Publications by authors named "Thomas Delaney"

192 Publications

Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline.

Pract Radiat Oncol 2021 Jul 19. Epub 2021 Jul 19.

Department of Radiation Oncology, UT-MD Anderson Cancer Center, Houston, Texas.

Purpose: This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults.

Methods: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.

Results: Multidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended.

Conclusions: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life.
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http://dx.doi.org/10.1016/j.prro.2021.04.005DOI Listing
July 2021

Careful with the Cauda.

Authors:
Thomas F DeLaney

Int J Radiat Oncol Biol Phys 2021 Aug;110(5):1265

Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts; Francis H. Burr Proton Therapy Center, Massachusetts General Hospital, Boston, Massachusetts; Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.ijrobp.2018.12.033DOI Listing
August 2021

Role of Radiation Therapy for Newly Diagnosed Retroperitoneal Sarcoma.

Curr Treat Options Oncol 2021 Jul 2;22(9):75. Epub 2021 Jul 2.

Harvard Medical School, Boston, MA, USA.

Opinion Statement: Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.
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http://dx.doi.org/10.1007/s11864-021-00877-6DOI Listing
July 2021

A Rare Australian Case of Cutaneous Cladophialophora bantiana and Review of the Literature.

Acta Derm Venereol 2021 Jul 7;101(7):adv00493. Epub 2021 Jul 7.

Department of Dermatology, Royal Perth Hospital, GPO Box X2213, Perth WA 6847, Australia. E-mail:

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http://dx.doi.org/10.2340/00015555-3860DOI Listing
July 2021

Temporizing Wound VAC Dressing Until Final Negative Margins are Achieved Reduces Myxofibrosarcoma Local Recurrence.

Ann Surg Oncol 2021 Jun 18. Epub 2021 Jun 18.

Orthopaedic Oncology Service, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA, USA.

Background: The microinvasive nature of suprafascial myxofibrosarcoma reduces the accuracy of intraoperative margin assessment, and tumor bed resections after soft-tissue reconstruction are unreliable. In 2017, we began temporizing the excised tumor bed with a wound VAC, delaying soft-tissue coverage until final negative margins were achieved. We compare the oncologic/surgical outcomes of suprafascial myxofibrosarcomas managed with VAC temporization (VT) with single-stage excision/reconstruction (SS).

Methods: We retrospectively studied suprafascial myxofibrosarcomas managed from January 1, 2000 to January 1, 2019 for patients who received neoadjuvant or adjuvant radiation and had at least 2 years of oncologic follow-up at a tertiary referral cancer center. Our primary outcome was local recurrence. Comparisons were performed by using Fisher's exact test or Student's t test. A p value < 0.05 was considered significant.

Results: Fifty-three patients (18 VAC temporized, 35 single stage) were included. While VT patients were older (74.9 ± 10.2 vs. 63.9 ± 13.6, p = 0.003), treatment groups did not significantly differ with respect to comorbidity, tumor volume, stage and grade. VT patients had significantly fewer local recurrences (5.6% vs. 28.6% after SS, p = 0.048) and R1 resections that required an unplanned readmission for tumor bed reexcision (0% vs. 37.1% after SS, p = 0.002). VT required more total surgeries (2.8 ± 0.9 vs. 1.8 ± 0.9 for SS, p = 0.0002). Postoperative infectious and wound complications were equivalent.

Conclusions: Our VAC temporization strategy had a significantly lower LR than SS treatment. While high quality multi-institutional validation is required, VT may represent a paradigm shift in the management of myxofibrosarcoma.
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http://dx.doi.org/10.1245/s10434-021-10242-4DOI Listing
June 2021

Cutaneous involvement by multiple myeloma presenting as erythematous indurated plaques at the site of cardiac pacemaker insertion.

JAAD Case Rep 2021 Jun 24;12:54-57. Epub 2021 Apr 24.

Dermatology Department, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.

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http://dx.doi.org/10.1016/j.jdcr.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134960PMC
June 2021

Low-dose preoperative radiation, resection, and reduced-field postoperative radiation for soft tissue sarcomas.

J Surg Oncol 2021 Sep 18;124(3):400-410. Epub 2021 Apr 18.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background And Objectives: Radiotherapy (RT) enables conservative surgery for soft tissue sarcoma (STS). RT can be delivered either pre-operatively (PreRT) or postoperatively (PORT), yet in some patients, neither approach is fully satisfactory (e.g., urgent surgery or wound healing risk prevents PreRT, yet PORT alone cannot cover the entire surgical field). We hypothesized that, in such situations, low-dose PreRT (LD-PreRT) would decrease the risk of intraoperative tumor seeding and thus permit PORT to a reduced volume (covering the high-risk tumor bed but not all surgically manipulated tissues).

Methods: We identified a single-institution retrospective cohort of 78 patients treated with LD-PreRT (10-30 Gy), resection, and PORT between 1980 and 2018.

