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21 September 2015

Radiotherapy Associated with Improved Survival for High-Grade Sarcoma of the Extremity

Title:

Radiotherapy Associated with Improved Survival for High-Grade Sarcoma of the Extremity

 

Authors:

Swapnil D. Kachare, MD, MBA1

Jason Brinkley, PhD2

Nasreen A. Vohra, MD1

Emmanuel E. Zervos, MD1

Jan H. Wong, MD1

Timothy L. Fitzgerald, MD1

 

Affiliations:

1The Brody School of Medicine, East Carolina University, Division of Surgical Oncology, Department of Surgery

 

2College of Allied Health, East Carolina University, Department of Biostatistics

 

Running head:

Radiotherapy for Extremity Sarcoma

 

Disclosures/Funding:

None

 

Presentation:

Presented at the 67th Annual Society of Surgical Oncology Cancer Symposium, Phoenix, AZ

 

Text Pages: 15            Tables: 5         Figures: 3 (1a, 1b & 2)

 

Corresponding author:

Timothy L. Fitzgerald

Brody School of Medicine, 4S24

600 Moye Boulevard

Greenville, NC

27834

Phone: 252/744-4110

Fax: 252/744-5777

Email: fitzgeraldt@ecu.edu

 

Summary- In order to define the impact of the use and timing of radiation therapy on survival for extremity sarcoma we reviewed data from a large cancer registry.  These data demonstrated that radiotherapy, regardless of the timing, is associated with improved survival in high-risk sarcoma. 

 

Background: The impact of radiotherapy on local control in limb-preserving surgery for high-risk sarcoma has been well studied.  However, the impact of the use and timing of radiation therapy on survival is unclear.

 

Methods: From 1988 to 2010, patients with Stage III extremity sarcoma were identified within the SEER registry and cohorts were created using propensity score matching between irradiated and non-irradiated groups.

 

Results: A total of 2,606 patients were identified, with a median age of 59 years a majority were white (81%), male (54%), received radiotherapy (78%), and had lower extremity (80%) sarcomas.  The most common subtype was fibrohistiocytic (29.8%).  Patients treated with radiotherapy were younger (57.2 vs. 60.3 years) and differed in subtype compared to those untreated.  The matched cohorts were better balanced for all factors.  Radiation therapy was associated with a 5% 5-year survival advantage on univariate analysis for both the unmatched (p = 0.002) and matched cohorts (p = 0.01). On multivariate analysis radiotherapy was associated with a 20% and 30% survival advantage for the matched and unmatched cohorts, respectively (p ≤ 0.02).  The timing of radiotherapy did not affect survival.

 

Conclusions: Radiotherapy, regardless of the timing, is associated with improved survival in high-risk sarcoma.  

 

Keywords:

Radiotherapy, Sarcoma, Extremity, Adjuvant, Neoadjuvant, Radiation therapy, soft tissue sarcoma

 

The modern era of limb-preserving treatment for extremity sarcoma was ushered in by a landmark radiotherapy trial conducted at the National Institutes of Health (NIH).1  In this trial, no difference in survival was noted for 43 patients with high-grade soft tissue sarcomas of the extremities randomized to receive amputation versus limb-sparing resection plus adjuvant radiation therapy.  These findings have been replicated in several large retrospective series.23

 

Even though radiotherapy is known to improve local control in high-risk extremity sarcoma, it is unclear whether this translates into a survival advantage.  Improved local control in other cancers, such as breast cancer, rectal cancer, and melanoma, has been associated with modest improvements in survival.4-6  However, no single study clearly demonstrates a survival advantage with the use of adjuvant radiotherapy for extremity sarcoma.  It is likely that these relatively small studies are underpowered to definitively demonstrate a modest survival advantage.

