[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to evaluate the risk of local recurrence and survival after soft tissue sarcoma (STS) resection with positive margins and to evaluate the safety of sparing adjacent critical structures.
[Show abstract][Hide abstract] ABSTRACT: Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS.
From June 1996 to October 2000, eligible patients with resectable RPS were entered onto a phase II trial of preoperative XRT (45-50Gray) plus postoperative BT (20-25Gray). Kaplan Meier survival curves were constructed and compared by log rank analysis (SPSS 21.0).
All 40 patients had preoperative XRT and total gross resection as part of the prospective trial, nineteen received BT (48%). Median follow-up was 106months. For the entire cohort, OS at 5 and 10years was 70% and 64%, respectively; RFS at 5 and 10years was 69% and 63%. RFS was significantly reduced in high versus low grade RPS at 5years (53% vs. 88%, p=0.016), but not at 10years (53% vs. 75%, p=0.079). RFS and OS at 10years were reduced in patients who presented with recurrent compared to primary disease (RFS 30% vs. 74%, p=0.015; OS 36% vs. 76%, p=0.036). At 10years, neither RFS nor OS was improved in patients who received BT compared to those who did not (RFS 56% vs. 69%, p=0.54; OS 52% vs.76%, p=0.23).
In this prospective trial with mature follow-up, long-term OS and RFS in patients who underwent combined preoperative XRT plus resection of RPS compare favourably with those reported in retrospective institutional and population-based series. Postoperative BT was associated with unacceptable toxicity and did not contribute to disease control.
In a prospective trial with mature follow-up, preoperative radiation combined with complete resection of retroperitoneal sarcoma resulted in favourable long-term RFS and OS compared to historical controls. Dose escalation with postoperative brachytherapy was not associated with better disease control.
Radiotherapy and Oncology 01/2014; · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article presents the current understanding of prognostic factors and outcomes for retroperitoneal sarcoma. The discussion focuses on the literature published since 2000, including studies with cohorts of at least 30 patients. An interpretation of factors that have contributed to an improvement in outcomes has been performed. With demonstration of the potential for good long-term outcomes and a better appreciation for the importance of minimizing treatment-related morbidity, the international sarcoma community has increasingly recognized and emphasized the importance of expert multidisciplinary assessment and care for this rare malignancy.
Surgical Oncology Clinics of North America 04/2012; 21(2):317-31. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Radiation-induced soft tissue sarcomas (RI-STS) are rare, and it is believed that they are associated with a poor prognosis.The authors of this report compared the clinical and functional outcomes of adults who had extremity RI-STS with the outcomes of adults with sporadic STS.
Forty-four patients who were diagnosed with RI-STS from 1989 to 2009 were identified from 4 prospectively collected databases. Patient demographics, surgical and adjuvant treatment parameters, and oncologic and functional outcomes were evaluated.
The median latent period from irradiation of the primary condition to RI-STS diagnosis was 16 years. The median radiotherapy dose used for the index condition was 45 gray. The median age at RI-STS diagnosis was 56 years. The most common primary diagnoses were breast cancer (36.4%) and lymphoma (34.1%). The most common RI-STS histologies were malignant fibrous histiocytoma (36.4%) and angiosarcoma (18.2%). Forty-two patients underwent surgery, 13 patients received adjuvant radiotherapy, and 8 patients received adjuvant chemotherapy. Systemic metastases occurred in 50% of treated patients (n = 21), and 26% (n = 11) developed local recurrence, the risk of which was lower among patients who received reirradiation (P = .043). The 5-year disease-free interval (DFI) and overall survival (OS) rates for patients with RI-STS who presented without metastasis were 36% and 44%, respectively. Patients who had International Union Against Cancer TNM stage III RI-STS had a significantly worse DFI compared with patients who had stage III sporadic STS (multivariate analysis, P = .051). Eighteen patients with RI-STS underwent functional assessment after surgery, and their results were comparable to those of patients with sporadic STS.
