Yen-Lin Chen

Harvard Medical School, Boston, Massachusetts, United States

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Publications (24)87.01 Total impact

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    ABSTRACT: To compare outcomes of patients with retroperitoneal or pelvic sarcoma treated with perioperative radiation therapy (RT) versus those treated without perioperative RT. RT for retroperitoneal or pelvic sarcoma is controversial, and few studies have compared outcomes with and without RT. Prospectively maintained databases were reviewed to retrospectively compare patients with primary retroperitoneal or pelvic sarcoma treated during 2003-2011. Multivariate Cox regression models were used to assess associations with the primary endpoints: local recurrence-free survival (LRFS) and disease-specific survival. At 1 institution, 172 patients were treated with surgery alone, whereas at another institution 32 patients were treated with surgery and perioperative proton beam RT or intensity-modulated RT with or without intraoperative RT. The groups were similar in age, tumor size, grade, and margin status (all P > 0.08). The RT group had a higher percentage of pelvic tumors (P = 0.03) and a different distribution of histologies (P = 0.04). Perioperative morbidity was higher in the RT group (44% vs 16% of patients; P = 0.004). After a median follow-up of 39 months, 5-year LRFS was 91% (95% confidence interval, 79%-100%) in the RT group and 65% (57%-74%) in the surgery-only group (P = 0.02). On multivariate analysis, RT was associated with better LRFS (hazard ratio, 0.26; P = 0.03). Five-year disease-specific survival was 93% (95% confidence interval, 82%-100%) in the RT group and 85% (78%-92%) in the surgery-only group (P = 0.3). The addition of advanced-modality RT to surgery for primary retroperitoneal or pelvic sarcoma was associated with improved LRFS, although this did not translate into significantly better disease-specific survival. This treatment strategy warrants further investigation in a randomized trial.
    Annals of Surgery 07/2015; 262(1). DOI:10.1097/SLA.0000000000001063 · 7.19 Impact Factor
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    ABSTRACT: Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.
    Annals of Surgical Oncology 05/2015; DOI:10.1245/s10434-015-4633-x · 3.94 Impact Factor
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    ABSTRACT: En bloc resection for treatment of sacral tumors is the approach of choice for patients with resectable tumors who are well enough to undergo surgery, and studies describe patient survival, postoperative complications, and recurrence rates associated with this treatment. However, most of these studies do not provide patient-reported functional outcomes other than binary metrics for bowel and bladder function postresection. The purpose of this study was to use validated patient-reported outcomes tools to compare quality of life based on level of sacral resection in terms of (1) physical and mental health; (2) pain; (3) mobility; and (4) incontinence and sexual function. Our analysis included 33 patients (19 men, 14 women) who had a mean age of 53 years (range, 22-72 years) with a quality-of-life survey administered at a mean postoperative followup of 41 months (range, 6-123 months). The majority of patient-reported quality-of-life outcome surveys for this study were taken from the National Institute of Health's Patient Reported Outcome Measurement Information System (PROMIS) system. To assess physical and mental health, the PROMIS Global Items Survey with physical and mental subscores, Anxiety, and Depression scores were used. Pain outcomes were assessed using PROMIS Pain Intensity and Pain Interference surveys. Patient-reported lower extremity function was assessed using the PROMIS Mobility Survey. Patient-reported quality of life for sexual function was assessed using the PROMIS Sex Interest and Orgasm survey, whereas incontinence was measured using the International Continence Society Voiding and Incontinence scores and the Modified Obstruction and Defecation Score. Surveys were collected prospectively during clinic visits in the postoperative period. Patients were grouped by the level of osteotomy as determined by review of postoperative MRI or CT and half levels were grouped with the more cephalad level. This resulted in the inclusion of total sacrectomy (N = 6), S1 (N = 8), S2 (N = 10), S3 (N = 5), and S4 (N = 4). One-way analysis of variance tests on means or ranks were used to conduct statistical analysis between levels. Patients with more caudal resections had higher physical health (95% confidence interval [CI] total sacrectomy 36-42 versus S4 50-64, p < 0.001), less intense pain (95% CI total sacrectomy 47-60 versus S4 28-37, p < 0.001), less interference resulting from pain (95% CI total sacrectomy 58-69 versus S4 36-51, p = 0.004), higher mobility (95% CI total sacrectomy 24-46 versus S4 59-59, p = 0.002), and were more functionally able to achieve orgasm (95% CI S1 1-1 versus S4 2.2-5.3, p = 0.043). No difference was found for PROMIS Global Item Mental Health Subscore, Sex Interest, Sex Satisfaction, modified obstruction and defecation score, and International Continence Society Voiding and Incontinence although this could be the result of an inadequate sample size. Our analysis on patient-reported quality of life based on the level of bony resection in patients who underwent resection for primary sacral tumor indicates that patients with higher resections have more pain and loss of physical function in comparison to patients with lower resections. Additionally, use of the PROMIS outcomes allows for comparisons to normative data. Level III, therapeutic study.