Results: At a median follow-up of 8.2 years, 8-year overall survival (OS) was 65.9%, disease-free survival (DFS) 50.5%, and local control (LC) 76.7%; in 45 patients with extremity/superficial trunk (E/ST) STS, 8-year LC was 80.9%. Both before and after propensity score adjustment, there were no differences in OS, DFS, or LC between this cohort and a separate cohort of 394 STS (221 E/ST-STS) patients treated with surgery and PORT alone.

Conclusions: In patients for whom neither PreRT nor PORT alone is optimal, LD-PreRT may prevent intraoperative tumor seeding and enable PORT to a reduced volume while preserving oncologic outcomes.
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http://dx.doi.org/10.1002/jso.26503DOI Listing
September 2021

Management of Primary Retroperitoneal Sarcoma (RPS) in the Adult: An Updated Consensus Approach from the Transatlantic Australasian RPS Working Group.

Ann Surg Oncol 2021 Apr 14. Epub 2021 Apr 14.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document.

Methods: The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation.

Results: Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies.

Conclusions: Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.
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http://dx.doi.org/10.1245/s10434-021-09654-zDOI Listing
April 2021

The Reality of Randomized Controlled Trials for Assessing the Benefit of Proton Therapy: Critically Examining the Intent-to-Treat Principle in the Presence of Insurance Denial.

Adv Radiat Oncol 2021 Mar-Apr;6(2):100635. Epub 2020 Dec 2.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: This study hypothesized that insurance denial would lead to bias and loss of statistical power when evaluating the results from an intent-to-treat (ITT), per-protocol, and as-treated analyses using a simulated randomized clinical trial comparing proton therapy to intensity modulated radiation therapy where patients incurred increasing rates of insurance denial.

Methods And Materials: Simulations used a binary endpoint to assess differences between treatment arms after applying ITT, per-protocol, and as-treated analyses. Two scenarios were developed: 1 with clinical success independent of age and another assuming dependence on age. Insurance denial was assumed possible for patients <65 years. All scenarios considered an age distribution with mean ± standard deviation: 55 ± 15 years, rates of insurance denial ranging from 0%-40%, and a sample of N = 300 patients (150 per arm). Clinical success rates were defined as 70% for proton therapy and 50% for intensity modulated radiation therapy. The average treatment effect, bias, and power were compared after applying 5000 simulations.

Results: Increasing rates of insurance denial demonstrated inherent weaknesses among all 3 analytical approaches. With clinical success independent of age, a per-protocol analysis demonstrated the least bias and loss of power. When clinical success was dependent on age, the per-protocol and ITT analyses resulted in a similar trend with respect to bias and loss of power, with both outperforming the as-treated analysis.

Conclusions: Insurance denial leads to misclassification bias in the ITT analysis, a missing data problem in the per-protocol analysis, and covariate imbalance between treatment arms in the as-treated analysis. Moreover, insurance denial forces the critical appraisal of patient features (eg, age) affected by the denial and potentially influencing clinical success. In the presence of insurance denial, our study suggests cautious reporting of ITT and as-treated analyses, and placing primary emphasis on the results of the per-protocol analysis.
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http://dx.doi.org/10.1016/j.adro.2020.100635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940795PMC
December 2020

A Peer-Based Strategy to Overcome HPV Vaccination Inequities in Rural Communities: A Physical Distancing-Compliant Approach.

Crit Rev Eukaryot Gene Expr 2021 ;31(1):61-69

KM Consulting, New Jersey, USA.

The human papilloma virus (HPV) vaccine is the world's first proven and effective vaccine to prevent cancers in males and females when administered pre-exposure. Like most of the US, barely half of Vermont teens are up-to-date with the vaccination, with comparable deficits in New Hampshire and Maine. The rates for HPV vaccine initiation and completion are as low as 33% in rural New England. Consequently, there is a compelling responsibility to communicate its importance to unvaccinated teenagers before their risk for infection increases. Messaging in rural areas promoting HPV vaccination is compromised by community-based characteristics that include access to appropriate medical care, poor media coverage, parental and peer influence, and skepticism of science and medicine. Current strategies are predominantly passive access to literature and Internet-based information. Evidence indicates that performance-based messaging can clarify the importance of HPV vaccination to teenagers and their parents in rural areas. Increased HPV vaccination will significantly contribute to the prevention of a broadening spectrum of cancers. Reducing rurality-based inequities is a public health priority. Development of a performance-based peer-communication intervention can capture a window of opportunity to provide increasingly effective and sustained HPV protection. An effective approach can be partnering rural schools and regional health teams with a program that is nimble and scalable to respond to public health policies and practices compliant with COVID-19 pandemic-related modifications on physical distancing and interacting in the foreseeable future.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021036945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128079PMC
March 2021

Preoperative radiotherapy for retroperitoneal sarcoma.

Lancet Oncol 2021 01;22(1):e1

Basic and Translational Research Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.

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http://dx.doi.org/10.1016/S1470-2045(20)30632-XDOI Listing
January 2021

What Is the Role of Neoadjuvant Radiation Therapy for Retroperitoneal Sarcoma?