 

Investigators from the NCI reported, in a 20-year follow-up of a prospective randomized trial, an improvement in local control and a trend towards improved survival with the use of limb-sparing surgery plus radiotherapy versus limb-sparing surgery alone. However, the authors acknowledged this study was underpowered to demonstrate a <20% improvement in survival.7  A trial from Memorial Sloan Kettering randomizing patients with extremity and trunk sarcomas to surgery with or without brachytherapy demonstrated that radiotherapy was associated with improved local control, but had no survival advantage.7  Pisters et al. had similar findings in a randomized trial of patients with high-grade sarcoma8  In contrast; a retrospective analysis by Ueda found that multimodal therapy, including radiation, was associated with a survival advantage.9

 

Sequencing of radiotherapy may also affect outcomes for patients with soft tissue sarcoma.  Investigators from the University of Toronto reported the results of a prospective trial involving 190 patients with extremity sarcoma undergoing limb preserving procedures randomized to preoperative versus postoperative radiotherapy.10  The study was terminated early secondary to an increased wound complication rate in the preoperative group.  However, long-term follow-up demonstrated better limb function with preoperative treatment.11  Interestingly, a slight survival advantage was noted for patients treated with preoperative radiotherapy, ~3% at 3 years.10  Other investigators have reported similar findings for wound infection rates and function, with no difference in survival.12

 

To better define the use and impact of radiotherapy on patients with extremity sarcoma, we conducted a propensity matched cohort study of sarcoma patients in the SEER database. The study was confined to patients with high-risk neoplasm, >5 cm and high grade, without systemic metastasis (Stage III).  This group was chosen because of the clear impact of radiotherapy on local recurrence.  Several investigators have demonstrated little advantage of radiotherapy in the treatment of sarcomas smaller than 5 cm regardless of grade.813-15  We hypothesized that improved local control imparted by radiotherapy in this high-risk group will translate into an improvement in survival.

 

Materials and Methods

Data Source, Patient Selection, and Exclusion Criteria

Patients diagnosed with extremity sarcoma were identified in the Surveillance Epidemiology and End Results (SEER) tumor registry.  Currently, the SEER registry represents 28% of the U.S. population.16  A query of the SEER registry using SEER*Stat 8.1.2 was performed to identify patients’ diagnosed with sarcoma from 1988 to 2010.  Tumor characteristics including primary site location, tumor grade, histology, extent of disease (local, regional, or distant), size of the primary tumor, and nodal status were identified within either the SEER historic stage A (1980–2008), extent of disease (EOD) (1988–2003), or collaborative stage (CS) (2004–2008) systems.  Treatment data included surgery to the primary site and use and timing of radiation therapy.  The American Joint Committee on Cancer (AJCC) 7th Edition, Soft Tissue Sarcoma Staging was utilized to derive a final pathologic TNM classification.  Stage III patients were identified as those with tumor >5 cm in greatest dimension and high-grade.  We exclude Stage III patients with node positive disease.


Patients were excluded if they had non-extremity sarcomas (n = 58,369), Kaposi sarcomas (n = 16,959), non-soft tissue sarcomas (n = 3,891), metastatic disease, unknown size and/or unknown tumor grade (n = 11,623).  Also, those patients who did not undergo surgery (n = 346), had an amputation (n = 1,064), had unknown sequence of radiation (n = 88), or unknown cause of death (n = 920) were excluded.

 

Survival Analysis and Propensity Matching

The unmatched dataset consisted of all patients meeting inclusion criteria.  Propensity scores were calculated using radiotherapy, age, gender, race, tumor subtype, and location (upper vs. lower limb).  Output propensity scores were then matched using a SAS® macro as previously reported.4,17,18.  Two separate propensity score cohorts were created.  In the first, a 1:1 matched cohort of patients who received radiation therapy and those who underwent surgery alone was created.  The second propensity score matched cohort included only those who received radiotherapy with a 1:1 matching for neoadjuvant and adjuvant radiation therapy.

 

Statistical Analysis

Univariate descriptive analyses were performed with Student’s t-tests and chi-squared tests as indicated.  Logistic regression was performed to assess use of radiotherapy over time.  Survival was analyzed using Kaplan–Meier technique, log-rank test, and Cox regression.  Data analysis was performed using a combination of the SAS® version 9.3 and JMP® Pro version 10.0.0; 2012 (SAS Institute Inc., Cary, NC, USA).

