Publications by authors named "Patrick J Boland"

74 Publications

Postoperative extremity compartment syndrome in a cancer center: Incidence and risk factors.

Surg Oncol 2021 Apr 3;38:101563. Epub 2021 Apr 3.

Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Objective: Postoperative compartment syndrome is a reported complication with known patient- and treatment-specific risk factors. Cancer patients carry unique risk factors associated with their underlying disease and long, complex procedures. While elevated serum lactate in traumatic and intensive care settings portends higher risk, no laboratory parameter has demonstrated utility in postoperative risk stratification. Postoperative extremity compartment syndrome in the study institution's cancer population was examined and whether intraoperative serum lactate correlates with postoperative compartment syndrome risk was investigated.

Methods: A 1:2 case-control study was performed, which compared cancer patients with postoperative compartment syndrome to those who underwent similar surgical procedures without this complication. Twelve patients were matched to 24 controls by sex, age, surgical procedures, and duration of surgery. Patient and operative variables were analyzed for prognostic significance.

Results: The compartment syndrome rate was 0.09% of all cases (n = 13,491); 0.12% of cases ≥ 3 h' duration (n = 9,979), and 0.25% of cases ≥ 5 h (n = 4,811). Compared with controls, the case group had higher median BMI (31.7 kg/m2 vs. 25.4 kg/m2, P = 0.001), and median intraoperative lactate level (4.05 mmol/L vs. 1.5 mmol/L, P = 0.047).

Conclusion: Our institutional incidence of postoperative compartment syndrome was similar to that of non-oncologic institutions. While many traditional risk factors did not prove to be influential in our patients, elevated median body mass index and intraoperative serum lactate were identified as risk factors for postoperative compartment syndrome in a cancer population.
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http://dx.doi.org/10.1016/j.suronc.2021.101563DOI Listing
April 2021

Minimal clinically important differences in SF-36 global score: Current value in orthopedic oncology.

J Orthop Res 2020 Dec 8. Epub 2020 Dec 8.

Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

The SF-36 is widely used to evaluate the health-related quality of life (HRQoL) of patients with musculoskeletal tumors. Instead of typical methods, calculating the SF-36 Global Score has recently become an increasingly common reporting approach. However, numerical changes lack clear clinical relevance. The minimal clinically important difference (MCID) is useful for interpreting changes in functional scores by defining the smallest change patients may perceive as clinically meaningful. The aim of this study is to determine the MCID of the SF-36 Global Score in orthopedic oncology patients, which has not been reported to date. Three-hundred ten patients who underwent surgery and completed two surveys during postoperative follow-up were reviewed. The two most common methods for calculating the SF-36 Global Score were used: (1) anchor-based methods and receiver operating characteristic analysis based on one-half of the SD of change score and standard error of measurement at baseline and; (2) distribution-based methods. Using anchor-based methods, the MCIDs of SF-36 Global Scores #1 and #2 were 2.7 (area under the curve [AUC] = 0.85) and 2.5 (AUC = 0.79) for improvement, and -1.5 (AUC = 0.81) and -0.6 (AUC = 0.83) for deterioration, respectively. Using distribution-based methods, the MCIDs of SF-36 Global Scores #1 and #2 were 4.1 and 4.4 by half SD, and 4.1 and 4.5 by standard error of measurement, respectively. Our findings provide benchmark values, which can serve as a reference for future studies in musculoskeletal tumor patients using the SF-36 Global Score as a single measure for HRQoL.
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http://dx.doi.org/10.1002/jor.24944DOI Listing
December 2020

The critical difference in the DASH (Disabilities of the Arm, Shoulder, and Hand) outcome measure after essential upper extremity tumor surgery.

J Shoulder Elbow Surg 2021 Jan 20. Epub 2021 Jan 20.

Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

Background: The DASH (Disabilities of the Arm, Shoulder, and Hand) is a scored questionnaire that is widely used to evaluate the health-related quality of life of patients with upper limb musculoskeletal disorders. However, numerical changes in the measure scores lack clinical significance without meaningful threshold change values of outcome measures that are diagnostically specific. The minimal clinically important difference (MCID) is useful for the interpretation of scores by defining the smallest change that a patient would perceive. However, the MCIDs of the scores in orthopedic oncology patients has not been reported. We aimed to determine the MCIDs of the measure in orthopedic oncology patients.

Methods: Data from our health-related quality of life database from 1999 to 2005 were retrospectively reviewed after institutional review board approval. Seventy-eight patients who underwent surgery and completed 2 surveys during postoperative follow-up were evaluated. Two different methods were used to estimate the MCIDs: distribution-based and anchor-based approaches (the latter used receiver operating characteristic analysis).