Adv Surg 2020 09 20;54:273-284. Epub 2020 Jun 20.

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, YAW-7-7926, Boston, MA 02114, USA. Electronic address:

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http://dx.doi.org/10.1016/j.yasu.2020.05.003DOI Listing
September 2020

Novel Body Composition Predictors of Outcome in Patients With Angiosarcoma of the Breast: A Preliminary Study.

J Comput Assist Tomogr 2020 Jul/Aug;44(4):605-609

From the Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Objective: The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients.

Materials: Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emission tomography/CT were identified. A control group was selected (n = 25). Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were assessed on unenhanced computed tomographies. Breast adipose tissue (BAT) volumes of the uninvolved breast were quantified. Metabolic activity of VAT, SAT, and BAT was calculated (standardized uptake value [SUV]).

Results: Breast angiosarcoma patients had higher metabolic activity of VAT compared with controls (SUV 0.93 ± 0.39 vs 0.64 ± 0.11, P = 0.044). Within the patient group, there were 6 deaths (46.2%). Patients who died had higher SAT activity (SUV 0.52 ± 0.24 vs 0.29 ± 0.06, P = 0.027) and higher BAT metabolic activity (SUV 0.48 ± 0.20 vs 0.27 ± 0.11, P = 0.045) compared with nondeceased patients.

Conclusions: Patients with breast angiosarcoma have higher metabolic activity of VAT. Higher abdominal SAT and higher BAT metabolic activity of the uninvolved breast might predict mortality.
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http://dx.doi.org/10.1097/RCT.0000000000001066DOI Listing
July 2020

Multi-institutional analysis of stereotactic body radiotherapy for sarcoma pulmonary metastases: High rates of local control with favorable toxicity.

J Surg Oncol 2020 Oct 25;122(5):877-883. Epub 2020 Jun 25.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Background/objectives: Oligometastatic sarcoma pulmonary metastases (PM's) are traditionally treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) is an effective, safe alternative to surgery that can achieve excellent local control (LC) with a favorable toxicity profile.

Methods: Patients treated with SBRT for sarcoma PM's from 2011 to 2016 at Massachusetts General Hospital and the University of Pennsylvania were included. Median dose was 50 Gy. Patients underwent computed tomography (CT) or positron emission tomography/CT Q3 months post-SBRT.

Results: 44 patients with 56 separate PM's were treated with SBRT. Median age was 59 (range 19-82). 82% received prior chemotherapy, 66% had prior pulmonary resections (range, 1-5 resections), and 32% received prior thoracic radiotherapy. Median lesion size was 2.0 cm (range, 0.5-8.1 cm). Median follow-up was 16 months and 25 months for patients alive at last follow-up. Overall survival at 12 and 24 months was 74% (95% confidence interval [CI], 67%-81%) and 46% (95% CI, 38%-55%). LC at 12 and 24 months was 96% (95% CI, 93%-98%) and 90% (95% CI, 84%-96%). LC and overall survival did not differ based on age, gender, histology, fractionation, lesion location, or size (P > .05). Three developed Common Terminology Criteria for Adverse Events version 4 grade-2 chest-wall toxicities; one had grade-2 pneumonitis.

Conclusions: In the first multi-institutional series on SBRT for sarcoma PM's, SBRT has excellent LC and is well-tolerated. SBRT should be considered as an alternative/complement to resection.
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http://dx.doi.org/10.1002/jso.26078DOI Listing
October 2020

Assessing second cancer risk after primary cancer treatment with photon or proton radiotherapy.

Cancer 2020 08 19;126(15):3397-3399. Epub 2020 May 19.

Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1002/cncr.32936DOI Listing
August 2020

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) with painful erythematous nodules.

BMJ Case Rep 2020 Apr 22;13(4). Epub 2020 Apr 22.

Dermatology Department, Royal Perth Hospital, Perth, Western Australia, Australia.

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) is an uncommon syndrome characterised by acute onset severe synovitis of the radiocarpal and small joints of the hands, with associated pitting edema. Discussed here is the case of a 69-year-old man who presented to the emergency department of a tertiary hospital with acute bilateral hand swelling. This was on a background of a recent diagnosis of metastatic adenocarcinoma of the caecum and subsequent hemicolectomy. There was a history of general malaise, fever and lethargy for 5 days prior to the swelling of the hands. On examination, the upper limbs were swollen to the elbow bilaterally. Painful erythematous nodules were noted on the dorsal and palmar aspects of the hands and violaceous periungual discolouration was observed on the right fourth and fifth fingers. Prednisolone was commenced resulting in a dramatic resolution of the articular and cutaneous manifestations within 3 weeks.
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http://dx.doi.org/10.1136/bcr-2019-234197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202784PMC
April 2020

Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer.

J Clin Oncol 2020 05 11;38(14):1569-1579. Epub 2020 Mar 11.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer.

Methods: This phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up).

