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Clinicians' adherence versus non adherence to practice guidelines in the management of patients with sarcoma: a cost-effectiveness assessment in two European regions

  • Lionel Perrier1Email author,
  • Alessandra Buja2,
  • Giuseppe Mastrangelo3,
  • Antonella Vecchiato4,
  • Paolo Sandonà5,
  • Françoise Ducimetière6,
  • Jean-Yves Blay7,
  • François Noël Gilly8,
  • Carole Siani9,
  • Pierre Biron10,
  • Dominique Ranchère-Vince11,
  • Anne-Valérie Decouvelaere12,
  • Philippe Thiesse13,
  • Christophe Bergeron14,
  • Angelo Paolo Dei Tos15,
  • Jean-Michel Coindre16,
  • Carlo Riccardo Rossi17 and
  • Isabelle Ray-Coquard18
BMC Health Services Research201212:82

DOI: 10.1186/1472-6963-12-82

Received: 28 July 2011

Accepted: 28 March 2012

Published: 28 March 2012

Abstract

Background

Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not.

Methods

Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhône-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros (€) at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method.

Results

A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%.

Conclusions

Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma.

Keywords

Sarcoma Cancer Clinical practice guidelines Adherence Compliance Cost-effectiveness

Background

Sarcomas are rare tumours (accounting for only 1-2% of all cancers) originating from connective tissue, skin, retroperitoneum, bone and viscera [1]. The rarity of the disease, along with the variety of histological types and locations and the heterogeneity of prognostic factors associated with local or distant spread, mean that physicians have only limited personal experience of managing the disease. Furthermore, outside centres of excellence, there is little graduate or post-graduate medical training in its optimum management. To improve the diagnosis and prognosis of sarcoma, the European Commission funded the Connective Tissue Cancer Network (CONTICANET) aimed at increasing the standardization of diagnostic and therapeutic procedures.

In order to reduce inappropriate medical procedures, Clinical Practice Guidelines (CPGs) were developed by the Fédération Nationale des Centres de Lutte contre le Cancer (the French Federation of Comprehensive Cancer Centres) [2] and by the Italian National Research Council [3]. France and Italy reached a consensus in their CPGs relating to all phases of sarcoma management (initial examination and diagnosis, histopathological report, surgery, chemotherapy, and radiation therapy) except surveillance after therapy (see Annexe 1).

The impact of adherence to CPGs has received some research attention [410], even in the management of rare cancers [1114]. However, little is known about the financial impact of clinicians' adherence to CPGs in general, and the impact of adherence on outcomes and costs of care has only rarely been simultaneously considered [15]. Such assessments are of particular value in the current period of budgetary constraint, which prevents the achievement of improved cancer outcomes through increased health expenditure [16, 17].

We therefore assessed the cost-effectiveness of compliance with CPGs in sarcoma management by investigating the relationship between health outcome and resource consumption in patients treated in the regions of the Rhône-Alpes in France and Veneto in Italy.

Methods

Study design

Our starting point was 327 sarcoma patients aged ≥ 15 years (254 in Veneto and 73 in Rhône-Alpes) diagnosed over the relevant periods in the two regions. Absence of patient consent, care undertaken outside the participating regions or in private hospitals, and missing records (Table 1) reduced the number of patients included in the study to 219, 58 from Rhône-Alpes and 161 from Veneto. These patients were followed retrospectively for the three years after sarcoma diagnosis or until the date of death. All patients had histological confirmation of primary malignant sarcoma, with or without distant metastasis at initial diagnosis. With the exception of osteosarcoma, sarcomatoid carcinoma, mesothelioma, neuroblastoma, paraganglioma and mixed (epithelial and mesenchymal) tumours of the female genital tract, all histological subtypes were included. All patients in Rhône-Alpes had been diagnosed between March 2005 and February 2006 and treated at the University Hospital of Lyon and/or at the Léon Bérard Cancer Centre. All patients in Veneto had been diagnosed between January 2007 and December 2007 and treated in the public hospitals of the region. Patients were managed in accordance with the ethical principles for medical research involving human subjects described in the Declaration of Helsinki. The study received approval in France from the National Ethics Committee (N°904073) and the National Committee for Protection of Personal Data (N°05-1102), and from the Local Sanitary Agency of the Veneto Region and the Ethics Committee of the Azienda Ospedaliera di Padova (N°156/06/CE) in Italy. Each patient was required to give signed informed consent. Lack of informed consent and treatment of sarcoma outside the Veneto or Rhône-Alpes were exclusion criteria. Cases of relapsed disease were also excluded since CPGs for this setting are not available.
Table 1