Results: Using distribution-based methods, the MCIDs of the DASH questionnaire were 7.4 and 8.3 by half standard deviation and the 90% interval of minimal detectable change, respectively. By anchor-based method (receiver operating characteristic analysis), the MCID was 8.3.

Conclusion: The MCID values calculated by each method validates that the results for upper extremity oncology patients were similar to those reported in other orthopedic conditions. These results identify the threshold for meaningful improvements in DASH scores in orthopedic oncology patients and establish the reference to evaluate health-related quality of life and the outcomes of upper extremity oncology surgery. These data should be further refined for disease- and reconstruction-specific analyses.
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http://dx.doi.org/10.1016/j.jse.2020.11.027DOI Listing
January 2021

Finn/Orthopaedic Salvage System Distal Femoral Rotating-Hinge Megaprostheses in Oncologic Patients: Long-Term Complications, Reoperations, and Amputations.

J Bone Joint Surg Am 2021 Apr;103(8):705-714

Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY.

Background: There is a lack of evidence regarding long-term outcomes of rotating-hinge knee prostheses with distal femoral replacement in a large oncologic patient series. In this study, we investigated the proportion of patients experiencing complications requiring surgery in the long term, as well as the cumulative incidence of implant removal/revision and amputation at 5, 10, 15, and 20 years through competing risk analyses.

Methods: We retrospectively studied 214 patients treated with a Finn/Orthopaedic Salvage System (OSS) knee prosthesis (Zimmer Biomet) after distal femoral resection from 1991 to 2017. The study end points were postoperative complications requiring surgery. Reoperations were classified as major when there was (1) removal of the metal-body femoral component, the tibial component, or the bone-implant fixation; (2) major revision (exchange of the metal-body femoral component, the tibial component, or the bone-implant fixation); or (3) amputation. Minor reoperations were defined as all other reoperations. Competing risk analysis was used to estimate the cumulative incidence of implant removal/revision or amputation.

Results: There were 312 reoperations in 113 patients (98 major reoperations in 68 patients and 214 minor reoperations). Seventeen patients (8%) required ≥5 additional operations, and 21 patients (10%) required >1 major reoperation. Although the number of reoperations decreased over time, major and minor reoperations continuously accrued after 10 years. The cumulative incidences of implant removal or revision for any reason at 5, 10, 15, and 20 years were 22.6%, 30.1%, 34.3%, and 42.5%, respectively. Although most implant removals/revisions occurred in the first 10 years, the risk persisted after 10 years, at a mean of 1.24%/year, mainly due to deep infection (1.06%/year).

Conclusions: The long-term outcomes of treatment with a Finn/OSS distal femoral rotating-hinge knee prosthesis showed it to be a durable reconstruction technique. The rate of implant removal/revisions after 10 years was gradual (1.24%/year). Deep infection remains a major late-failure mechanism, and lifetime surveillance for prosthetic problems is needed.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.20.00696DOI Listing
April 2021

Chromosome 3p loss of heterozygosity and reduced expression of H3K36me3 correlate with longer relapse-free survival in sacral conventional chordoma.

Hum Pathol 2020 10 12;104:73-83. Epub 2020 Aug 12.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. Electronic address:

Conventional chordoma is a rare slow-growing malignant tumor of notochordal origin primarily arising at the base of the skull and sacrococcygeal bones. Chordoma may arise from its benign counterpart, benign notochordal cell tumors, and can also undergo dedifferentiation progressing into dedifferentiated chordoma. No study has directly compared the genomic alterations among these tumors comprising a morphologic continuum. Our prior study identified frequent chromosome 3p loss of heterozygosity and minimal deleted regions on chromosome 3 encompassing SETD2, encoding a histone methyltransferase involved in histone H3 lysine 36 trimethylation (H3K36me3). In the present study, we expanded our study to include 65 sacral conventional chordoma cases, 3 benign notochordal cell tumor cases, and 2 dedifferentiated chordoma cases using single nucleotide polymorphism (SNP) array, targeted next-generation sequencing analysis, and immunohistochemistry. We performed immunohistochemical analysis of histone, H3K36me3, and investigated whether there is any association between the clinical behavior and recurrent chromosome or aneuploidy or H3K36me3 protein expression. We found that there is increased genomic instability from benign notochordal cell tumor to conventional chordoma to dedifferentiated chordoma. The highly recurrent genomic aberration, chromosome 3p loss of heterozygosity (occurred in 70% of conventional chordomas), is correlated with longer relapse-free survival, but not with overall survival or metastasis-free survival in sacral chordoma. Chordomas demonstrate variable patterns and levels of H3K36me3 expression, and reduced expression of H3K36me3 showed marginally significant correlation with longer relapse-free survival. Copy number alterations in the genes encoding the H3K36me3 methylation transferase complex and demethylase may account for the altered H3K36me3 expression levels.
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http://dx.doi.org/10.1016/j.humpath.2020.07.002DOI Listing
October 2020

What Are the Minimum Clinically Important Differences in SF-36 Scores in Patients with Orthopaedic Oncologic Conditions?