    Clinical Orthopaedics and Related Research 05/2015; DOI:10.1007/s11999-015-4361-3 · 2.88 Impact Factor
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    ABSTRACT: To evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among twelve sarcoma radiation oncologists.
    International journal of radiation oncology, biology, physics 05/2015; DOI:10.1016/j.ijrobp.2015.04.039 · 4.18 Impact Factor
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    ABSTRACT: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 GyRBE (50.4-55.8 GyRBE). Tumor size was measured before initial CT and before RT. With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm(3) vs 43 cm(3), P=.9) but a greater median volume before RT (pre-RT) (40 cm(3) vs 7 cm(3), P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 04/2015; 92(2). DOI:10.1016/j.ijrobp.2015.01.049 · 4.18 Impact Factor
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    ABSTRACT: To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm(3) vs 63.4 cm(3); P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 12/2014; 90(5):1030-6. DOI:10.1016/j.ijrobp.2014.08.016 · 4.18 Impact Factor
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    ABSTRACT: Background and Objectives The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and surgery in extremity soft tissue sarcomas (STS) is unclear. We assessed the contribution of a boost to local control (LC), disease-free survival (DFS), and overall survival (OS). Methods We identified 67 patients treated from 1987 to 2011 with pre-operative RT and surgery with positive margin(s). Select patients received a boost delivered as peri-operative Iridium-192 brachytherapy (BRT), intra-operative electrons (IORT), or post-operative external beam RT (EBRT). ResultsTen patients received no RT boost, 10 received a BRT or IORT boost, and 47 received an EBRT boost. Five-year LC rates for no boost, BRT/IORT boost, and EBRT boost were 100%, 78%, and 71% (P=0.5). On multivariate analysis, there were no significant predictors for LC. Variables associated with improved DFS rates were single positive margin (P=0.007) and low tumor grade (P=0.03). Tumor size <5cm (P=0.003), low grade (P=0.001), and boost (P=0.02) were associated with longer survival. Conclusions We did not identify a LC advantage for an RT boost. Given the unidentified selection factors for delivery of boost and its potential toxicities, its role in this setting remains unproven. J. Surg. Oncol. 2014 110:817-822. (c) 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 12/2014; 110(7). DOI:10.1002/jso.23741 · 2.84 Impact Factor
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    ABSTRACT: Local recurrence (LR) following limb-sparing surgery and radiation therapy (RT) for extremity soft tissue sarcoma (STS) is rare. The current study investigates the utility of surveillance nuclear magnetic resonance imaging (MRI) for detection of asymptomatic LRs. The study cohort consisted of 168 adult patients with extremity STS treated with limb-sparing surgery and RT with curative intent between October 2001 and January 2011. Follow-up surveillance MRIs and history and physical examinations were performed per the NCCN guidelines with additional MRIs as clinically indicated. The method of LR detection and MRI number and indication were determined. After a median follow-up of 4.7 years (range: 0.6-10.5) 11 (6.5%; 11/168) patients developed LRs. Five hundred two MRIs were obtained, 429 (85.5%; 429/502) for surveillance and 73 (14.5%; 73/502) as clinically indicated. One hundred fourteen patients underwent ≥1 surveillance MRI. The median surveillance MRI interval was 6.4 months (range 1.4-68.9). Surveillance MRI detected an asymptomatic LR in 1 (0.9%; 1/114) patient with a complex reconstruction. Surveillance MRI infrequently detects asymptomatic LRs following limb-sparing surgery and RT for extremity STS and should be limited to patients whose primary tumor sites are not easily assessed by history and physical examination. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 05/2014; 109(6). DOI:10.1002/jso.23541 · 2.84 Impact Factor
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    ABSTRACT: Mutations in the gene-encoding β-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome. Single-base extension genotyping of the CTNNB1 gene was performed on 145 sporadic, paraffin-embedded desmoid tumor specimens. Correlation of mutation status with outcome was performed on a subset of 115 patients who underwent macroscopically complete surgical resection. CTNNB1 mutations were detected in 106 of 145 (73%) tumor specimens and in 86 of 115 (75%) specimens from patients who underwent curative-intent surgical resection, including discrete mutations in the following codons of CTNNB1 exon 3: T41A (46%), S45F (25%), S45P (1.7%), and S45C (0.9%). Desmoid tumors of the superficial trunk were significantly less likely to harbor CTNNB1 mutations than tumors located elsewhere, but none of the other examined clinicopathologic factors were found to be associated with CTNNB1 mutation status. At a median follow-up of 31 months, 5-year recurrence-free survival was slightly, although not statistically significantly, worse for patients with β-catenin-mutated tumors than for those with wild-type tumors (58% vs. 74%, respectively). The specific CTNNB1 codon mutation did not correlate with the risk for recurrence. CTNNB1 mutations are indeed common in sporadic desmoid tumors. However, our study did not detect a statistically significant difference in recurrence risk according to either the CTNNB1 mutation status or the specific CTNNB1 mutation.