Results: This trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial's stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% 51.2%) and 3-year overall survival rates (44.5% 44.5%) were similar.

Conclusion: For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.
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http://dx.doi.org/10.1200/JCO.19.02503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213588PMC
May 2020

Radiation Strategies for Spine Chordoma: Proton Beam, Carbon Ions, and Stereotactic Body Radiation Therapy.

Neurosurg Clin N Am 2020 Apr;31(2):263-288

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address:

Surgery alone provides suboptimal local control of spine and sacral chordomas. Radiotherapy (RT) may improve local control in patients undergoing surgery and be used as definitive-intent treatment in patients not undergoing surgery. Although conventional-dose RT is inadequate for these radioresistant tumors, newer techniques allow treatment of the tumor to higher, more effective doses while limiting spinal cord dose to safe levels. The best local control is achieved when RT is delivered in the primary setting; RT dose is a critical determinant of local control. RT should be considered for all spine and sacral chordoma patients.
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http://dx.doi.org/10.1016/j.nec.2019.12.002DOI Listing
April 2020

ACR-ASTRO Practice Parameter for the Performance of Proton Beam Radiation Therapy.

Am J Clin Oncol 2020 03;43(3):149-159

Dartmouth-Hitchcock Medical Center, Lebanon, NH.

Aim/objectives/background: The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for proton beam radiation therapy. Proton radiotherapy is the application of a high-energy proton beam to a patient in a clinical setting with therapeutic intent. Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and greater dose to target tumor tissues.

Methods: A literature search was performed to identify published articles regarding clinical outcomes, reviews, quality assurance methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text. The following recommendations are based on firsthand experiences of multiple clinical authorities who employ proton therapy and have been peer reviewed by experts at different practicing institutions.

Results: This practice parameter is developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance standards, indications, and suggested documentation.

Conclusions: This practice parameter is a tool to guide technical use of proton therapy and does not assess the relative clinical indication of proton radiotherapy when compared with other forms of radiotherapy, but to focus on the best practices required to deliver proton therapy safely and effectively, when clinically indicated. Costs of proton treatments are high, and the economic costs of proton radiotherapy may also need to be considered.
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http://dx.doi.org/10.1097/COC.0000000000000672DOI Listing
March 2020

Prognostic Factors in Dedifferentiated Chondrosarcoma: A Retrospective Analysis of a Large Series Treated at a Single Institution.

Sarcoma 2019 13;2019:9069272. Epub 2019 Dec 13.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.

Background: Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management.

Methods: In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors.

Results: Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis.

Conclusions: The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients.
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http://dx.doi.org/10.1155/2019/9069272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930709PMC
December 2019

Bone Sarcomas and Desmoids.

Hematol Oncol Clin North Am 2020 02 28;34(1):177-188. Epub 2019 Oct 28.

Department of Radiation Oncology, Harvard Medical School, Francis H. Burr Proton Therapy Center, Massachusetts General Hospital, 30 Fruit Street, Boston, MA 02114, USA. Electronic address:

Bone sarcomas are rare tumors arising in bone, representing only a small fraction of solid malignant tumors. Desmoids are benign, infiltrative soft tissue neoplasms. Because of their scarcity and a paucity of data, the management of these tumors can be challenging, especially for clinicians who infrequently encounter these tumors. This article reviews the current literature regarding the diagnosis, work-up, and treatment of these uncommon mesenchymal tumors.
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http://dx.doi.org/10.1016/j.hoc.2019.09.002DOI Listing
February 2020

Malignant Soft-Tissue Sarcomas.

Hematol Oncol Clin North Am 2020 02 28;34(1):161-175. Epub 2019 Oct 28.

Department of Radiation Oncology, Francis H. Burr Proton Beam Therapy Center, Massachusetts General Hospital, Harvard Medical School, 30 Fruit Street, Boston, MA 02114, USA. Electronic address:

Soft-tissue sarcomas are cancerous growths of mesenchymal tissues, most commonly arising from fat, muscles, and other connective tissues. Sarcomas are rare, representing only a small fraction of solid malignant tumors. Because of their scarcity and a relative paucity of data, the management of sarcomas can be challenging, especially for those who infrequently encounter these tumors. Herein, the authors review the current literature regarding the diagnosis, workup, and treatment of adult soft-tissue sarcomas.
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http://dx.doi.org/10.1016/j.hoc.2019.08.022DOI Listing
February 2020

The Role of the Dental Community in Oropharyngeal Cancer Prevention Through HPV Vaccine Advocacy.

J Cancer Educ 2021 Apr;36(2):299-304

Robert Larner, MD College of Medicine, University of Vermont, 89 Beaumont Ave, Burlington, VT, 05405, USA.

