Questions about the importance of radiation therapy in the treatment of soft tissue sarcoma (A; 320 respondents) and the utilization of radiation therapy in the treatment of soft tissue sarcoma (B; 317 respondents), stratified by physician specialty. Questions were scored on a 5-point Likert scale. For each question, mean values were calculated to generate a single response score (a range from 1 indicating not essential to 5 indicating essential). Error bars indicate SEM.
Questions about the importance of chemotherapy in the treatment of soft tissue sarcoma (A; 320 respondents) and the utilization of chemotherapy in the treatment of soft tissue sarcoma (B; 315 respondents), stratified by physician specialty. Questions were scored on a 5-point Likert scale. For each question, mean values were calculated to generate a single response score (a range from 1 indicating not essential to 5 indicating essential). Error bars indicate SEM.
Wasif N, Smith CA, Tamurian RM, Christensen SD, Monjazeb AM, Martinez SR, Canter RJ. Influence of Physician Specialty on Treatment Recommendations in the Multidisciplinary Management of Soft Tissue Sarcoma of the Extremities. JAMA Surg. 2013;148(7):632-639. doi:10.1001/jamasurg.2013.113
Although prospective randomized data are available to guide the multidisciplinary management of soft tissue sarcoma (STS) of the extremities, controversy exists regarding adjuvant chemotherapy and radiation therapy.
To determine if clinical specialty introduces bias in recommendations for multimodality treatment of STS.
Database of active members of the American Society of Clinical Oncology, the Society of Surgical Oncology, and the Connective Tissue Oncology Society.
Members of specialty oncology societies with an active interest in STS.
Main Outcomes and Measures
Survey responses regarding the multidisciplinary management of STS were scored on a 5-point Likert scale and analyzed using analysis of variance.
The questionnaire was completed by 320 of 490 potential respondents (65%), including medical (18%), radiation (8%), orthopedic (22%), and surgical oncologists (45%). Respondents concurred on the use of radiation therapy for margins positive for tumor, for high-grade tumors, for improvement in local control, for tumors larger than 10 cm, and for tumors in close proximity to a neurovascular bundle. Respondents diverged on the use of radiation therapy for tumors 5 to 10 cm in size, for low-grade tumors, for radiation-associated STS, and for survival benefit. Only radiation oncologists felt that radiation therapy was underutilized as a treatment modality (mean [SEM] Likert scale score, 2.44 [0.12]; P < .001). There was agreement on the use of chemotherapy for synovial sarcoma, for high-grade tumors, for tumors larger than 10 cm, for patients younger than 50 years of age, and for survival benefit. Medical oncologists were more likely to recommend chemotherapy for margins positive for tumor (mean [SEM] score, 3.12 [0.12]; P = .03) and for improvement in local control (mean [SEM] score, 2.91 [0.12] P = .08). Surgical oncologists placed the least emphasis on chemotherapy in the overall treatment plan (mean [SEM] score, 2.60 [0.07]; P = .001).
Conclusions and Relevance
Specialty bias exists in adjuvant treatment recommendations for STS. This highlights the importance of multidisciplinary STS tumor boards and interdisciplinary care to facilitate consensus decision making for individual patients.
The contemporary management of soft tissue sarcoma (STS) of the extremities requires coordinated multimodality treatment strategies involving several specialties in a multidisciplinary setting. For localized disease, surgical resection is the cornerstone of curative-intent therapy and, with the addition of radiation therapy, has been crucial in establishing limb-sparing surgery as the standard of care. This approach was validated in seminal randomized trials demonstrating equivalent survival outcomes between amputation and conservative limb-sparing surgery combined with radiation therapy.1,2
Although the magnitude of the benefit of adjuvant systemic chemotherapy for localized STS is modest, statistically significant improvements in disease-free and overall survival have been shown in some randomized phase III trials.3,4 The Sarcoma Meta-analysis Collaboration5 demonstrated an improvement in overall recurrence-free survival and a trend toward improved overall survival from pooled data. These findings were most notable for patients with STS of the extremities. Moreover, a more recent meta-analysis6 demonstrated improvement in overall survival when doxorubicin hydrochloride was used in combination with ifosfamide.