    The Oncologist 08/2013; 18(9). DOI:10.1634/theoncologist.2012-0449 · 4.54 Impact Factor
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    ABSTRACT: To determine the feasibility of surgical placement of biologic mesh spacers to displace bowel and other radiation-sensitive organs prior to external beam radiation for difficult retroperitoneal and pelvic tumors. Tumors were resected if possible, and intraoperative electron radiation therapy (IOERT) was directed to the tumor or tumor bed in selected patients. Biologic mesh spacers comprised of cadaveric human skin treated to remove cells and preserve extracellular matrix (Alloderm; Lifecell, Branchburg, NJ) were then placed around the tumor or tumor bed. External radiation techniques included proton beam radiation therapy (PBRT) and intensity modulated radiation therapy (IMRT). Patients had primary sarcomas (n = 2), radiation-associated sarcomas (n = 1), or isolated metastases (n = 2) in the retroperitoneum or pelvis. One patient received preoperative radiation. Three tumors were marginally resected (R1 resection) while 2 tumors were left in situ, and 3 patients received IOERT (10-17 Gy) to the tumor or tumor bed. Up to 4 sheets of biologic mesh were used as spacers around the tumor or tumor bed to displace small bowel, colon, ureter, bladder, or pancreas. The average distance of the 4 closest organs prior to mesh placement was 1.3-9 mm and after mesh placement was 8.0-23.5 mm. Preoperative or postoperative radiation 36-76 Gy was delivered by IMRT or PBRT. There were no early complications from mesh placement and late complications possibly related to radiation included 1 vertebral body compression fracture and 1 deep vein thrombosis. There were no mesh-related infections and none of the meshes required removal. All 5 patients currently remain free of disease progression after 3-38 months. Biologic mesh spacers can be placed around tumors or tumor beds to displace radiation-sensitive organs and may allow for safer delivery of external beam radiation.
    07/2013; 3(3):199-208. DOI:10.1016/j.prro.2012.06.008
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    ABSTRACT: Study Design: A retrospective review.Objective: The purpose of this study is to report the results of high dose proton based definitive radiotherapy for unresected spinal chordomas.Summary of Background Data: Spine chordoma is treated primarily by surgical resection. However, local recurrence rate is high. Adjuvant radiotherapy improves local control. In certain locations, such as high sacrum, resection may result in significant neurological dysfunction.METHODS: We retrospectively reviewed 24 patients with newly diagnosed, previously untreated spinal chordomas (core biopsy only; no prior incision or resection) treated with high dose definitive radiotherapy alone using protons and photons at our center from 1988 to 2009.RESULTS: Reasons for radiotherapy alone included medical inoperability (3) and concern for neurological dysfunction based on spine level (21). Median age was 69.5 years. Tumor locations included cervical (2), thoracic (1), lumbar (2), S1/2 (17), and S3-below (2). Median maximal tumor diameter was 6.6 cm (1.4-25.5), and median tumor volume was 198.3 cc (4.65-2061). Median total dose was 77.4 GyRBE. Analysis at median follow up of 56 months showed overall survival of 91.7% and 78.1%, chordoma specific survival of 95.7% and 81.5%, local progression free survival of 90.4% and 79.8% and metastases free survival of 86.5% and 76.3%, at 3 and 5 years respectively. Tumor volume >500 cc was correlated with worse overall survival. Long-term side effects included 8 sacral insufficiency fractures (none required surgical stabilization), 1 secondary malignancy, 1 foot drop, 1 erectile dysfunction, 1 perineal numbness, 2 worsening urinary/fecal incontinence, and 4 grade-2 rectal bleeding. None required new colostomy. All surviving patients remained ambulatory.CONCLUSION: These results support the use of high dose definitive radiotherapy for patients with medically inoperable or otherwise unresected, mobile spine or sacrococcygeal chordomas.