As rates of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) continue to rise, the dental community's role in primary prevention efforts related to HPV vaccination will become increasingly important. The aim of this study was to assess knowledge, beliefs, practices, and perceived barriers regarding HPV and HPV vaccine advocacy within the dental community. A sample of 266 dentists and dental hygienists completed an online survey, and responses were then analyzed using frequencies of responses, t tests, chi-square tests, and Spearman's correlations. Ninety percent of providers believe it is important to play an "active role" in their patients' general medical care, yet only 50% believe it is their responsibility to recommend the HPV vaccine. Only 50% feel knowledgeable enough to recommend the vaccine. 78.6% of providers rarely discuss HPV vaccination with their age-appropriate patients, and 82% rarely recommend the vaccine. The two most strongly agreed-upon barriers were "parent concerns about the safety or efficacy of the vaccine" (71.6%) and "parent opposition to HPV vaccination for philosophical or religious reasons" (72.6%). Dentists were more knowledgeable about HPV vaccination and more likely to recommend the vaccine than hygienists. Higher levels of HPV-related knowledge correlated positively with beliefs and practices that support HPV vaccine advocacy. We have identified multiple opportunities for intervention aimed at increasing vaccine advocacy among oral health providers. These include clarification of role from dental professional organizations, alleviation of concerns related to perceived parental objection to the vaccine, and educational interventions targeting knowledge deficits among oral health providers.
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http://dx.doi.org/10.1007/s13187-019-01628-wDOI Listing
April 2021

Physical Function and Quality of Life After Resection of Mobile Spine Chondrosarcoma.

Global Spine J 2019 Oct 18;9(7):743-753. Epub 2019 Feb 18.

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Study Design: Retrospective cohort study.

Objectives: (1) To assess patient-reported outcomes-physical function, pain, and quality of life-in patients who underwent resection of a mobile spine chondrosarcoma. (2) To assess complications (90 days), readmissions, reoperations, oncological outcomes, and neurologic status.

Methods: Thirty-three patients with spinal conventional chondrosarcoma resection between 1984 and 2014 at one hospital were included. The primary outcome measures were-minimally 6 months after surgery-the EuroQol 5 Dimensions (EQ5D), PROMIS-Physical Function, PROMIS-Pain Intensity, and Oswestry (ODI) Disability Index, or Neck (NDI) Disability established in 14 out of 20 alive (70.0%) patients. Complications, readmission, reoperations, oncological outcomes, and neurological status were reported for the complete cohort of 33 patients.

Results: After spine chondrosarcoma resection, patients (n = 14) reported worse physical function (median 43, range 22-61, = .026), worse quality of life (median EQ5D 0.70, range 0.04-1, = .022), and comparable pain intensity (median 47, range 31-56, = .362) when compared with US general population values. The median NDI/ODI was 25 (range 0-72) indicating mild to moderate disability. Patients undergoing reoperation had worse patient-reported outcomes than those who did not. Eighteen (55.5%) out of 33 patients suffered complications (90 days), 14 (42.4%) had unplanned readmission, and 13 (39.4%) underwent reoperation. Intralesional resection was associated with increased readmission, reoperation, and recurrence rate.

Conclusions: Chondrosarcoma affects quality of life and physical function and its treatment frequently results in complications and reoperations. Our findings can be used to inform future patients about expected outcomes.
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http://dx.doi.org/10.1177/2192568219830330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745645PMC
October 2019

Clinical and Molecular Analysis of Pathologic Fracture-associated Osteosarcoma: MicroRNA profile Is Different and Correlates with Prognosis.

Clin Orthop Relat Res 2019 Sep;477(9):2114-2126

S. A. Lozano Calderón, J. Kim, K. Raskin, J. Schwab, D. Spentzos, Department of Orthopaedic Surgery, Musculoskeletal Oncology Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA Y.-L. Chen, K. Bernstein, T. Delaney, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA I. Chebib, G. P. Nielsen, V. Deshpande, Department of Pathology, Bone and Soft Tissue Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA R. Rubio, Y. E. Wang, J. Quackenbush, Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA R. Rubio, Y. E. Wang, J. Quackenbush, Department of Biostatistics, Harvard School of Public Health, Boston, MA C. Garbutt, C. E. Lietz, G. Cote, Department of Medical Oncology, Massachusetts General Hospital, Boston, MA; Department of Medical Oncology, Massachusetts General Hospital, Boston, MA.

Background: MicroRNAs are small, noncoding RNAs that regulate the expression of posttranslational genes. The presence of some specific microRNAs has been associated with increased risk of both local recurrence and metastasis and worse survival in patients with osteosarcoma. Pathologic fractures in osteosarcoma are considered to be more the manifestation of a neoplasm with a more aggressive biological behavior than the cause itself of worse prognosis. However, this has not been proved at the biological or molecular level. Currently, there has not been a microRNA profiling study of patients who have osteosarcoma with and without pathologic fractures that has described differences in terms of microRNA profiling between these two groups and their correlation with biologic behavior.

Questions/purposes: (1) In patients with osteosarcoma of the extremities, how do the microRNA profiles of those with and without pathologic fractures compare? (2) What relationship do microRNAs have with local recurrence, risk of metastasis, disease-specific survival, and overall survival in osteosarcoma patients with pathologic fractures?