 

Results

Demographics

We identified 2,606 patients with Stage III extremity sarcoma.  The median age was 59 years.  The majority was white (81%), male (54%), received radiotherapy (78%), and had tumors located in the lower extremity (80%).  The most common World Health Organization histologic subtype was fibrohistiocytic (29.8%).  In the overall cohort, there was an imbalance between patients treated with radiotherapy and those treated with surgery alone.  The median age was significantly older for those who did not receive radiotherapy (60.3 vs. 57.2 years), and the use of radiotherapy differed by histologic subtype.  Given the unbalanced nature of the groups, we performed matching using propensity scores. A total of 1,162 comprised the matched cohort, 581 in both the radiation and non-radiation groups. (Table 1)

 

Survival

On univariate analysis of the unmatched cohort, we found that use of radiation therapy was associated with a significant 5-year survival advantage (65 vs. 60%, p = 0.002). (Figure 1a) This is similar to the non-significant finding reported in the long-term follow-up of the NCI study discussed above.  In addition, there was also a survival advantage for women (68 vs. 61%, p=0.008).  Five-year disease-specific survival was also predicated on histologic subtype, such that the highest survival was associated with liposarcoma (73%) and lowest for leiomyosarcoma (54%).  On Cox regression younger age, use of radiotherapy and female gender were associated with a survival advantage. (Table 2)

 

Given the unbalanced characteristics in the unmatched cohort, we performed similar survival analyses in the propensity score mahed cohort.  As in the unmatched cohort, radiotherapy continued to be associated with a 5-year disease-specific survival advantage of 65 versus 60%, p=0.01. (Figure 1b) Women also continued to have a superior 5-year survival (66 vs. 59%, p=0.04).  However, race, histologic subtype, and location were not associated with survival.  On Cox regression, advanced age (p<0.0001), male gender (RR = 1.32, p = 0.01) and omission of radiotherapy (RR = 1.30, p = 0.01) were associated with diminished survival.  In the matched cohort, histologic subtype was also independently associated with survival. (Table 3)  In order to better understand weather or not the sample sized in the matched group was adequate to determine a survival advantage we performed a power analysis.  Using uncensored median overall survival for the study groups (51 months with XRT and 46 months without) and the standard deviation for this group (47) setting the  p value at 0.05 and power at 0.8 a sample size of 1093 patients would be required to detect a significant difference.


Survival for patients treated with radiotherapy

In order to examine the survival differences related to the timing of radiation therapy, we compared patients treated with neoadjuvant radiotherapy to those treated with adjuvant radiotherapy. A total of 2,025 patients were treated with radiotherapy in the unmatched cohort.  In this cohort, gender, race, and histologic subtype were all associated with survival.  However, there was no association between timing of radiotherapy and survival.  In a Cox regression model, advanced age, gender, and histologic subtype continued to be associated with survival. (Table 4) In order to clearly define these relationships, we again performed a matched cohort design.  In this subset, we matched patients for age, timing of radiation, histologic subtype, extremity location, race, and gender.  The matched cohort consisted of 1,094 patients.  In this matched cohort, survival was not associated with gender, race, location, histologic subtype, or timing of radiotherapy.  On Cox regression, only advanced age and histologic subtype were associated with survival.

 

Delivery of Radiotherapy

In order to define patterns of radiation treatment, we plotted radiotherapy use over time.  On average, 23% of patients between the years 1988 and 2010 did not receive adjuvant radiotherapy. (Figure 2) Use of radiation was consistent over time, R2 = 0.07.  However, in patients who were treated with radiation therapy, there was an increase in the use of neoadjuvant treatment subsequent to the publication of long-term functional outcomes by the University of Toronto sarcoma group.  Prior to 2002, there was no increase in the use of neoadjuvant therapy over time, R2=0.02.  However, following 2002, there was a marked increase in the use of neoadjuvant treatment with an R2=0.76.

 

Discussion

Work from investigators at the National Institutes of Health (NIH) and other sites ushered in the era of limb preservation for extremity sarcoma by demonstrating that survival was equivalent whether patients were treated with amputation or radical excision combined with adjuvant radiotherapy.1-3  In addition, randomized trials demonstrate that adjuvant radiotherapy improves local control for extremity sarcoma when compared to surgery alone.7819  This benefit is greatest for tumors larger than 5 cm that are high grade.8913  Based upon these and other data, the National Comprehensive Cancer Network (NCCN) currently recommends that radiation be considered in all Stages IIB and III extremity sarcomas.20  Although the impact of radiation on local control for extremity sarcoma has been well studied, the effects of local control on survival are less well understood.