Attrition of the study population

Region

Eligible

No consent

Care outside the region

Data not available@

Included

Veneto

254

55

17

21

161

Rhône-Alpes

73

0

6

9

58

Total

327

55

23

30

219

@patients treated at private hospitals; missing clinical records

Clinical data

Hospital records were used to obtain data on the characteristics of patients (age, sex, comorbidities) and their sarcomas (visceral or soft tissue; superficial or deep tumour); localization in lower or upper limb, head-neck or trunk; histological subtype; major tumour diameter at imaging and surgery; and grade). Data were also obtained on resources utilization (using a micro-costing approach) at diagnosis and during surgery (primary and wide surgical resection), chemotherapy (drugs administered in hospital or outpatient facilities) and radiotherapy (sessions in hospital or outpatient facilities). We also obtained data covering relapse or metastasis during follow up, along with any subsequent need for surgical interventions, chemotherapy and/or radiotherapy. Information was collected on number of days of hospitalization, use of pathology resources such as micro-biopsy and cytology), use of imaging, and supportive treatments such as antibiotics. The date of relapse was used to calculate relapse free survival from diagnosis.

Physicians independent of the study (two from the Léon Bérard Cancer Centre and two from the University of Padua) assessed whether or not there had been compliance with CPGs in each management phase covered by such guidelines. Overall management was considered to have been compliant only when CPGs had been followed at all stages of diagnosis, treatment, and follow-up.

Costs and indicators of effectiveness

Costs were assessed for each patient and from the hospital's point of view for the period between diagnosis and the end of follow-up or death [18]. Sources of unit costs and prices are described in Table 2[1921]. Days of hospital admission were multiplied by the cost per day (taking the average of the 2009 costs in France and Italy). This covered the cost of personnel, medications (except for chemotherapy and blood transfusions), use of medical devices, laboratory tests, depreciation of equipment and overheads. Doses of chemotherapy, and number of transfusions, radiotherapy sessions, imaging procedures, biopsies and consultations were multiplied by their respective unit costs (again taking the average of 2009 prices in France and Italy). Discounting of 4% per year was applied. The mean costs were calculated for patients whose overall management had been compliant with CPGs and for patients in whom it had not.
Table 2

Main unit costs and prices

Items

Unit costs and prices

Sources of information

Hospitalization (per day)

760,14€

Hospital Managers

Biopsy

51,45 €

[19, 20]

Consultation (external)

68,73€

[19, 20]

Radiotherapy (per session)

94,21€

[19, 20]

Chemo-therapy(per milligram of drugs)

Caelix

17,74€

Hospital pharmacists

 

Carboplatin

0,21€

Hospital pharmacists

 

Cisplatin

0,32€

Hospital pharmacists

 

Deticene

0,03€

Hospital pharmacists

 

Doxorubicin

0,71€

Hospital pharmacists

 

Etopophos etoposide

0,16€

Hospital pharmacists

 

Gemcitabine

0,17€

Hospital pharmacists

 

Holoxan

0,07€

Hospital pharmacists

 

Ifosfamide

0,10€

Hospital pharmacists

 

Imatinib

0,24€

Hospital pharmacists

 

Melphalan

0,01€

Hospital pharmacists

 

Navelbine

1,91€

Hospital pharmacists

 

Oxaliplatin

3,92€

Hospital pharmacists

 

Paclitaxel

2,25€

Hospital pharmacists

 

Vincristine

7,16€

Hospital pharmacists

Transfusion (per pack)

Ps

121,33€

[19, 21]

 

Red blood cell

104,57€

[19, 21]

Imaging(per exam.)

Chest radiograph

22,49€

[19, 20]

 

Colonoscopy

121,58€

[19, 20]

 

Computed Tomography

83,20€

[19, 20]

 

Ultrasound

50,48€

[19, 20]

 

Magnetic Resonance Imaging

139,50€

[19, 20]

Relapse-free survival three years after diagnosis was taken as the indicator of effectiveness. Mean relapse-free survival was calculated for CPG-compliant and non compliant groups.

Statistical analysis

Chi-square or t-tests were used, according to the type of data, to compare compliant (CPG+) and non compliant (CPG-) groups. Analysis of variance (ANOVA) was used to explore the costs of overall management according to histological subtype. Univariate survival analyses were performed using the Kaplan-Meier method and the log-rank test. The log-rank test was used to assess the effect of compliance with CPGs on survival after adjusting for confounding variables.