Despite the availability of data from randomized trials, variation in the multimodality treatment of patients with STS of the extremities exists. Although patient-specific factors have been identified that contribute to the variation in treatment and outcome, physician-specific factors have not been well studied. Martinez et al7 showed that African American patients with STS of the extremities receive lower rates of adjuvant radiation therapy and experience worse disease-specific survival than do white patients. Similarly, low socioeconomic status is associated with poorer overall survival for patients with STS.8 Recently, our group showed that physician experience influences treatment sequencing in STS.9
The objective for our study was to assess the influence of physician specialty in the management of patients with STS of the extremities. We hypothesized that clinical specialty leads to bias in recommendations for adjuvant radiation therapy and systemic chemotherapy among patients undergoing curative-intent surgery for STS of the extremities. As secondary objectives, we sought to explore patient- and tumor-specific factors influencing physician recommendations for radiation therapy and chemotherapy, as well as the specialty-specific perceived benefits of these treatments.
We conducted our study using survey methods. The survey was developed by 2 of the authors (N.W. and R.J.C.) following a literature review and a small focus group discussion. Pilot testing of the survey was performed internally at the University of California at Davis Medical Center in Sacramento for face and content validity to develop the final construct of 16 questions. Commercially available software (QuestionPro) was used for digitization and electronic dissemination via the World Wide Web in November 2009, as has been discussed previously.10 A cover paragraph explaining the purpose of our study accompanied the survey, and a reminder was sent to participants who did not respond to the initial request. No incentive was provided to complete the survey.
The complete survey questionnaire is provided in Table 1. The initial set of questions was structured to identify physician specialty. Subsequent modules addressed utilization of radiation therapy or systemic chemotherapy in the management of localized STS amenable to treatment with curative intent. Patient- and tumor-specific factors influencing the use of either radiation therapy or chemotherapy were queried. We did not specifically inquire about brachytherapy or intraoperative radiation therapy because these techniques are not widely available, even among academic, tertiary referral centers.
A pool of potential respondents was identified from the database of active members of the American Society of Clinical Oncology, the Society of Surgical Oncology, and the Connective Tissue Oncology Society. Only physicians with a self-declared subspecialty interest in STS were chosen. No unique information that could potentially identify a respondent was collected, and all data were deidentified. Approval for our study was obtained from the institutional review board at the University of California at Davis. Completion of the survey was considered as implied consent for participation.
Questions were scored on a 5-point Likert scale. For each question, mean values were calculated to generate a single response score. Mean values were compared using independent samples 1-way analysis of variance. The data were analyzed for homogeneity of variances, and the appropriate corrections were used for post hoc analysis. The significance level was set at P < .05 and adjusted as appropriate for multiple comparisons. For purposes of analyses, respondents were divided into groups by specialty. All tests were 2-tailed. Significance levels were set at P < .05, and confidence intervals at 95%. Statistical analysis was performed using SPSS version 16.0 statistical software (SPSS Inc).
The questionnaire was sent to 490 potential respondents and completed by 320 (65%). Data on the breakdown by specialty, by years in practice, and by percentage of clinical practice devoted to sarcoma care are outlined in Table 2. For specialty, “others” consisted primarily of pediatric hematologists/oncologists and pathologists.
Although respondents agreed that radiation therapy plays an important role in treatment overall (mean [SEM] Likert scale score, 3.81 [0.04]), significant variation in responses among specialties was observed. Radiation oncologists placed the most emphasis on the role of radiation therapy (mean [SEM] score, 4.26 [0.10]) (Figure 1A). Similarly, radiation oncologists were also more likely to think that radiation therapy was underutilized in the management of localized STS (mean [SEM] score, 2.44 [0.12]; P < .001) (Figure 1B).
The variables most likely to influence a treatment recommendation in favor of radiation therapy were the presence of margins positive for tumor (mean [SEM] Likert scale score, 4.50 [0.04]), the presence of a high-grade tumor (mean [SEM] score, 4.35 [0.04]), improvement in local control (mean [SEM] score, 4.29 [0.04]), the presence of a tumor larger than 10 cm (mean [SEM] score, 4.22 [0.05]), and the presence of a tumor close to a neurovascular bundle (mean [SEM] score, 4.07 [0.04]), ranked in order of importance (Table 3). Survival benefit was the least important consideration (mean [SEM] score, 2.67 [0.06]). A tumor size of 5 to 10 cm and patient age younger than 50 years ranked low as indications for adjuvant radiation therapy.