Multiple small prospective, randomized, and retrospective single institutional cohort studies have examined the question of survival benefit for adjuvant radiotherapy in extremity sarcoma.  None, however, have been sufficiently powered to detect a small survival advantage.19  After 17 years of follow-up, an NCI trial randomizing 141 patients to either adjuvant radiation therapy with surgical resection or radial resection alone demonstrated a trend toward improved survival in the treatment arm that failed to reach statistical significance.19  The authors acknowledge that this study was underpowered to demonstrate a survival advantage of <20%.  Other studies, with shorter follow-up, report similar findings.7821-23  Most of these trials include patients with both low-risk and high-risk extremity sarcomas.  Two studies of the SEER registry database have attempted to address this issue.  Al-Refaie found on multivariate analysis of 1,618 patients with T1 extremity sarcomas (<5 cm in size) there was no benefit to radiotherapy regardless of grade.15   The authors, however, did not examine the effects of radiotherapy in higher risk patients, as is done in the analysis presented here. In a similar SEER cohort, Schreiber analyzed a cohort of 983 patients with high-grade sarcoma of any size.24    The authors found a survival benefit at 3 years for patients with high-grade tumors >5 cm treated with radiotherapy but no benefit for those with neoplasms < 5cm in size.  In contrast to this study, we examine only high risk patients (> 5 cm and high grade) and match patient using propensity scores.  Discrepancies in these trials are likely secondary to variation of how high-risk sarcoma is defined and imbalance between treatment groups.

 

Because a prospective randomized trial with sufficient power to address the impact of radiotherapy on survival for high-risk extremity sarcoma is unlikely, it is imperative to address this issue in an alternative manner.  In this study, we restricted our cohort to patients with Stage III (>5 cm and high grade) disease as this group has a clear local control benefit with adjuvant radiotherapy.  In order to minimize bias secondary to imbalances between comparison groups, we performed a propensity score cohort matching.  Propensity score matching can mitigate bias, is ideal for large nonrandomized datasets, and can increase confidence in the strength of observed outcomes.25-27  In this study, we analyzed survival difference in both matched and unmatched cohorts with Stage III extremity sarcoma.  We found a consistent survival benefit in high-risk sarcoma on univariate and multivariate analysis in both matched and unmatched cohorts.  These data are similar to small survival advantages seen with improved local control reported in breast and rectal cancer.56 

 

Timing of radiotherapy may also affect outcome for extremity sarcoma.  In a prospective trial involving 190 patients with extremity sarcoma randomized to preoperative or postoperative radiotherapy from the Toronto Sarcoma Group, investigators found an increase in postoperative wound complication is the preoperative treatment group and no difference in local recurrence.10  Long-term follow-up demonstrated improved outcomes in the preoperative treatment group with superior limb function secondary to fewer instances of fibrosis, joint stiffness, and edema.1128 Interestingly, in this small trial, patients receiving preoperative radiation therapy were noted to have significant improvement in overall survival.10  In order to examine the survival differences related to the timing of radiation therapy we compared patients treated with neoadjuvant radiation to those treated with adjuvant radiation.  Using a similar propensity score matching methodology as outlined above, we found no difference in survival between patients who underwent preoperative and postoperative radiation treatment.  There was an increase in the use of preoperative radiation therapy subsequent to the 2002 publication from the Toronto Sarcoma group.

 

Despite the unequivocal recommendation for adjuvant radiotherapy in patients with Stage III sarcoma, a significant proportion of these patients fail to receive recommended treatment.  Aside from histologic subtype and older age, we found no other predictors for omission of radiation therapy.  Multiple previous studies have demonstrated that new practice guidelines often take more than a decade to be integrated into clinical practice.16  Similar to our findings, Bagaria found that 60% of patients with Stages II and III sarcomas fail to receive recommended adjuvant radiotherapy.29  Lack of adoption of evidence-based guidelines has also been noted for multiple other malignancies including rectal and colon cancer,1630-32 but the reason for such practices are unclear.  Other factors identified in the SEER registry that contribute to under treatment include lower socioeconomic status, race, and location (urban vs. rural).163133  Our data suggest that further analysis of treatment disparities for patients with extremity sarcoma is warranted. 


There are inherent limitations to any analysis of the SEER registry as these data are retrospective and rely on the accuracy of local reporting.  The SEER registry does not provide data on the use of chemotherapy, which limits conclusions regarding factors associated with radiation and survival.  In addition, other factors, such as comorbidities, superficial or deep location, and patient choice may impact clinical decision making and are not available in this dataset.  However, propensity matching does control for unmeasured factors that may impact survival and thus more accurately assesses the impact of radiotherapy on sarcoma-specific survival.