The incremental cost-effectiveness ratio (ICER), expressing the incremental cost per additional relapse-free year gained.

The uncertainty surrounding the ICER was captured by a probabilistic sensitivity analysis according to procedures established by the French National Authority for Health (HAS) [22]. Ten thousand replications were obtained by the non parametric bootstrap method. A graphical representation of the sampling uncertainty associated with the ICER on the cost-effectiveness plane is shown in Figure 1[23]. The four quadrants of the cost-effectiveness plane are as follows: northeast, compliance with CPGs more costly and more effective than non compliance; southeast, compliance less costly, more effective; northwest (more costly, less effective) and southwest (less costly, less effective). Confidence regions were assessed and are represented by ellipses.
https://static-content.springer.com/image/art%3A10.1186%2F1472-6963-12-82/MediaObjects/12913_2011_Article_2013_Fig1_HTML.jpg
Figure 1

Probabilistic analysis of the ICER: scatter of points and confidence ellipses.

The outer ellipse defines the confidence region for the mean cost difference and mean effect difference pair at the 95% level and the inner ellipse at the 50% level. The outer ellipse is equivalent to an acceptability region for an inference test at 5% significance level whose null hypothesis is the mean cost difference and mean effect difference pair being equal to (0, 0). Consequently, if the origin of the cost-effectiveness plane does not belong to the confidence ellipse, then both the management of patients with sarcoma (adherence versus non adherence to CPGs) are significantly different regarding costs and effects. For more robustness in the results, in addition to confidence ellipses, uncertainty around the ICER was taken into account by examining probabilities that it belonged to each of the quadrants of the cost-effectiveness plane.

Calculations were performed using STATA 11 and Gauss software version 9.0.

Results

Table 3 shows the key characteristics of patients and the health outcome in the whole of the study population (219 cases) and in the CPG + (n = 118) and CPG- (n = 101) groups. Overall, age at diagnosis, ranging from 18 to 94 years, was in average 60 years and the majority of patients studied (55%) were women. There was a variety of histological types, the most frequent being Gastro Intestinal Stromal Tumors(GIST) (26%), liposarcomas (21%) and leiomyosarcomas (12%). Sixtythree percent of tumors were of soft tissue, mostly in the trunk, and 81% deep seated. Tumors had a mean size of 95 mm (range 3 to 450 mm). Tumors were grade II/III in 58% of cases, Thirtytwo patients (15%) had previous cancers. Differences between CPG compliant and non compliant groups were significant for grade (there were more high grade tumors in patients whose management did not comply with CPGs, p = 0.01) and histological type (p = 0.03): CPGs was less likely in liposarcoma and leiomyosarcoma. Relapse free survival was a mean of 2.46 years in the CPG + group and 2.16 years in the non-compliant group (p = 0.04).
Table 3

Clinical characteristics of patients by group: Mean ± SD or number of patients and (%)

Clinical characteristics

All patients n = 219

CPG (+) n = 118

CPG (-) n = 101

p

Age (years)

60.4 ± 15.0

60.1 ± 15.3

60.7 ± 14.8

0.39

Sex (females)

121 (55.2%)

66 (56.0%)

55 (54.5%)

0.83

Previous cancer

32 (14.8%)

15 (12.8%)

17 (17.2%)

0.37

Tumour grade

low (grade I)

38 (20.3%)

27 (27.6%)

11 (12.4%)

0.01

 

intermediate (grade II)

38 (20.3%)

18 (18.3%)

20 (22.5%)

 
 

high (grade III)

70 (37.5%)

27 (27.6%)

43 (48.3%)

 
 

not applicable

41 (21.9%)

26 (26.5%)

15 (16.8%)

 

Tumour site

soft tissues

137 (62.6%)

71 (60.2%)

66 (65.4%)

0.43

 

viscera

82 (37.4%)

47 (39.8%)

35 (34.6%)

 

Tumour size in mm

94.6 ± 80.6

96.8 ± 91.4

91.9 ± 66.3

0.67

Tumour depth

superficial

38 (18.9%)

22 (20.6%)

16 (17%)

0.52

depth

deep

163 (81.1%)

85 (79.4%)

78 (83%)

 

Histology

GIST

54 (25.6%)

37 (32.5%)

17 (17.5%)

0.03

 

Liposarcoma

45 (21.3%)