Methods: Between 1994 and 2013, 217 patients were diagnosed and treated at our institution for osteosarcoma of the extremities. Patients were excluded if (1) they underwent oncologic resection of the osteosarcoma at an outside institution (two patients) or (2) they were diagnosed with an extraskeletal osteosarcoma (29 patients) or (3) they had less than 1 year of clinical follow-up and no oncologic outcome (local recurrence, metastasis, or death) (four patients). A total of 182 patients were eligible. Of those, 143 were high-grade osteosarcomas. After evaluation of tumor samples before chemotherapy treatment, a total of 80 consecutive samples were selected for sequencing. Demographic and clinical comparison between the sequenced and non-sequenced patients did not demonstrate any differences, confirming that both groups were comparable. Diagnostic samples from the extremities of 80 patients with high-grade extremity osteosarcomas who had not yet received chemotherapy underwent microRNA sequencing for an ongoing large-scale osteosarcoma genome profiling project at our institution. Six samples were removed after a second look by a musculoskeletal pathologist who verified cellularity and quality of samples to be sequenced, leaving a total of 74 patients. Of these, two samples were removed as they were confirmed to be pelvic tumors in a second check after sequencing. The final study sample was 72 patients (11 patients with pathologic fractures and 61 without). Sequencing data were correlated with fractures and local recurrence, risk of metastasis, disease-specific survival, and overall survival through Kaplan-Meier analyses.

Results: Several microRNAs were expressed differently between the two groups. Among the markers with the highest differential expression (edgeR and DESeq algorithms), Hsa-mIR 656-3p, hsa-miR 493-5p, and hsa-miR 381-3p were upregulated in patients with pathologic fractures, whereas hsa-miR 363, hsa-miR 885-5p, and has-miR 20b-5p were downregulated. The highest differential expression fracture and nonfracture-associated microRNA markers also distinguished groups of patients with different metastasis risk, a well as different disease-specific and overall survival. Furthermore, the profile of pathologic fractures demonstrated a higher differential expression for microRNA markers that were previously associated with a higher risk of metastasis and lower survival rates in patients with osteosarcoma.

Conclusions: In patients who have osteosarcoma, the microRNA profiles of those with pathologic fractures are different than of patients without pathologic fractures. The highest differential expression mircroRNA molecules in patients with pathologic fractures predict also higher risk of metastatic disease as well as worse disease-specific survival and overall survival. Furthermore, we found higher differential expression of microRNAs in the pathologic fracture group previously associated with poor prognosis. The higher risk of metastasis and poorer overall survival in patients with pathologic fractures is inherent to tumor aggressive biologic behavior. It is plausible that the fracture itself is not the direct cause of worse prognosis but another manifestation of tumor biologic aggressiveness. Identification of these molecules through liquid biopsies may help to determine which patients may benefit from surgery before fractures occur. The same technology can be applied to identify patterns of response to conventional chemotherapy, assisting in more specific and accurate systemic therapy.

Level Of Evidence Level: III, prognostic study.
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http://dx.doi.org/10.1097/CORR.0000000000000867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000091PMC
September 2019

Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial.

JAMA Oncol 2019 Jul;5(7):1020-1027

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Patients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted.

Objective: To evaluate the margin-negative (R0) resection rate of neoadjuvant FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and losartan followed by chemoradiotherapy for locally advanced pancreatic cancer.

Design, Setting, And Participants: A single-arm phase 2 clinical trial was conducted at a large academic hospital from August 22, 2013, to May 22, 2018, among 49 patients with previously untreated locally advanced unresectable pancreatic cancer as determined by multidisciplinary review. Patients had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 17.1 months (range, 5.0-53.7) among 27 patients still alive at study completion.

Interventions: Patients received FOLFIRINOX and losartan for 8 cycles. Patients with radiographically resectable tumor after chemotherapy received short-course chemoradiotherapy (5 GyE × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine.

Main Outcomes And Measures: R0 resection rate.

Results: Of the 49 patients (26 women and 23 men; median age 63 years [range, 42-78 years]), 39 completed 8 cycles of FOLFIRINOX and losartan; 10 patients had fewer than 8 cycles due to progression (5 patients), losartan intolerance (3 patients), and toxicity (2 patients). Seven patients (16%) had short-course chemoradiotherapy while 38 (84%) had long-course chemoradiotherapy. Forty-two (86%) patients underwent attempted surgery, with R0 resection achieved in 34 of 49 patients (69%; 95% CI, 55%-82%). Overall median progression-free survival was 17.5 months (95% CI: 13.9-22.7) and median overall survival was 31.4 months (95% CI, 18.1-38.5). Among patients who underwent resection, median progression-free survival was 21.3 months (95% CI, 16.6-28.2), and median overall survival was 33.0 months (95% CI, 31.4 to not reached).

Conclusions And Relevance: Total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy provides downstaging of locally advanced pancreatic ductal adenocarcinoma and is associated with an R0 resection rate of 61%.