    Spine 04/2013; DOI:10.1097/BRS.0b013e318296e7d7 · 2.45 Impact Factor
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    ABSTRACT: Background and Objectives. Atypical lipomas are uncommon, slow-growing benign tumors. While surgery has been the primary treatment modality, we have managed some patients with radiation (RT) as a component of the treatment and have reported their outcomes in this study. Methods. A retrospective review of all cases of extremity and trunk atypical lipomas in The Sarcoma Database at the study institution was conducted. Results. Thirteen patients were identified. All patients underwent surgical resection at initial presentation and received pre- or postoperative radiation for subtotal resection (n = 2), local recurrence (n = 8), or progressive disease (n = 3). The median total radiation dose was 50 Gy. Median followup was 65.1 months. All patients treated with RT remained free of disease at the last followup. No grade 3 or higher late toxicity from radiation was observed. No cases of tumor dedifferentiation occurred. Conclusion. For recurrent or residual atypical lipomas, a combination of reexcision and RT can provide long-term local control with acceptable morbidity. For recurrent tumors, pre-op RT of 50 Gy appears to be an effective and well-tolerated management approach.
    Sarcoma 01/2013; 2013:485483. DOI:10.1155/2013/485483
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    ABSTRACT: BACKGROUND: Patients with large, high-grade extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of pre-operative chemotherapy consisting of mesna, adriamycin, ifosfamide and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and post-operative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this study is to assess outcomes in a recent cohort of patients treated on this regimen. METHODS: We retrospectively reviewed records of 66 consecutive patients with STS of the extremity or trunk who were treated with the aforementioned regimen from May 2000 to April 2011. Clinicopathologic characteristics and patient outcomes were analysed. RESULTS: Sixty-six patients were analysed and were equally divided between grade 2 and 3 tumours. Margins were negative in 57 (89%) patients and positive in seven (11%) patients. At a median follow-up of 46months, there were six (9%) locoregional and 20 (30%) distant recurrences. The locoregional and distant 5-year recurrence-free survival (RFS) rates were 91% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. Thirty-four (52%) patients had grade 3 or 4 acute haematologic chemotherapy-related toxicity. There were no statistically significant predictors of OS or RFS. CONCLUSIONS: For a contemporary cohort of patients with high-risk extremity and truncal STS, a regimen of neoadjuvant chemoradiotherapy and surgery continues to result in high rates of survival with tolerable short- and long-term toxicity.
    European journal of cancer (Oxford, England: 1990) 10/2012; 49(4). DOI:10.1016/j.ejca.2012.10.002 · 4.82 Impact Factor
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    ABSTRACT: BACKGROUND: Desmoid tumors are rare and exhibit a highly unpredictable natural history. We sought to analyze prognostic factors associated with recurrence in a large single-institution study of patients with desmoid tumors. METHODS: We performed a retrospective review of 177 patients with desmoid tumor who underwent macroscopically complete surgical resection, with or without the addition of radiotherapy (RT) or systemic therapy, from 1970 to 2009. We examined patterns of presentation, all known risk factors for recurrence, and their association with recurrence-free survival (RFS). RESULTS: Twenty-two patients (12 %) had intra-abdominal desmoid tumors, and 155 (88 %) had extra-abdominal tumors. Patterns of presentation included primary (n = 133, 75 %) and locally recurrent (n = 44, 25 %) disease. Treatment was surgery alone in 125 patients (71 %), surgery and RT in 36 (20 %), and surgery and systemic therapy with or without RT in 20 (11 %). Median follow-up was 40 months. Overall, the local relapse rate was 29 %, and 10-year RFS was 60 %. R0 resection status was the only predictor of freedom from local recurrence on multivariate analysis (odds ratio 0.32; 95 % confidence interval 0.15-0.66; P = 0.002). The selective use of adjuvant RT appeared to improve local control in patients with positive margins. CONCLUSIONS: For patients with desmoid tumors undergoing surgery, wide excision with negative margins should be the goal, but not at the expense of function, as fewer than half of patients with positive margins will experience recurrence.