18 (15.8%)

27 (27.8%)

 
 

Leiomyosarcoma

25 (11.8%)

9 (7.9%)

16 (16.5%)

 
 

Sarcoma NOS

16 (7.6%)

9 (7.9%)

7 (7.2%)

 
 

Dermatofibrosarcoma

16 (7.6%)

11 (9.6%)

5 (5.2%)

 
 

Others

55 (26.1%)

30 (26.3%)

25 (25.8%)

 

Relapse free survival (years)

2.40

2.46

2.16

0.04

NOS: Not Otherwise Specified

GIST: Gastro Intestinal Stromal Tumours

Table 4 shows details of the mean costs in CPG + and CPG- groups. The overall (for all 219 cases) cost of sarcoma management per patient, ranging from €1,303 to €107,464, reached €25,296 in average. Surgery (primary and wide surgical excisions), with an average cost of €8,170 represented 32% of the average total cost. Chemotherapy (€6,107) accounted for 24% of the average total cost, follow up (€5,048) for 20% of the average total cost and diagnosis (€3,701) for 15%. Radiotherapy (€2,270) represented 9% of the average total cost. Overall average cost per patient of managing sarcomas (all subtypes included) was somewhat less in the GPG + group than in the CPG- group, but the difference did not reach statistical significance (p = 0.07). Overall average cost was significantly lower in the GPG + group than in the CPG- group for GIST and dermatofibrosarcoma (p < 0.01).
Table 4

Average costs for each phase of sarcoma management by group (in €, 2009)

Phases of treatment

All patients

CPG (+)

CPG (-)

p

Diagnosis

overall

3,701 (7420)

4,536 (8,908)

2,728 (5,095)

0.07

 

hospitalization

3,275 (7,376)

4,097 (8,791)

2,317 (4,701)

0.07

 

imaging

259 (198)

274 (210)

241 (182)

0.21

 

biopsy

93 (57)

88 (45)

99 (69)

0.15

 

consultation

74 (96)

77 (88)

71 (105)

0.64

Surgery

overall

8,170 (7,364)

7,397 (6,034)

9,075 (8,639)

0.09

 

hospitalization

7,927 (7,101)

7,163 (5,773)

8,821 (8,363)

0.09

 

imaging

95 (163)

108 (179)

80 (141)

0.21

 

transfusion

148 (384)

126 (384)

174 (386)

0.36

Chemo-therapy

overall

6,107 (11,988)

5,164 (11,197)

7,207 (13,123)

0.22

 

hospitalization

3,913 (8,568)

2,938 (7,176)

5,050 (9,905)

0.07

 

consultation

59 (405)

81 (545)

35 (98)

0.39

 

transfusion

56 (223)

53 (228)

60 (220)

0.20

 

drugs

1,956 (5,171)

1,982 (5,964)

1,925 (4,115)

0.94

 

imaging

123 (279)

110 (277)

137 (284)

0.48

Radio-therapy

overall

2,270 (5,850)

2,078 (5,599)

2,493 (6,173)

0.60

 

hospitalization

1,544 (5,223)

1,449 (4,867)

1,656 (5,658)

0.77

 

sessions

726 (1,266)

629 (1,269)

837 (1,262)

0.23

Initial treatment

20,248 (18,474)

19,175 (17,555)

21,502 (19,778)

0.36

Follow Up

5,048 (11,760)

4,396 (12,343)

5,811 (11,116)

0.38

Overall management

25,296 (22,919)

23,571 (21,913)

27,313 (24,403)

0.23

Table 5 shows that compliance with CPGs was less costly and more effective than non compliance. On the basis of the ICER point estimate, clinicians' adherence to CPGs in the management of patients with sarcoma strictly dominates non adherence for relapse free survival. Since the origin of the cost-effectiveness plane presented in Figure 1 was not included in the inner 95% confidence ellipse, clinicians' adherence versus non adherence to CPGs is significantly different in terms of cost and effectiveness. The probability of the ICER belonging to each quadrant of the cost-effectiveness plane is highest (75%) for the southeast quadrant, in which compliance with CPG is both less costly and more effective than non compliance. This is in accordance with the results of Table 5 also concluding for less costly and more effectiveness in compliant group.
Table 5

Incremental cost-effectiveness ratio (ICER) for clinicians' adherence versus non adherence to clinical practice guidelines (CPGs)

 

Mean cost per patient(€, 2009)

Mean Incremental Cost[[]](€, 2009)

Mean effectiveness per patient(Relapse-free survival, years)

Mean Incremental Effectiveness[[]](Relapse-free survival, years)

ICER(€ per relapse-free year gained)[[]]

Overall management CPG (+)

23,571

-

2.46

-

 

Overall management CPG (-)

27,313

3,742

2.16

-0.30

Dominated

Discussion

A weakness of the present study is that its retrospective nature did not allow assessment of outcome in cost per Quality Adjusted Life Year (QALY), as recommended by the National Institute for Health and Clinical Excellence (NICE) [24, 25]. Notwithstanding this, freedom from relapse undoubtedly contributes to quality of life in cancer patients.