Despite aggressive surgical treatment, patients who have RI-STS remain at greater risk of both local and systemic recurrence compared with patients who have sporadic STS, but they can anticipate similar functional outcomes. Reirradiation can be relatively safe and effective if used properly.
Cancer 10/2011; 118(10):2682-92. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the effect of age on the recurrence of soft tissue sarcoma in the extremities and trunk.
This was a multicenter study that included 2,385 patients with median age at surgery of 57 years. The end points considered were local recurrence and metastasis. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors.
Older patients presented with tumors that were larger (P < .001) and of higher grade (P < .001). The proportion of positive margins increased significantly as patients age (P < .001), but radiation therapy was relatively underused in patients older than age 60 years. The 5-year cumulative incidences of local recurrence were 7.2% (95% CI, 4% to 11.7%) for patients age 30 years or younger and 12.9% (95% CI, 9.1% to 17.5%) for patients age 75 years or older. The corresponding 5-year cumulative incidences of metastasis were 17.5% (95% CI, 12.1% to 23.7%) and 33.9% (95% CI, 28.1% to 39.8%) for the same groups. Regression models showed that age was significantly associated with local recurrence (P < .001) and metastasis (P < .001) in nonadjusted models. After adjusting for imbalance in presentation and treatment variables, age remained significantly associated with local recurrence (P = .031) and metastasis (P = .019).
Older patients have worse outcomes because they tend to present with worse tumors and are treated less aggressively. However, there remained a significant increase in the risk of both local and systemic recurrence associated with increasing age that could not be explained by tumor or treatment characteristics.
Journal of Clinical Oncology 09/2011; 29(30):4029-35. · 18.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To quantify the effect of delineation method on bladder DVH, observer variability (OV) and contouring time for prostate IMRT plans.
Planning CT scans and IMRT plans of 30 prostate cancer patients were anonymized. For 20 patients, 1 observer delineated the bladder using 9 methods. The effect of delineation method on the DVH curve, discrete dose levels and delineation time was quantified. For the 10 remaining CTs, 6 observers delineated bladder wall using 4 methods. Observer-based volume variation and intraclass correlation coefficient (ICC) were used to describe the dosimetric effects of OV.
Manual delineation of the bladder wall (BW_m) was significantly slower than any other method (mean: 20 min vs. ≤ 13 min) and the dosimetric effect of OV was significantly larger (V70 Gy ICC: 0.78 vs. 0.98). Only volumes created using a 2.5mm contraction from the outer surface, and a method providing a consistent wall volume, showed no notable dosimetric differences from BW_m in both absolute and relative volume.
Automatic contractions from the outer surface provide quicker, more reproducible and reasonably accurate substitutes for BW_m. The widespread use of automatic contractions to create a bladder wall volume would assist in the consistent application of IMRT dose constraints and the interpretation of reported dose.
Radiotherapy and Oncology 08/2011; 101(3):479-85. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the geometric relationship between local recurrence (LR) and external beam radiotherapy (RT) volumes for soft-tissue sarcoma (STS) patients treated with function-preserving surgery and RT.
Sixty of 768 (7.8%) STS patients treated with combined therapy within our institution from 1990 through 2006 developed an LR. Thirty-two received preoperative RT, 16 postoperative RT, and 12 preoperative RT plus a postoperative boost. Treatment records, RT simulation images, and diagnostic MRI/CT data sets of the original and LR disease were retrospectively compared. For LR location analysis, three RT target volumes were defined according to the International Commission on Radiation Units and Measurements 29 as follows: (1) the gross tumor or operative bed; (2) the treatment volume (TV) extending 5 cm longitudinally beyond the tumor or operative bed unless protected by intact barriers to spread and at least 1-2 cm axially (the TV was enclosed by the isodose curve representing the prescribed target absorbed dose [TAD] and accounted for target/patient setup uncertainty and beam characteristics), and (3) the irradiated volume (IRV) that received at least 50% of the TAD, including the TV. LRs were categorized as developing in field within the TV, marginal (on the edge of the IRV), and out of field (occurring outside of the IRV).