Clin Orthop Relat Res 2020 09;478(9):2148-2158

K. Ogura, M. A. Yakoub, A. B. Christ, T. Fujiwara, Z. Nikolic, P. J. Boland, J. H. Healey, Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: The SF-36 is widely used to evaluate the health-related quality of life of patients with musculoskeletal tumors. The minimum clinically important difference (MCID) is useful for interpreting changes in functional scores because it defines the smallest change each patient may perceive. Since the MCID is influenced by the population characteristics, MCIDs of the SF-36 should be defined to reflect the specific conditions of orthopaedic oncology patients.

Questions/purposes: (1) What is the MCID of SF-36 physical component summary (PCS) and mental component summary (MCS) scores in patients with orthopaedic oncologic conditions when calculated with distribution-based methods? (2) What is the MCID of SF-36 PCS and MCS scores in patients with orthopaedic oncologic conditions when calculated by anchor-based methods?

Methods: Of all 960 patients who underwent surgery from 1999 to 2005, 32% (310) of patients who underwent musculoskeletal oncologic surgery and completed two surveys during postoperative follow-up were reviewed. We evaluated a dataset that ended in 2005, completing follow-up of data accrued as part of the cooperative effort between the American Academy of Orthopaedic Surgeons and the Council of Musculoskeletal Specialty Societies to create patient reported quality of life instruments for lower extremity conditions. This effort, started in 1994 was validated and widely accepted by its publication in 2004. We believe the findings from this period are still relevant today because (1) this critical information has never been available for clinicians and researchers to distinguish real differences in outcome among orthopaedic oncology patients, (2) the SF-36 continues to be the best validated and widely used instrument to assess health-related quality of life, and unfortunately (3) there has been no significant change in outcome for oncology patients over the intervening years. SF-36 PCS and MCS are aggregates of the eight scale scores specific to physical and mental dimension (scores range from 0 to 100, with higher scores representing better health). Their responsiveness has been shown postoperatively for several surgical procedures (such as, colorectal surgery). Two different methods were used to calculate the MCID: the distribution-based method, which was based on half the SD of the change in score and standard error of the measurement at baseline, and anchor-based, in which a receiver operating characteristic (ROC) curve analysis was performed. The anchor-based method uses a plain-language question to ask patients how their individual conditions changed when compared with the previous survey. Answer choices were "much better," "somewhat better," "about the same," "somewhat worse," or "much worse." The ROC curve-derived MCIDs were defined as the change in scores from baseline, with sensitivity and specificity to detect differences in patients who stated their outcome was, about the same and those who stated their status was somewhat better or somewhat worse. This approach is based on each patient's perception. It considers that the definition of MCID is the minimal difference each patient can perceive as meaningful.

Results: Using the distribution-based method, we found that the MCIDs of the PCS and MCS were 5 and 5 by half the SD, and 6 and 5 by standard error of the measurement. In the anchor-based method, the MCIDs of the PCS and MCS for improvement/deterioration were 4 (area under the curve, 0.82)/-2 (area under the curve, 0.79) and 4 (area under the curve, 0.72)/ (area under the curve, 0.68), respectively.

Conclusions: Since both anchor-based and distribution-based MCID estimates of the SF-36 in patients with musculoskeletal tumors were so similar, we have confidence in the estimates we made, which were about 5 points for both the PCS and the MCS subscales of the SF-36. This suggests that interventions improving SF-36 by less than that amount are unlikely to be perceived by patients as clinically important. Therefore, those interventions may not justify exposing patients to risk, cost, or inconvenience. When applying new interventions to orthopaedic oncology patients going forward, it will be important to consider these MCIDs for evaluation purposes.

Level Of Evidence: Level III, diagnostic study.
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http://dx.doi.org/10.1097/CORR.0000000000001341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431256PMC
September 2020

Rate and risk factors for wound complications after internal hemipelvectomy.

Bone Joint J 2020 Mar;102-B(3):280-284

Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Affiliated with Weill Medical College of Cornell University, New York, New York, USA.

Aims: Although internal hemipelvectomy is associated with a high incidence of morbidity, especially wound complications, few studies have examined rates of wound complications in these patients or have identified factors associated with the consequences. The present study aimed to: 1) determine the rate of wound and other complications requiring surgery after internal hemipelvectomy; and 2) identify factors that affect the rate of wound complications and can be used to stratify patients by risk of wound complications.

Methods: The medical records of 123 patients undergoing internal hemipelvectomy were retrospectively reviewed, with a focus on both overall complications and wound complications. Logistic regression analyses were performed to examine the association between host, tumour, and surgical factors and rates of postoperative wound complications.