Another weakness was the lack of information on potentially confounding variables such as the initial performance status of the patient, the cumulative volume for the surgeon and the hospital, the type of provider (academic cancer centre, non academic cancer centre, non academic non cancer centre) [2628] that could not be controlled for in the statistical analysis. Any resulting bias, however, would have tended to cause an underestimation rather than an overestimation of the true effect of compliance, since in the CPG + group the costs of diagnosis were higher (Table 4) despite a lower grade of tumours (Table 3).

Interestingly, the higher overall cost involved in diagnosing patients according to CPGs was accounted for almost entirely by increased hospitalisation (rather than by greater use of imaging or biopsy or external consultations) (Table 4). The average cost of hospitalization was €4,097 in CPG + and €2,317 in CPG- groups. The difference corresponds to 2.3 additional days of hospital stay at the prevailing daily cost of €760 per day (Table 2). Adherence to CPGs requires that decisions be made within a multidisciplinary committee, and it is likely that patients' hospitalization was prolonged in order to schedule the multidisciplinary meeting needed to reach a consensus on treatment.

A greater adherence to CPGs during diagnosis appears to decrease all subsequent costs, notably those of surgery and chemotherapy, probably by reducing the need for surgical re-intervention or more intense use of antineoplastic drugs (Table 4). Surgery and chemotherapy were the main factors driving the cost of initial treatment, representing about 66% of the overall cost in the CPG + group ((7,397 + 5,164)/19,175) and 76% ((9,075 + 7,207)/21,502) in the CPG- group.

In contrast to other studies that have shown it may be cheaper in the short term to deviate from CPGs [29], the present study found that compliance with CPGs strictly dominates for relapse-free survival, meaning that management of sarcoma according to CPGs is less costly and more effective. This evidence should encourage health providers to promote adherence to guidelines since adopting this approach achieves a better quality of care and is a more efficient allocation of resources. It should also encourage compliance among physicians, some of whom perceive CPGs as limiting their freedom to make diagnostic and therapeutic decisions.

Compliance with CPGs in sarcoma management has increased since 2001. A retrospective study of the medical records of sarcoma patients in the University Hospital of Lyon and the Cancer Centre Léon Bérard found that between 1999 and 2001 initial clinical management had been consistent with the CPG in only 32% of cases [12]. In this study, the compliance rate reached 54%. Compliance with guidelines was greater for chemotherapy than for other aspects of sarcoma management since detailed protocols are more common than in diagnosis, surgery, radiotherapy or follow up. Compliance with CPGs was also more frequent for low-grade than for high-grade sarcomas (p = 0.01); and it has been suggested that physicians are less likely to adhere to CPGs if they believe that compliance will not improve outcome [30]. Compliance was also better for GIST than for other histologies, probably because imatinib and related drugs have led to a remarkable improvement in management on which there is global consensus [31].

Conclusions

The present findings should encourage physicians' efforts to increase their compliance with CPGs and encourage healthcare administrators to invest in implementing CPGs in the management of sarcoma.

Abbreviations

ANOVA: 

Analysis of variance

CEA: 

Cost-effectiveness analysis

CPG: 

Clinical practice guidelines

CPG +: 

Clinicians' adherent to practice guidelines

CPG-: 

Clinicians' non adherent to practice guidelines

CONTICANET: 

Connective tissues cancers network

GIST: 

Gastro Intestinal Stromal Tumours

HAS: 

French National Authority for Health (Haute Autorité de Santé)

ICER: 

Incremental cost-effectiveness ratio

NICE: 

National Institute for Health and Clinical Excellence

NOS: 

Not otherwise specified

QALY: 