Interspecialty variation was observed in responses for all variables except for margins positive for tumor (Table 3). In particular, both radiation oncologists (mean [SEM] Likert scale score, 4.33 [0.14]) and medical oncologists (mean [SEM] score, 4.04 [0.08]) favored radiation therapy for tumors 5 to 10 cm in size compared with other specialists. For patients younger than 50 years of age, radiation oncologists were more likely to consider radiation therapy to be important (mean [SEM] score, 3.81 [0.18]) compared with surgical and medical oncologists. For tumors deep to the fascial plane, radiation oncologists were again more inclined to offer radiation therapy (mean [SEM] score, 4.46 [0.11]). Interestingly, radiation oncologists most strongly disagreed that radiation therapy was not indicated for low-grade tumors (mean [SEM] score, 2.13 [0.14]) or radiation-associated sarcoma (mean [SEM] score, 2.44 [0.22]). Of all respondents, radiation oncologists showed the highest agreement with an improvement in local control with adjuvant radiation therapy (mean [SEM] score, 4.63 [0.10]), whereas surgical oncologists showed the highest disagreement with a survival benefit from adjuvant radiation therapy (mean [SEM] score, 2.55 [0.09]).
We stratified respondents by years of practice (<5, 5-15, and >15 years) and percentage of clinical practice devoted to sarcoma care (<25%, 25%-75%, and >75%) to assess the effect of experience on factors influencing the use of radiation therapy. In all of the variables listed in Table 3, no significant difference in aggregate response was seen for respondents when considering percentage of clinical practice (<25%, 25%-75%, and >75%) independent of specialty. For years of practice, those respondents who had been in practice for 5 to 15 years were more likely to recommend radiation therapy for tumors larger than 10 cm than were those in practice for more than 15 years (mean [SEM] Likert scale score, 4.39 [0.06] vs 4.09 [0.08]; P = .011). A survival benefit for radiation therapy was more important for respondents in practice for more than 15 years than for those in practice for less than 5 years (mean [SEM] score, 2.86 [0.1] vs 2.35 [0.1]; P = .007).
Systemic chemotherapy was considered a less important factor than radiation therapy in the overall management strategy for STS of the extremities (mean [SEM] Likert scale score, 2.78 [0.05]). Again, variation in response by specialty was observed. Medical oncologists (mean [SEM] score, 3.00 [0.09]) placed the greatest emphasis on systemic chemotherapy, and surgical oncologists the least (mean [SEM] score, 2.60 [0.07]; P = .001) (Figure 2A). Overall, specialists agreed that systemic chemotherapy was appropriately utilized (mean [SEM] score, 3.17 [0.05]) (Figure 2B).
No single variable was rated as greater than 4.0 in the recommendation to utilize systemic chemotherapy. The presence of synovial sarcoma (mean [SEM] Likert scale score, 3.67 [0.12]), the presence of a high-grade tumor (mean [SEM] score, 3.54 [0.06]), and the presence of a tumor larger than 10 cm (mean [SEM] score, 3.24 [0.06]) were the most important variables identified by respondents in their decision to recommend systemic chemotherapy (Table 4). Improvement in local control (mean [SEM] score, 2.54 [0.06]), the presence of surgical margins positive for tumor (mean [SEM] score, 2.84 [0.06]), and the presence of tumors 5 to 10 cm in size (mean [SEM] score, 2.85 [0.05]) were the least important. The survival benefit from chemotherapy was considered to be more substantial than that for radiation therapy (mean [SEM] score, 3.17 [0.06]).