Trial Registration: ClinicalTrials.gov identifier: NCT01821729.
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http://dx.doi.org/10.1001/jamaoncol.2019.0892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547247PMC
July 2019

Pencil Beam Scanning Proton Beam Chemoradiation Therapy With 5-Fluorouracil and Mitomycin-C for Definitive Treatment of Carcinoma of the Anal Canal: A Multi-institutional Pilot Feasibility Study.

Int J Radiat Oncol Biol Phys 2019 09 22;105(1):90-95. Epub 2019 May 22.

Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Purpose: Definitive chemoradiation with concurrent 5-fluorouracil (5-FU)/mitomycin C (MMC) is an effective treatment for localized anal cancer, but it is associated with significant acute long-term treatment-related toxicity. Pencil beam scanning proton beam (PBS-PT) radiation therapy may potentially reduce this toxicity. This is a multi-institutional pilot study evaluating the feasibility of definitive concurrent chemoradiation with PBS-PT in combination with 5-FU and MMC for carcinoma of the anal canal.

Methods And Materials: Patients were enrolled on a National Cancer Institute-sponsored, prospective, multi-institutional, single-arm pilot study (NCT01858025). Key eligibility criteria included Eastern Cooperative Oncology Group 0 to 2, age ≥18 years, histologically confirmed invasive squamous cell carcinoma of the anal canal, and clinically staged T1-4, N0-3 disease. Patients were treated with PBS-PT per Radiation Therapy Oncology Group 0529 dose schema and concurrent 5-FU/MMC on day 1 and 29. The primary objective of this study was to determine feasibility of PBS-PT with concurrent 5-FU/MMC, defined as grade 3+ dermatologic toxicity less than 48% (reported grade 3+ dermatologic toxicity from Radiation Therapy Oncology Group 98-11). Secondary objectives were to determine the rates of overall grade 3+ toxicities, clinical complete response rate, and disease outcomes.

Results: Between February 2014 and April 2017, we enrolled 25 patients into our study, all of whom were analyzed. Twenty-three patients (92%) completed treatment per protocol, and 2 patients died on treatment. Median time to completion of treatment was 42 days (range, 38-49). The grade 3+ radiation dermatitis rate was 24%. Median follow-up is 27 months (range, 21-50) among the 21 patients still alive. The overall rate of clinical complete response was 88%. The 2-year local failure, colostomy-free survival, progression-free survival, and overall survival are 12%, 72%, 80%, and 84%, respectively.

Conclusions: In our prospective, multi-institutional pilot study of PBS-PT with concurrent 5-FU/MMC, PBS-PT was found to be feasible. A phase 2 study of proton beam radiation therapy is currently underway.
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http://dx.doi.org/10.1016/j.ijrobp.2019.04.040DOI Listing
September 2019

Does the SORG Algorithm Predict 5-year Survival in Patients with Chondrosarcoma? An External Validation.

Clin Orthop Relat Res 2019 Oct;477(10):2296-2303

M. E. R. Bongers, Q. C. B. S. Thio, A.V. Karhade, M. L. Stor, K. A. Raskin, S. A. Lozano-Calderon, Department of Orthopaedic Surgery, Division of Orthopaedic Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA T. F. DeLaney, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA M. L. Ferrone, Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA J. H. Schwab, Department of Orthopaedic Surgery, Division of Orthopaedic Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: We developed a machine learning algorithm to predict the survival of patients with chondrosarcoma. The algorithm demonstrated excellent discrimination and calibration on internal validation in a derivation cohort based on data from the Surveillance, Epidemiology, and End Results (SEER) registry. However, the algorithm has not been validated in an independent external dataset.

Questions/purposes: Does the Skeletal Oncology Research Group (SORG) algorithm accurately predict 5-year survival in an independent patient population surgically treated for chondrosarcoma?