Forty-nine tumors relapsed in field (6.4% overall). Nine were out of field (1.1% overall), and 2 were marginal (0.3% overall).
The majority of STS tumors recur in field, indicating that the incidence of LR may be affected more by differences in biologic and molecular characteristics rather than aberrations in RT dose or target volume coverage. In contrast, only two patients relapsed at the IRV boundary, suggesting that the risk of a marginal relapse is low when the TV is appropriately defined. These data support the accurate delivery of optimal RT volumes in the most precise way using advanced technology and image guidance.
International journal of radiation oncology, biology, physics 06/2011; 82(4):1528-34. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to characterize the accuracy of a novel in-house optical tracking system (OTS), and to determine its efficiency for daily pre-treatment positioning of pelvic radiotherapy patients compared to conventional optical distance indicator (ODI) methodology. The OTS is comprised of a passive infrared stereoscopic camera, and custom control software for use in assisting radiotherapy patient setup. Initially, the system was calibrated and tested for stability inside a radiation therapy treatment room. Subsequently, under an ethics approved protocol, the clinical efficiency of the OTS was compared to conventional ODI setup methodology through 17 pelvic radiotherapy patients. Differences between orthogonal source-to-skin distance (SSD) readings and overall set-up time resultant from both systems were compared. The precision of the OTS was 0.01 ± 0.01 mm, 0.02 ± 0.02 mm, and -0.01 ± 0.06 mm in the left/right (L/R), anterior/posterior (A/P), and cranial/caudal (C/C) directions, respectively. Discrepancies measured between the linac radiographic center in the treatment room and the calibrated origin of the camera (OTS) by two independent observers was submillimeter. Analysis of 146 fractions from 17 patients showed a high correlation between the SSD readings of the OTS and ODI setup methodologies (r = 0.99). The average time for pre-treatment positioning using the OTS couch shift calculation was 2.60 ± 0.69 minutes, and for conventional ODI setup, 3.62 ± 0.82 minutes; the difference of 1.02 minutes was statistically significant (p < 0.001). In conclusion, the OTS is a precise and robust tool for use as an independent check of treatment room patient positioning. The system is indicated as geometrically equivalent to current methods of daily pre-treatment patient positioning with potential for gains in efficiency by decreasing setup times in the treatment room.
Technology in cancer research & treatment 04/2011; 10(2):163-70. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report an unusual case of a primary osteosarcoma of the lung in an asymptomatic 77-year-old male, who underwent lobectomy with complete resection of the lung lesion. His pattern of relapse was to multiple lymph nodes. The first relapse was 11 weeks after lobectomy in subcarinal lymph nodes, confirmed on needle aspiration to be consistent with sarcoma. Given his excellent performance status, this was treated with radical radiotherapy to 70 Gy in 35 fractions with good control. He relapsed to other lymph node regions. A biopsy of the external iliac lymph node was done and revealed osteoid production, consistent with osteosarcoma. He received palliative radiotherapy to several nodal areas with good clinical response. We review the literature of this rare tumor with an unusual pattern of relapse.
International Journal of Clinical Oncology 02/2011; 16(1):67-70. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to assess patient, tumor, and treatment factors that affected overall survival in a group of patients who underwent surgery for soft tissue sarcoma (STS) and presented with American Joint Commission on Cancer stage IV disease.
A retrospective review was undertaken of a single institution's database from the years 1986 to 2006 in all patients who met the following inclusion criteria: 1) surgical management of the primary tumor was undertaken, and 2) metastatic disease was present at the time of initial presentation. In total, 112 patients were identified who met the inclusion criteria.