Overall, no significant differences in responses were seen in recommending systemic chemotherapy for patients younger than 50 years of age or for any tumor size. Medical oncologists were more likely to recommend systemic chemotherapy for high-grade tumors (mean [SEM] Likert scale score, 3.75 [0.15]), and orthopedic oncologists were more likely to recommend it for synovial sarcoma (mean [SEM] score, 3.73 [0.12]). Medical oncologists were also more likely to attribute an improvement in local control to systemic chemotherapy (mean [SEM] score, 2.91 [0.12]; P = .08) and to recommend it for margins positive for tumor (mean [SEM] score, 3.12 [0.12] P = .03).
Years in practice only influenced the opinion about local control with chemotherapy. Respondents with more than 15 years in practice felt that systemic chemotherapy had a greater effect on local control than those with less than 5 years in practice (mean [SEM] Likert scale score, 2.71 [0.06] vs 2.31 [0.10]; P = .02). Respondents who had greater than 75% of their clinical practice devoted to sarcoma care had differing responses on several of the factors compared with those who had less than 25% of their clinical practice devoted to sarcoma care. They placed more importance on systemic chemotherapy overall (mean [SEM] score, 3.05 [0.12] vs 2.65 [0.07]; P = .014) and on the survival benefit from therapy (mean [SEM] score, 3.32 [0.15] vs 3.00 [0.08]; P = .02). They were also more likely to recommend systemic chemotherapy for tumors larger than 10 cm (mean [SEM] score, 3.58 [0.18] vs 3.03 [0.08]; P = .009) and for patients younger than 50 years of age (mean [SEM] score, 3.29 [0.16] vs 2.86 [0.08]; P = .004).
Although data are available from randomized controlled trials to guide treatment decisions in the multidisciplinary management of STS of the extremities, there is a lack of consensus regarding relative indications for the use of adjuvant radiation therapy and systemic chemotherapy. By studying specialty-specific responses to scenarios on the use of radiation therapy and systemic chemotherapy in the treatment of localized STS, we show that physician specialty is an important factor contributing to variability in treatment recommendations.
The importance of radiation therapy in the management of STS of the extremities was rated highest by radiation oncologists, who were also more likely to assert that radiation therapy is underutilized in the multimodality treatment of patients with STS. Similarly, among all the responding physicians, medical oncologists assigned the greatest importance to systemic chemotherapy, even though, overall, most respondents felt that current utilization was appropriate.
Considerable interspecialty variation was observed with regard to indications for treatment, which suggests that, even among experts, there is a diversity of opinions regarding the multidisciplinary management of STS of the extremities. In general, clinicians’ recommendations tend to be biased in favor of their specialty-specific modality. Although this may seem intuitive, it has not been well studied in the medical literature, in general, or in the sarcoma literature, in particular. Given the preponderance of treatment guidelines and tumor board recommendations that are based on expert opinion rather than level I evidence for a rare disease process such as STS of the extremities, it would seem to be important to deconstruct the process by which clinicians at the individual and group level arrive at treatment recommendations.
Current National Comprehensive Cancer Network guidelines recommend consideration of adjuvant radiation therapy for patients with high-grade STS, with large tumors, or with final margins close to or positive for tumors.11 Our respondents demonstrated the highest agreement across all specialties in cases of STS of the extremities with margins positive for tumor, with a high-grade tumor, with a tumor size of greater than 10 cm, or with a tumor close to a neurovascular bundle. Although respondents rated improvement in local control as a significant benefit of radiation therapy, improvement in overall survival was not. These responses are consistent with the published literature regarding the oncologic benefits of adjuvant radiation therapy.12
However, subtle but important differences emerged when we analyzed the responses by physician specialty. Radiation oncologists were more likely to offer radiation therapy to patients younger than 50 years of age and for tumors 5 to 10 cm in maximal size. Furthermore, they were more inclined to disagree with the statements that radiation therapy is not indicated for radiation-associated STS of the extremities and that radiation therapy is not indicated for low-grade STS of the extremities. These are controversial areas in which specific evidence-based data and guidelines are not available and for which clinicians may have substantially different views of the risk-benefit ratio of treatment.13,14
Overall, respondents viewed chemotherapy as less important than radiation therapy in the multidisciplinary management of STS of the extremities. This appropriately reflects the conflicting nature of data from randomized trials examining the benefits of adjuvant chemotherapy in STS of the extremities. Interestingly, both radiation and surgical oncologists placed less emphasis on a survival benefit with chemotherapy than did medical oncologists and orthopedic oncologists. Medical oncologists felt that chemotherapy played a greater role in local control than did surgical oncologists. These opinions are supported by outcomes data. In the previously quoted meta-analysis of systemic therapy in STS,6 the hazard ratio with adjuvant chemotherapy for local recurrence was 0.73 (95% CI, 0.56-0.95), which corresponds to a 4% reduction in absolute risk. For synovial sarcoma, orthopedic oncologists felt most strongly about recommending chemotherapy, which may be explained by practice patterns (ie, orthopedic oncologists treat a higher proportion of younger patients with bone sarcoma and STS for whom chemotherapy is more routinely administered).