Quality adjusted life year

Declarations

Acknowledgements

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement n°278742, the Network of Excellence CONTICANET (contract code: FP-018806), Canceropole Lyon Auvergne Rhone-Alpes CLARA (contract code: 2010 ProCan IV-2ERPCS), and Merck Serono. The authors thank for their collaboration Eurosarc, CONTICANET, CLARA and Merck Serono for financial support, as well as Giuseppe Zamengo (Direzione Regionale Risorse Socio Sanitarie, Servizio Sistema Informativo Socio Sanitario e Tecnologie Informatiche, Regione Veneto), Pr Cyrille Colin (Direction de l'information hospitalière, Hospices Civils de Lyon), Dr Frédéric Gomez (Direction de l'information hospitalière, Centre Léon Bérard), Mr Nicolas Caquot (Direction administrative et financière, Centre Léon Bérard), and Mrs Marine Genton (Master student, Université Lumière Lyon 2). The authors would like to thank the referees for their insightful comments and suggestions. Rob Stepney, medical writer, Charlbury, UK, assisted with the final editing of the manuscript.

Appendix A. Annexe 1. Main CPG criteria for each sequence of initial sarcoma treatment

Main Criteria for diagnosis: Clinical size and depth of the tumour mass must be recorded; Computed Tomography (CT) is required for abdominal localizations, or Magnetic Resonance Imaging (MRI) for limb localizations; Chest radiograph or CT scan is required to identify metastases; Initial biopsy (incisional or needle), preferably by the surgeon in charge of future surgical procedures, is required for bone and soft tissue sarcomas, with the exception of small tumours (< 3 cm) for which excisional biopsy is considered appropriate.

Main Criteria for surgery: Whenever possible, primary surgery should involve a wide excision with 1-2 cm margins. For high-grade, large (> 3 cm) or deep-seated tumours, surgery alone is acceptable only in case of amputation or compartmental resection with negative histological margins (R0). Wide excision alone, with no adjuvant treatment, is acceptable only for superficial, small (< 3 cm) and low-grade lesions. Histologically positive margins (R1) or incomplete excision (R2) have to be considered inadequate, and should be followed by further appropriate treatment.

Main criteria for chemotherapy: For non-readily operable sarcomas, primary chemotherapy or radiation therapy can be an option. For readily operable sarcomas, neo-adjuvant chemotherapy should be performed only as part of a clinical research protocol. In the adjuvant setting, systemic chemotherapy should be performed only within the context of a prospective clinical trial. Adjuvant chemotherapy can be performed for patients with histologically positive margins after wide surgical excision.

Main criteria for radiation therapy: Association of wide surgical excision and adjuvant radiation therapy should be considered the standard treatment. The absence of adjuvant radiotherapy is acceptable for superficial, small (< 3 cm) and low-grade tumours, and for limb sarcomas when amputation is performed. For non-operable sarcomas, primary radiation therapy could be an option. The optimal treatment strategy involves a 50 Gy delivered dose with an additional boost of 10 Gy in case of microscopic residual tumour (R1), with a target volume encompassing the tumour bed and surgical scars, including draining orifices, with adapted security margins. Moreover, the interval from surgery to radiation therapy must not be longer than 8 weeks.

Authors’ Affiliations

(1)
Department Cancer and Environment, Cancer Centre Léon Bérard, University of Lyon, F-69007 Lyon; CNRS, GATE Lyon-St Etienne, UMR n°5824, 69130 Ecully
(2)
Department of Environmental Medicine and Public Health, University of Padova
(3)
Department of Environmental Medicine and Public Health, Padua University
(4)
Melanoma and Sarcomas Unit, Veneto Institute of Oncology, IOV, IRCCS
(5)
Department of Environmental Medicine and Public Health, Padua University
(6)
University of Lyon, Cancer Centre Léon Bérard; Santé-Individu-Société EA-INSERM 4129
(7)
Department of Medical Oncology, Cancer Centre Léon Bérard, University of Lyon
(8)
Department of Digestive Surgery, University Hospital Lyon Sud
(9)
ERIC EA 3083, University of Lyon (University Claude Bernard Lyon 1)
(10)
Department of Medical Oncology, University of Lyon, Cancer Centre Léon Bérard
(11)
Department of Anatomopathology, Centre Léon Bérard
(12)
Department of Anatomopathology, Centre Léon Bérard
(13)
Department of Imaging, Centre Léon Bérard
(14)
Institut d'Hémato-Oncologie Pédiatrique
(15)
Department of Pathology, Hospital of Treviso
(16)
Department of Pathology, Institut Bergonie
(17)
Melanoma and Sarcomas Unit, Veneto Institute of Oncology, IOV, IRCCS, University of Padova
(18)
Centre Léon Bérard, Department of Medical Oncology, University de Lyon, INSERM EA 4129 « SIS »