The 5-year survival rate for the entire group was 17%. In univariate analysis, the variables that were identified as statistically significant for predicting improved overall survival were resection of metastatic disease (P = .003), <4 pulmonary metastases (P = .05), and the presence of lymph node metastases versus pulmonary metastases (P = .0002). In multivariate analysis, only the presence of lymph node metastases versus pulmonary metastases retained statistical significance (P = .05). The 5-year survival rate for patients who had lymph nodes metastases at diagnosis was 59%, whereas it was only 8% for patients who presented with pulmonary metastases.
Patients who presented with metastatic STS had a very poor prognosis despite aggressive surgical management of their primary tumor. The current results indicated that, although patients with isolated lymph node metastases may be cured by surgical resection, patients with pulmonary metastases are unlikely to be cured even with aggressive surgical management and should be treated with palliation of symptoms as the main objective.
Cancer 01/2011; 117(2):372-9. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15-76) and 14 (range 0.4-18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to quantify residual interfraction displacement of seminal vesicles (SV) and investigate the efficacy of rotation correction on SV displacement in marker-based prostate image-guided radiotherapy (IGRT). We also determined the effect of marker registration on the measured SV displacement and its impact on margin design.
SV displacement was determined relative to marker registration by using 296 cone beam computed tomography scans of 13 prostate cancer patients with implanted markers. SV were individually registered in the transverse plane, based on gray-value information. The target registration error (TRE) for the SV due to marker registration inaccuracies was estimated. Correlations between prostate gland rotations and SV displacement and between individual SV displacements were determined.
The SV registration success rate was 99%. Displacement amounts of both SVs were comparable. Systematic and random residual SV displacements were 1.6 mm and 2.0 mm in the left-right direction, respectively, and 2.8 mm and 3.1 mm in the anteroposterior (AP) direction, respectively. Rotation correction did not reduce residual SV displacement. Prostate gland rotation around the left-right axis correlated with SV AP displacement (R(2) = 42%); a correlation existed between both SVs for AP displacement (R(2) = 62%); considerable correlation existed between random errors of SV displacement and TRE (R(2) = 34%).
Considerable residual SV displacement exists in marker-based IGRT. Rotation correction barely reduced SV displacement, rather, a larger SV displacement was shown relative to the prostate gland that was not captured by the marker position. Marker registration error partly explains SV displacement when correcting for rotations. Correcting for rotations, therefore, is not advisable when SV are part of the target volume. Margin design for SVs should take these uncertainties into account.
International journal of radiation oncology, biology, physics 09/2010; 80(2):590-6. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For patients with an extremity soft tissue sarcoma (STS) treated with preoperative radiotherapy and surgically excised with positive margins, we retrospectively reviewed whether a postoperative radiation boost reduced the risk of local recurrence (LR).
A total of 216 patients with positive margins after resection of an extremity STS treated between 1986 and 2003 were identified from our institution's prospectively collected database. Patient demographics, radiation therapy parameters including timing and dose, classification of positive margin status, reasons for not administering a postoperative boost, and oncologic outcome were collected and evaluated.
Of the 216 patients with a positive surgical margin, 52 patients were treated with preoperative radiation therapy alone (50 Gy), whereas 41 received preoperative radiation therapy plus a postoperative boost (80% received 16 Gy postoperatively for a total of 66 Gy). There was no difference in baseline tumor characteristics between the two groups. Six of 52 patients in the group receiving preoperative radiation alone developed a LR compared with 9 of 41 in the boost group. Five-year estimated LR-free survivals were 90.4% and 73.8%, respectively (p = 0.13).
We found that including the postoperative radiation boost after preoperative radiation and a margin-positive excision did not provide an advantage in preventing LR for patients treated with external beam radiotherapy. Given that higher radiation doses placed patients at greater risk for late complications such as fracture, fibrosis, edema, and joint stiffness, judicious avoidance of the postoperative boost while maintaining an equivalent rate of local control can reduce the risk of these difficult-to-treat morbidities.
International journal of radiation oncology, biology, physics 07/2010; 77(4):1191-7. · 4.59 Impact Factor