 

Conclusions: It is unlikely that a prospective randomized trial with adequate statistical power to analyze the impact of radiotherapy on survival for high-risk extremity sarcoma will be forthcoming.  The results of our study demonstrate a statistically significant survival advantage afforded by the addition of radiotherapy to surgical resection for high-risk extremity sarcoma.  This benefit was similar regardless of whether this radiotherapy was delivered in a neoadjuvant or postoperative, adjuvant fashion.  Unfortunately, nearly 25% of patients with high-risk sarcomas failed to receive recommended radiotherapy, despite clear guidelines recommending its use in this patient population.

 

 

References

1.            Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker A, Brennan M, DeMoss EV, Seipp C, Sindelar WF, Sugarbaker P, Wesley R: The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy, Annals of surgery 1982, 196:305-315

2.            Alamanda VK, Crosby SN, Archer KR, Song Y, Schwartz HS, Holt GE: Amputation for extremity soft tissue sarcoma does not increase overall survival: a retrospective cohort study, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2012, 38:1178-1183

3.            Williard WC, Hajdu SI, Casper ES, Brennan MF: Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity, Annals of surgery 1992, 215:269-275

4.            Kachare SD, Brinkley J, Wong JH, Vohra NA, Zervos EE, Fitzgerald TL: The influence of sentinel lymph node biopsy on survival for intermediate-thickness melanoma, Annals of surgical oncology 2014, 21:3377-3385

5.            Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y: Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials, Lancet 2005, 366:2087-2106

6.            Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB, Jr., Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B: Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02, Journal of the National Cancer Institute 2000, 92:388-396

7.            Brennan MF, Hilaris B, Shiu MH, Lane J, Magill G, Friedrich C, Hajdu SI: Local recurrence in adult soft-tissue sarcoma. A randomized trial of brachytherapy, Arch Surg 1987, 122:1289-1293

8.            Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF: Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma, Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1996, 14:859-868

9.            Ueda T, Aozasa K, Tsujimoto M, Hamada H, Hayashi H, Ono K, Matsumoto K: Multivariate analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma, Cancer 1988, 62:1444-1450

10.          O'Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, Wunder J, Kandel R, Goddard K, Sadura A, Pater J, Zee B: Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial, Lancet 2002, 359:2235-2241

11.          Davis AM, O'Sullivan B, Turcotte R, Bell R, Catton C, Chabot P, Wunder J, Hammond A, Benk V, Kandel R, Goddard K, Freeman C, Sadura A, Zee B, Day A, Tu D, Pater J: Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 2005, 75:48-53

12.          Cheng EY, Dusenbery KE, Winters MR, Thompson RC: Soft tissue sarcomas: preoperative versus postoperative radiotherapy, Journal of surgical oncology 1996, 61:90-99

13.          Geer RJ, Woodruff J, Casper ES, Brennan MF: Management of small soft-tissue sarcoma of the extremity in adults, Arch Surg 1992, 127:1285-1289

14.          Pisters PW, Pollock RE, Lewis VO, Yasko AW, Cormier JN, Respondek PM, Feig BW, Hunt KK, Lin PP, Zagars G, Wei C, Ballo MT: Long-term results of prospective trial of surgery alone with selective use of radiation for patients with T1 extremity and trunk soft tissue sarcomas, Annals of surgery 2007, 246:675-681; discussion 681-672

15.          Al-Refaie WB, Habermann EB, Jensen EH, Tuttle TM, Pisters PW, Virnig BA: Surgery alone is adequate treatment for early stage soft tissue sarcoma of the extremity, The British journal of surgery 2010, 97:707-713

16.          Fitzgerald TL, Zervos E, Wong JH: Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer, Journal of cancer epidemiology 2013, 2013:408460

17.          Perraillon MC: Matching with Propensity Scores to Reduce Bias in Observational Studies. Edited by Burlington, MA, 2006, p. pp. 1-10

18.          D'Agostino RH: Propensity score methods for bias reduction in the comparison of a treatment of a non-randomized control group, Statist Med 1998, 17:2265-2281

19.          Beane JD, Yang JC, White D, Steinberg SM, Rosenberg SA, Rudloff U: Efficacy of adjuvant radiation therapy in the treatment of soft tissue sarcoma of the extremity: 20-year follow-up of a randomized prospective trial, Annals of surgical oncology 2014, 21:2484-2489