References

  1. Mastrangelo G, Fadda E, Cegolon L, Montesco MC, Ray-Coquard I, Buja A, Fedeli U, Frasson A, Spolaore P, Rossi CR: A European project on incidence, treatment, and outcome of sarcoma. BMC Publ Health. 2010, 10: 188-10.1186/1471-2458-10-188.View ArticleGoogle Scholar
  2. FNCLCC: Standards, Options et Recommandations pour la prise en charge des patients adultes atteints de sarcome des tissus mous, de sarcome utérin ou de tumeur stromale gastro-intestinale. 1995, [http://www.sor-cancer.fr/]Google Scholar
  3. Italian National Research Council in Italy. [http://progettooncologia.cnr.it/bridge/attivita-direzione.html]
  4. Mercuri M, Gafni A: Medical practice variations: what the literature tells us (or does not) about what are warranted and unwarranted variations. J Eval Clin Pract. 2011, 17: 671-677. 10.1111/j.1365-2753.2011.01689.x.View ArticlePubMedGoogle Scholar
  5. Ray-Coquard I, Philip T, Ray-Coquard I, Philip T, De LG, Froger X, Suchaud JP, Voloch A, Mathieu-Daudé H, Fervers B, Farsi F, Browman GP, Chauvin F: A controlled "before-after" study: impact of a clinical guidelines programme and regional cancer network organization on medical practice. Br J Cancer. 2002, 86: 313-321. 10.1038/sj.bjc.6600057.View ArticlePubMedPubMed CentralGoogle Scholar
  6. Ray-Coquard I, Philip T, De LG, Froger X, Suchaud JP, Voloch A, Mathieu-Daudé H, Lurkin A, Farsi F, Bertrand P, Chauvin F: Persistence of medical change at implementation of clinical guidelines on medical practice: a controlled study in a cancer network. J Clin Oncol. 2005, 23: 4414-4423. 10.1200/JCO.2005.01.040.View ArticlePubMedGoogle Scholar
  7. Kaegi L: Policy, management, and clinical practice implications get priority attention of health services researchers. QRB Qual Rev Bull. 1991, 17: 297-304.PubMedGoogle Scholar
  8. Audet AM, Greenfield S, Field M: Medical practice guidelines: current activities and future directions. Ann Intern Med. 1990, 113: 709-714.View ArticlePubMedGoogle Scholar
  9. Ray-Coquard I, Philip T, Lehmann M, Fervers B, Farsi F, Chauvin F: Impact of a clinical guidelines program for breast and colon cancer in a French cancer center. JAMA. 1997, 278: 1591-1595. 10.1001/jama.1997.03550190055044.View ArticlePubMedGoogle Scholar
  10. Osarogiagbon RU, Phelps G, McFarlane J, Bankole O: Causes and consequences of deviation from multidisciplinary care in thoracic oncology. J Thorac Oncol. 2011, 6: 510-516. 10.1097/JTO.0b013e31820b88a7.View ArticlePubMedGoogle Scholar
  11. Grimer R, Judson I, Peake D, Seddon B: Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010, 201: 506182.Google Scholar
  12. Ray-Coquard I, Thiesse P, Ranchere-Vince D, Chauvin F, Bobin JY, Sunyach MP, Carret JP, Mongodin B, Marec-Bérard P, Philip T, Blay JY: Conformity to clinical practice guidelines, multidisciplinary management and outcome of treatment for soft tissue sarcomas. Ann Oncol. 2004, 15: 307-315. 10.1093/annonc/mdh058.View ArticlePubMedGoogle Scholar
  13. Jansen-Landheer ML, Krijnen P, Oostindiër MJ, Kloosterman-Boele WM, Noordijk EM, Nooij MA, Steup WH, Taminiau AH, Vree R, Hogendoorn PC, Tollenaar RA, Gelderblom H: Improved diagnosis and treatment of soft tissue sarcoma patients after implementation of national guidelines: a population-based study. Eur J Surg Oncol. 2009, 35: 1326-1332. 10.1016/j.ejso.2009.05.002.View ArticlePubMedGoogle Scholar
  14. Cutts S, Andrea F, Piana R, Haywood R: The management of soft tissue sarcomas. Surgeon. 2012, 10: 25-32. 10.1016/j.surge.2011.09.006.View ArticlePubMedGoogle Scholar
  15. Fritz JM, Cleland JA, Brennan GP: Does adherence to the guideline recommendation for active treatments improve the quality of care for patients with acute low back pain delivered by physical therapists?. Med Care. 2007, 45: 973-980. 10.1097/MLR.0b013e318070c6cd.View ArticlePubMedGoogle Scholar