    Annals of Surgical Oncology 09/2012; DOI:10.1245/s10434-012-2638-2 · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND: Myxofibrosarcomas (MFS) are a historically heterogeneous group of tumors that exhibit a propensity for local recurrence. The objectives of this study were to analyze the prognostic factors and outcomes of patients with MFS treated at a single institution. METHODS: We retrospectively reviewed the records of 69 consecutive patients with pathologically confirmed MFS of the extremities or superficial trunk who underwent surgery from August 1995 to November 2010. Clinicopathologic features, treatments, and patient outcomes were reviewed. RESULTS: Sixty-nine patients were identified, of whom 38 were men (55 %). The median age was 62 years. Sixty-four patients (93 %) presented with primary tumors, and 5 patients (7 %) presented with locally recurrent tumors. Median tumor size was 6.0 cm, and 44 patients (64 %) had grade 3 tumors (FNCLCC [Fédération Nationale des Centres de Lutte Contre le Cancer] classification). Margins were microscopically positive in 14 patients (20 %) and negative in 55 patients (80 %), including close margins (<1 mm) in 14 patients (20 %). Fifty-three patients (77 %) received radiotherapy. At a median follow-up of 41 months, there were 11 local (16 %) and 11 distant (16 %) recurrences. The local and distant 5-year recurrence-free survival rates were 72 % and 82 %, and the 5-year overall survival was 61 %. Increased age (scaled by 0.1; hazard ratio [HR] 1.80, P = 0.002) and tumor size (HR 1.12, P = 0.004) were negatively correlated with overall survival. Positive/close (<1 mm) margin status (HR 4.34, P = 0.030) predicted worsened local recurrence-free survival. CONCLUSIONS: MFS exhibit a propensity for local recurrence, which is predicted by resection with positive or close margins. Aggressive surgery combined with radiotherapy may contribute to more effective local control.
    Annals of Surgical Oncology 08/2012; DOI:10.1245/s10434-012-2572-3 · 3.94 Impact Factor
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    ABSTRACT: Patients with large, high-grade, extremity soft tissue sarcomas (STS) are at significant risk for distant recurrence and death. A regimen of preoperative chemotherapy consisting of mesna, Adriamycin (doxorubicin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT) and followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. We report the long-term follow-up data on 48 patients treated with this regimen compared to an historical matched-control patient population. Adult patients with high-grade extremity STS ≥ 8 cm were treated with 3 cycles of preoperative chemotherapy combined with 44 Gy of RT followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy of RT was delivered postoperatively. Patients received the MAID/RT regimen from 1989 through 1999. After a median follow-up of 9.3 years in surviving patients in the MAID group and 13.2 years in surviving patients in the control group, the 7-year disease-specific and overall survival rates were 81% and 50% (P = .004) and 79% and 45% (P = .003) for the MAID and control patients, respectively. Five of 11 patients in the MAID group and 7 of 25 control patients died of sarcoma ≥5 years after treatment. One patient in the MAID group developed a fatal myelodysplasia at 53 months. For patients with high-risk, extremity STS, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery are sustained even with long-term follow-up.
    Cancer 08/2012; 118(15):3758-65. DOI:10.1002/cncr.26696 · 4.90 Impact Factor
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    ABSTRACT: To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS). This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival. Data from 18 patients (78 % male) were reviewed. Sixteen patients (89 %) had AS originating in the right atrium. At diagnosis, eight patients (44 %) had localized/locally advanced disease and ten patients (56 %) had metastatic disease. Initial treatment strategies included resection (44 %), chemotherapy (39 %), and radiotherapy (11 %). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12 months. Median overall survival (OS) was 13 months for the entire cohort; median OS was 19.5 months for those presenting with localized/locally advanced AS and 6 months for those with metastatic disease at presentation (p = 0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5 months, p = 0.01). Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression.