20.          Demetri GD, Pollock R, Baker L, Balcerzak S, Casper E, Conrad C, Fein D, Hutchinson R, Schupak K, Spiro I, Wagman L: NCCN sarcoma practice guidelines. National Comprehensive Cancer Network, Oncology (Williston Park) 1998, 12:183-218

21.          Fleming JB, Berman RS, Cheng SC, Chen NP, Hunt KK, Feig BW, Respondek PM, Yasko AW, Pollack A, Patel SR, Burgess MA, Papadopoulos NE, Plager C, Zagars G, Benjamin RS, Pollock RE, Pisters PW: Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas, Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1999, 17:2772-2780

22.          Alektiar KM, Velasco J, Zelefsky MJ, Woodruff JM, Lewis JJ, Brennan MF: Adjuvant radiotherapy for margin-positive high-grade soft tissue sarcoma of the extremity, International journal of radiation oncology, biology, physics 2000, 48:1051-1058

23.          Khanfir K, Alzieu L, Terrier P, Le Pechoux C, Bonvalot S, Vanel D, Le Cesne A: Does adjuvant radiation therapy increase loco-regional control after optimal resection of soft-tissue sarcoma of the extremities?, Eur J Cancer 2003, 39:1872-1880

24.          Schreiber D, Rineer J, Katsoulakis E, Sroufe RL, Lange CS, Nwokedi E, Schwartz D, Choi K, Rotman M: Impact of postoperative radiation on survival for high-grade soft tissue sarcoma of the extremities after limb sparing radical resection, American journal of clinical oncology 2012, 35:13-17

25.          Reeve BB, Smith AW, Arora NK, Hays RD: Reducing bias in cancer research: application of propensity score matching, Health care financing review 2008, 29:69-80

26.          Abdollah F, Sun M, Schmitges J, Tian Z, Jeldres C, Briganti A, Shariat SF, Perrotte P, Montorsi F, Karakiewicz PI: Cancer-specific and other-cause mortality after radical prostatectomy versus observation in patients with prostate cancer: competing-risks analysis of a large North American population-based cohort, European urology 2011, 60:920-930

27.          Kachare SD, Wong JH, Vohra NA, Zervos EE, Fitzgerald TL: Sentinel lymph node biopsy is associated with improved survival in Merkel cell carcinoma, Annals of surgical oncology 2014, 21:1624-1630

28.          Davis AM, O'Sullivan B, Bell RS, Turcotte R, Catton CN, Wunder JS, Chabot P, Hammond A, Benk V, Isler M, Freeman C, Goddard K, Bezjak A, Kandel RA, Sadura A, Day A, James K, Tu D, Pater J, Zee B: Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma, Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2002, 20:4472-4477

29.          Bagaria SP, Ashman JB, Daugherty LC, Gray RJ, Wasif N: Compliance with National Comprehensive Cancer Network guidelines in the use of radiation therapy for extremity and superficial trunk soft tissue sarcoma in the United States, Journal of surgical oncology 2014, 109:633-638

30.          Bradley CJ, Given CW, Dahman B, Fitzgerald TL: Adjuvant chemotherapy after resection in elderly Medicare and Medicaid patients with colon cancer, Archives of internal medicine 2008, 168:521-529

31.          Fitzgerald TL, Biswas T, O'Brien K, Zervos EE, Wong JH: Neoadjuvant radiotherapy for rectal cancer: adherence to evidence-based guidelines in clinical practice, World journal of surgery 2013, 37:639-645

32.          Fitzgerald TL, Lea SC, Atluri PM, Brinkley J, Zervos EE.  Insurance Payer Status and Race Explains Much of the Variability in Colorectal Cancer Survival. J Cancer Therapy 2014 5(13):1223-33

33.          Fitzgerald TL, Bradley CJ, Dahman B, Zervos EE: Gastrointestinal malignancies: when does race matter?, Journal of the American College of Surgeons 2009, 209:645-652

 

Figure Legends


Figure 1:  Sarcoma-specific survival for patients with stage III extremity sarcoma, SEER 1988-2010

  1. Unmatched Cohort: With and without use of radiotherapy
  2. Matched Cohort: With and without use of radiotherapy

Figure 2:  Treatment with radiotherapy for extremity sarcoma, SEER 1988-2010