally advanced breast cancer" as classified by the investigators
women with inoperable non-inflammatory breast cancer
women with inflammatory breast cancer as defined by the investigator
Properly randomized controlled trials that evaluate
amount of local therapy (surgery, radiotherapy or both)
amount of systemic therapy (dose, duration, intensity)
sequence of modalities
Local therapies may include surgery and/or radiotherapy. Systemic therapies may include chemotherapy and/or endocrine therapy and/or molecularly targeted therapy. Trials that study a mixed population of women with "early or locally advanced" or "locally advanced or metastatic" disease will be excluded, unless the proportion of patients with locally advanced disease represents the majority (>85%), or patients with locally advanced disease can be identified clearly and outcomes extracted.
Types of participants
Women with "locally advanced breast cancer" as defined above: Any age of patient Any menopausal status Any hormone receptor status (ER or PR) Any Her 2 status
Types of interventions
Interventions include the use of any of:
Surgery
Radiotherapy (in the neoadjuvant, definitive or adjuvant setting, using conventional external beam techniques and including the use of boosts, and dose fractionation)
Chemotherapy (in the neoadjuvant, definitive or adjuvant setting, given systemically, using conventional cytotoxic agents, with or without colony stimulating factors [excluding cytokines or monoclonal antibodies used alone, and high-dose chemotherapy requiring stem cell support])
Local control (proportion free of local disease progression)
Secondary outcomes
Disease free survival
Time to, or proportion with local disease progression
Time to, or proportion with distant disease progression
Response rate
Quality of life
Toxicity
Subgroup analyses Will be performed if there are sufficient data to justify them, in particular to identify differences in the effectiveness of treatments between:
inflammatory and non-inflammatory subtypes
Search methods for identification of studies
The Cochrane Breast Cancer Group's specialized register will be searched. Trials coded as potentially relevant to locally advanced or inflammatory breast cancer will be assessed by both investigators, first by abstract, then blinded methods section then full manuscript as appropriate. Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library.
Data collection and analysis
Study selection
Study selection will be undertaken independently by the reviewers (CM and NW), both of whom are content experts. The above selection criteria will be applied to each trial, initially based on title, with the subsequently agreed pool of potentially eligible trials screened with the results section (and any other area where the results appeared) masked. For unpublished trials, available information from conference proceedings will be screened.
Assessment of trial quality
A quality score will be applied to describe the adequacy of allocation concealment: A. low risk of bias in the randomization process (eg randomization by telephone call to central office). B. moderate risk of bias (eg sealed envelopes) C. high risk of bias D. trials where there was insufficient information to score allocation concealment
Data extraction
Initial data will be extracted independently by CM and NW. This will include baseline characteristics of the patients, the interventions being tested, tumour response rates, median survivals, and information about toxicity and quality of life. Hazard ratios and confidence intervals will be derived by extracting and combining study estimates according to the method described in Parmar 1998.
Analysis
Results of eligible studies will be statistically synthesised (meta-analysis) if appropriate. It is inevitable that some post hoc judgment will be required, because a number of different questions may be posed, and there may only be one or two trials addressing particular questions. Tumour response rates as reported will be analysed as categorical variables and a pooled relative risk derived if appropriate. It is unlikely that anything other than a narrative review of toxicity and quality of life data will be possible.