  16. Lichtenberg F: The expanding pharmaceutical arsenal in the war on cancer. NBER. 2004, Working Paper n°10328Google Scholar
  17. Martin S, Rice N, Smith PC: Does health care spending improve health outcomes? Evidence from English programme budgeting data. J Health Econ. 2008, 27: 826-842. 10.1016/j.jhealeco.2007.12.002.View ArticlePubMedGoogle Scholar
  18. Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL: Methods for the economics evaluation of health care programme. 2005, New-York: Oxford University Press, 3Google Scholar
  19. Regione del Veneto, Nomenclatore Tariffario Prestazioni Specialistiche Ambulatoriali. [http://www.regione.veneto.it/NR/rdonlyres/180C6757-EB04-4AB2-8404-681093D15379/0/ALLEGATO_1_vigenti_delibera.pdf]
  20. Classification commune des actes médicaux.[http://www.ameli.fr/accueil-de-la-ccam/trouver-un-acte/consultation-par-chapitre.php?add=16.2.5]
  21. Arrêté du 2 janvier 2008 relatif au tarif de cession des produits sanguins labiles. Journal officiel de la République française. 10 février 2008, N°35 [http://www.journal-officiel.gouv.fr/frameset.html]
  22. Haute autorité de santé (HAS): Choix méthodologiques pour l'évaluation économique à la HAS. [http://www.has-sante.fr/portail/upload/docs/application/pdf/2011-11/guide_methodo_vf.pdf]
  23. Claxton K, Sculpher M, McCabe C, Briggs A, Akehurst R, Buxton M, Brazier J, O'Hagan T: Probabilistic sensitivity analysis for NICE technology assessment: not an optional extra. Health Econ. 2005, 14: 339-347. 10.1002/hec.985.View ArticlePubMedGoogle Scholar
  24. McCabe C, Claxton K, Culyer AJ: The NICE cost-effectiveness threshold: what it is and what that means. PharmacoEconomics. 2008, 26: 733-744. 10.2165/00019053-200826090-00004.View ArticlePubMedGoogle Scholar
  25. National Institute for Health and Clinical Excellence. [http://www.nice.org.uk/media/68D/29/The_guidelines_manual_2009_-_Chapter_7_Assessing_cost_effectiveness.pdf]
  26. Salloum RG, Smith TJ, Jensen GA, Lafata JE: Factors associated with adherence to chemotherapy guidelines in patients with non-small cell lung cancer. Lung Cancer. 2011Google Scholar
  27. Chamie K, Saigal CS, Lai J, Hanley JM, Setodji CM, Konety BR: Litwin MS; Urologic Diseases in America Project: Compliance with guidelines for patients with bladder cancer: Variation in the delivery of care. Cancer. 2011, 117: 5392-5401. 10.1002/cncr.26198.View ArticlePubMedPubMed CentralGoogle Scholar
  28. Lebeau M, Mathoulin-Pélissier S, Bellera C, Tunon-de-Lara C, Daban A, Lipinski F, Jaubert D, Ingrand P: Migeot V; REPERES Group: Breast cancer care compared with clinical Guidelines: an observational study in France. BMC Publ Health. 2011, 11: 45-10.1186/1471-2458-11-45.View ArticleGoogle Scholar
  29. Ozminkowski RJ, Wang S, Marder WD, Azzolini J: Short-run associations between medical care expenditures and adherence to clinical practice guideline-based measures for diabetes. Value Health. 2000, 3 (Suppl 1): 29-38.View ArticlePubMedGoogle Scholar
  30. Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, Rubin HR: Why don't physicians follow clinical practice guidelines? A framework for improvement. JAMA. 1999, 282: 1458-1465. 10.1001/jama.282.15.1458.View ArticlePubMedGoogle Scholar
  31. Reichardt P, Blay JY, Mehren M: Towards global consensus in the treatment of gastrointestinal stromal tumor. Expert Rev Anticancer Ther. 2010, 10: 221-232. 10.1586/era.09.171.View ArticlePubMedPubMed CentralGoogle Scholar
  32. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/82/prepub

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