Methods: The SORG algorithm was developed using the SEER registry, which contains demographic data, tumor characteristics, treatment, and outcome values; and includes approximately 30% of the cancer patients in the United States. The SEER registry was ideal for creating the derivation cohort, and consequently the SORG algorithm, because of the high number of eligible patients and the availability of most (explanatory) variables of interest. Between 1992 to 2013, 326 patients were treated surgically for extracranial chondrosarcoma of the bone at two tertiary care referral centers. Of those, 179 were accounted for at a minimum of 5 years after diagnosis in a clinical note at one of the two institutions, unless they died earlier, and were included in the validation cohort. In all, 147 (45%) did not meet the minimum 5 years of followup at the institution and were not included in the validation of the SORG algorithm. The outcome (survival at 5 years) was checked for all 326 patients in the Social Security death index and were included in the supplemental validation cohort, to also ascertain validity for patients with less than 5 years of institutional followup. Variables used in the SORG algorithm to predict 5-year survival including sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location were collected manually from medical records. The tumor characteristics were collected from the postoperative musculoskeletal pathology report. Predicted probabilities of 5-year survival were calculated for each patient in the validation cohort using the SORG algorithm, followed by an assessment of performance using the same metrics as used for internal validation, namely: discrimination, calibration, and overall performance. Discrimination was calculated using the concordance statistic (or the area under the Receiver Operating Characteristic (ROC) curve) to determine how well the algorithm discriminates between the outcome, which ranges from 0.5 (no better than a coin-toss) to 1.0 (perfect discrimination). Calibration was assessed using the calibration slope and intercept from a calibration plot to measure the agreement between predicted and observed outcomes. A perfect calibration plot should show a 45° upwards line. Overall performance was determined using the Brier score, ranging from 0 (excellent prediction) to 1 (worst prediction). The Brier score was compared with the null-model Brier score, which showed the performance of a model that ignored all the covariates. A Brier score lower than the null model Brier score indicated greater performance of the algorithm. For the external validation an F1-score was added to measure the overall accuracy of the algorithm, which ranges between 0 (total failure of an algorithm) and 1 (perfect algorithm).The 5-year survival was lower in the validation cohort than it was in the derivation cohort from SEER (61.5% [110 of 179] versus 76% [1131 of 1544] ; p < 0.001). This difference was driven by higher proportion of dedifferentiated chondrosarcoma in the institutional population than in the derivation cohort (27% [49 of 179] versus 9% [131 of 1544]; p < 0.001). Patients in the validation cohort also had larger tumor sizes, higher grades, and nonextremity tumor locations than did those in the derivation cohort. These differences between the study groups emphasize that the external validation is performed not only in a different patient cohort, but also in terms of disease characteristics. Five-year survival was not different for both patient groups between subpopulations of patients with conventional chondrosarcomas and those with dedifferentiated chondrosarcomas.

Results: The concordance statistic for the validation cohort was 0.87 (95% CI, 0.80-0.91). Evaluation of the algorithm's calibration in the institutional population resulted in a calibration slope of 0.97 (95% CI, 0.68-1.3) and calibration intercept of -0.58 (95% CI, -0.20 to -0.97). Finally, on overall performance, the algorithm had a Brier score of 0.152 compared with a null-model Brier score of 0.237 for a high level of overall performance. The F1-score was 0.836. For the supplementary validation in the total of 326 patients, the SORG algorithm had a validation of 0.89 (95% CI, 0.85-0.93). The calibration slope was 1.13 (95% CI, 0.87-1.39) and the calibration intercept was -0.26 (95% CI, -0.57 to 0.06). The Brier score was 0.11, with a null-model Brier score of 0.19. The F1-score was 0.901.

Conclusions: On external validation, the SORG algorithm retained good discriminative ability and overall performance but overestimated 5-year survival in patients surgically treated for chondrosarcoma. This internet-based tool can help guide patient counseling and shared decision making.

Level Of Evidence: Level III, prognostic study.
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http://dx.doi.org/10.1097/CORR.0000000000000748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999936PMC
October 2019

Radiation-induced and neurofibromatosis-associated malignant peripheral nerve sheath tumors (MPNST) have worse outcomes than sporadic MPNST.

Radiother Oncol 2019 08 9;137:61-70. Epub 2019 May 9.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA; Harvard Medical School, Boston, USA. Electronic address:

Background: Malignant peripheral nerve sheath tumors (MPNST) may be sporadic or associated with neurofibromatosis or prior radiation. MPNST may behave aggressively with a high rate of local recurrence and distant metastasis.

Methods: In an IRB approved protocol, we reviewed the clinical characteristics, treatment, and outcomes of 280 patients treated for MPNST at Massachusetts General Hospital (MGH) between 1960 and 2016.

Results: There were 138 men and 142 women with a median age of 41 (range: 3-95) years. Tumors were classified as neurofibromatosis-associated (nfMPNST, n = 77), radiation-induced (rMPNST, n = 21), or sporadic (sMPNST, n = 182) MPNST. The median time to development of rMPNST from prior radiation was 15 years. With a median follow-up of 43.1 months, the median overall survival (OS) was 65.3 months. Older age, nfMPNST, rMPNST, increased tumor size, lymph node involvement, metastatic disease, intermediate to high grade, radiotherapy alone, and R2 resection were related to worse OS, whereas surgery with radiotherapy was associated with improved OS. Among the 251 patients without metastasis, nfMPNST, rMPNST, and increased tumor size were correlated with worse metastasis-free survival; nfMPNST, radiotherapy alone, and R1/R2 resection were associated with local recurrence, whereas surgery with adjuvant radiotherapy was related to improved local control in patients with R1/R2 resection.

Conclusions: Both radiation-induced and neurofibromatosis-associated MPNSTs have poorer prognosis than sporadic MPNSTs. Complete resection of the tumor is a significant prognostic factor for MPNST. The addition of radiotherapy after surgery should be considered especially when the surgical margins are positive.
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http://dx.doi.org/10.1016/j.radonc.2019.03.015DOI Listing
August 2019
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