For clinical scenarios in which adjuvant treatment is clearly indicated, such as radiation therapy for large or high-grade STS and chemotherapy for younger patients with favorable subtypes, any lack of agreement by specialists is concerning. Either the current data are felt to be inadequate to inform clinical decision making or there is unfamiliarity with data outside one’s scope of practice. An argument could also be made for better quality studies. Furthermore, if the first point of contact for a patient is a specialist who places less importance on adjuvant therapy, then the treatment algorithm may not progress beyond surgical resection. Our data also point to the importance of a multidisciplinary STS tumor board. Even though individual physicians may have differing opinions about treatment, in aggregate, the best course for the patient will be charted by discussion and consideration of all treatment options. Finally, experience as measured by the percentage of clinical practice devoted to sarcoma care may also influence responses. In particular, physicians who had greater than 75% of their clinical practice devoted to sarcoma care placed more importance on systemic chemotherapy and a potential survival benefit with treatment. They were also more likely to recommend systemic chemotherapy for patients younger than 50 years of age and for tumors larger than 10 cm.
Certain limitations of our study must be acknowledged. Some are related to the survey methods that we used to collect our data. The use of a survey instrument has the inherent limitation of respondent bias because only physicians who were interested or inclined to respond took the time to do so. Although electronic dissemination results in easy and rapid delivery, many e-mail addresses were not valid or had filters, which meant that the survey never arrived to the intended recipient. By opting to only include physicians who were active members of selected oncology societies with a self-declared interest in sarcoma care, we also potentially introduced a selection bias. It is likely that there are additional physicians who treat a substantial number of patients with STS in their clinical practice who were not solicited to participate or who did not participate in this survey. Finally, although statistically significant differences were seen in the mean response rates for many of the questions, whether these translate into meaningful clinical differences is not demonstrated by our data.
To conclude, physician specialty appears to influence recommendations for adjuvant radiation therapy and chemotherapy in STS of the extremities. This bias likely arises from divergent interpretations of published literature and perhaps from a lack of familiarity with data outside of one’s clinical scope of practice. Multidisciplinary clinics and tumor boards may be an effective tool for discussion among different specialties to reach consensus decisions and to minimize variation due to specialty bias. However, the effect of specialty bias on multimodality treatment recommendations of expert panels and tumor boards warrants further study.
Corresponding Author: Nabil Wasif, MD, Department of Surgery, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ 85054 (email@example.com).
Accepted for Publication: December 10, 2012.
Published Online: March 20, 2013. doi:10.1001/jamasurg.2013.113
Author Contributions: Drs Wasif and Canter had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Wasif, Tamurian, Chirstensen, Monjazeb, Canter.
Acquisition of data: Smith, Tamurian, Canter.
Analysis and interpretation of data: Wasif, Smith, Monjazeb, Martinez, Canter.
Drafting of the manuscript: Wasif, Smith, Canter.
Critical revision of the manuscript for important intellectual content: Wasif, Tamurian, Chirstensen, Monjazeb, Martinez, Canter.
Statistical analysis: Wasif.
Administrative, technical, and material support: Tamurian, Canter.
Study supervision: Tamurian, Canter.
Conflict of Interest Disclosures: None reported.
Previous Presentation: This paper was presented at the 82nd Annual Meeting of the Pacific Coast Surgical Association; February 18-21, 2011; Phoenix, Arizona; and is published after peer review and revision.