    Annals of Surgical Oncology 04/2012; 19(8):2707-15. DOI:10.1245/s10434-012-2334-2 · 3.94 Impact Factor
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    ABSTRACT: Radiation therapy uses high-energy ionizing radiation beams to treat malignant cancers as well as a variety of benign tumors and medical conditions. James Ewing was the first to report the successful use of radiotherapy in the management of unresectable desmoid tumors in 1928 [1]. Since then several studies have shown excellent control rates with radiation, which indicate a role for radiotherapy in the multidisciplinary management of these nonmalignant tumors [2–6]. Currently, radiation can be used as the primary treatment for desmoids, as an adjunct to surgery, and as the treatment of recurrent disease. Surgery has generally been the standard initial modality for treating patients with desmoid tumors, although experience is accumulating with a more conservative approach of initial observation, deferring surgery or other treatment until there is evidence of progression [7, 8]. Optimizing local control is the key element for the curative treatment of these benign tumors, given their inability to metastasize and the expectation of long-term survival for most patients. This underlies the rationale for combining surgical resection and radiotherapy with the goal of improving local control and to limit the morbidity associated with recurrence in some patients. Despite the large number of published series examining the effect of adding radiation to surgery, there is a lack of consensus on the indications for such an approach. Furthermore, due to the low incidence of desmoids, there are no randomized controlled trials comparing the effect of different treatment modalities in the management of desmoid tumors. In the absence of such high-level evidence, the application of radiation in the management of desmoids is based upon effectiveness seen in retrospective and phase II studies. In most of these studies, radiation has been used largely in patients who have recurred after initial surgery and as primary treatment in those patients who are medically inoperable or those in whom resection presents unacceptable morbidity [9–12]. However, because there are other treatment modalities available for the management of desmoids, the use of radiotherapy must be considered carefully in light of the potential long-term side effects of radiotherapy including the risk of secondary malignancy, particularly in younger patients. Table8.1 outlines the principles of irradiating nonmalignant diseases, which applies to the use of radiation in this disease [13]. Ultimately, treatment decisions are individualized to each patient depending on a range of patient and tumor characteristics [8, 14]. In Fig.8.1, we outline a treatment algorithm that we have found useful in managing patients with desmoid tumors. In this chapter, we discuss separately the role of radiation in the treatment of primary and recurrent desmoid tumors. We will also review the basics of radiation treatment planning and the different radiation techniques that can be applied. KeywordsPrimary radiation therapy for unresected desmoid-Radiation therapy for recurrent desmoid-Adjuvant (postoperative) radiation therapy-Neoadjuvant (preoperative) radiation therapy-Radiotherapy dose-Radiotherapy for pediatric desmoid-Radiotherapy treatment planning-Brachytherapy-Intraoperative radiotherapy-Radiation therapy toxicity-Follow-up guidelines after radiation therapy-Margin status
    12/2011: pages 105-125;
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    ABSTRACT: A study was undertaken to assess clinical outcome and the role of proton therapy for local control of osteosarcoma (OSA). All patients who received proton therapy or mixed photon-proton radiotherapy from 1983 to 2009 at the Massachusetts General Hospital were reviewed. Criteria for proton therapy were the need for high dose in the context of highly conformal radiotherapy of unresected or partially resected OSA, positive postoperative margins, postoperative imaging studies with macroscopic disease, or incomplete resection as defined by the surgeon. The primary endpoint was local control of the site treated; secondary endpoints were disease-free survival (DFS), overall survival (OS), long-term toxicity, and prognostic factors associated with clinical outcome. Fifty-five patients with a median age of 29 years (range, 2-76 years) were offered proton therapy. The mean dose was 68.4 gray (Gy; standard deviation, 5.4 Gy). Of the total dose, 58.2% (range, 11%-100%) was delivered with protons. Local control after 3 and 5 years was 82% and 72%, respectively. The distant failure rate was 26% after 3 and 5 years. The 5-year DFS was 65%, and the 5-year OS was 67%. The extent of surgical resection did not correlate with outcome. Risk factors for local failure were ≥ 2 grade disease (P < .0001) and total treatment length (P = .008). Grade 3 to 4 late toxicity was seen in 30.1 % of patients. One patient died from treatment-associated acute lymphocytic leukemia, and 1 from secondary carcinoma of the maxilla. Proton therapy to deliver high radiotherapy doses allows locally curative treatment for some patients with unresectable or incompletely resected OSA.
    Cancer 10/2011; 117(19):4522-30. DOI:10.1002/cncr.26037 · 4.90 Impact Factor
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    ABSTRACT: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Patients with ≥5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.
    International journal of radiation oncology, biology, physics 10/2010; 81(4):1081-90. DOI:10.1016/j.ijrobp.2010.07.024 · 4.18 Impact Factor

Publication Stats

319 Citations
87.01 Total Impact Points

Institutions

  • 2012–2015
    • Harvard Medical School
      • Department of Radiation Oncology
      Boston, Massachusetts, United States
  • 2009–2015
    • Massachusetts General Hospital
      • Department of Radiation Oncology
      Boston, Massachusetts, United States
  • 2010–2013
    • Harvard University
      Cambridge, Massachusetts, United States