Results: The overall rate of postoperative complications requiring surgery was 49.6%. Wound complications were observed in 34.1% of patients, hardware-related complications in 13.2%, graft-related complications in 9.1%, and local recurrence in 5.7%. On multivariate analysis, extrapelvic tumour extension (odds ratio (OR) 23.28; 95% confidence interval (CI), 1.97 to 274.67; p = 0.012), both intra- and extrapelvic tumour extension (OR 46.48; 95% CI, 3.50 to 617.77; p = 0.004), blood transfusion ≥ 20 units (OR 50.28; 95% CI, 1.63 to 1550.32; p = 0.025), vascular sacrifice of the internal iliac artery (OR 64.56; 95% CI, 6.33 to 658.43; p < 0.001), and use of a structural allograft (OR, 6.57; 95% CI, 1.70 to 25.34; p = 0.001) were significantly associated with postoperative wound complications.

Conclusion: Internal hemipelvectomy is associated with high rates of morbidity, especially wound complications. Several host, tumour, and surgical variables are associated with wound complications. The ability to stratify patients by risk of wound complications can help refine surgical and wound-healing planning and may lead to better outcomes in patients undergoing internal hemipelvectomy. Cite this article: 2020;102-B(3):280-284.
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http://dx.doi.org/10.1302/0301-620X.102B3.BJJ-2019-1329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123980PMC
March 2020

Association between patient age and the risk of mortality following local recurrence of a sacral chordoma.

J Surg Oncol 2019 Nov 22. Epub 2019 Nov 22.

University Musculoskeletal Oncology Unit, Division of Orthopaedic Surgery, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

Background: Local recurrence (LR) of sacral chordoma is a difficult problem and the mortality risk associated with LR remains poorly described. The purpose of this study was to evaluate the risk of mortality in patients with LR and determine if patient age is associated with mortality.

Methods: A total of 218 patients (144 male, 69 female; mean age 59 ± 15 years) with sacrococcygeal chordomas were reviewed. Cumulative incidence functions and competing risks for death due to disease and nondisease mortality were employed to analyze mortality trends following LR.

Results: The 10-year overall survival (OS) was 55%. Patients with LR had 44% 10-year OS, similar to patients without (59%; P = .38). The 10-year OS between those less than 55 compared with ≥55 years were similar (69% vs 48%; P = .52). The 10-year death due to disease was worse in patients with LR compared with those without (44% vs 84%; P < .001). In patients without LR, patients ≥55 years were 1.6-fold more likely to experience death due to other causes.

Conclusions: Patients with an LR are more likely to die due to disease. Advanced patient age was associated with higher all-cause mortality following resection of sacral chordoma. LR of chordoma was associated with increased disease-specific mortality, regardless of age.
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http://dx.doi.org/10.1002/jso.25774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242148PMC
November 2019

Genomic Profiling Identifies Association of Mutation with Longer Relapse-Free and Metastasis-Free Survival in High-Grade Chondrosarcoma.

Clin Cancer Res 2020 01 15;26(2):419-427. Epub 2019 Oct 15.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Chondrosarcomas are the second most common primary malignant bone tumors. Although histologic grade is the most important factor predicting the clinical outcome of chondrosarcoma, it is subject to interobserver variability. Isocitrate dehydrogenase 1 () and hotspot mutations were recently found to be frequently mutated in central chondrosarcomas. However, a few published articles have been controversial regarding the association between mutation status and clinical outcomes in chondrosarcomas.

Experimental Design: We performed hotspot sequencing of and genes in 89 central chondrosarcomas and targeted next-generation sequencing in 54 of them, and then correlated the mutation status with the patient's clinical outcome.

Results: Although no association was discovered between mutation status and the patient's overall survival, / mutation was found to be associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas. Genomic profiling reveals gene amplification and mutation, for the first time, in addition to promoter mutation in a subset (6/30, 20%) of high-grade and dedifferentiated chondrosarcomas. These abnormalities in telomere genes are concurrent with / mutation and with deletion or mutation, suggesting a possible association and synergy among these genes in chondrosarcoma progression. We found 21% of patients with chondrosarcoma also had histories of second malignancies unrelated to cartilaginous tumors, suggesting possible unknown genetic susceptibility to chondrosarcoma.

Conclusions: mutations are associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas, and they tend to co-occur with mutations and with and alterations in a subset of high-grade chondrosarcomas.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-4212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980683PMC
January 2020

Treatment of dedifferentiated chordoma: a retrospective study from a large volume cancer center.

J Neurooncol 2019 Sep 23;144(2):369-376. Epub 2019 Jul 23.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 22, New York, NY, 10065, USA.

Objective: Dedifferentiated chordomas (DC) are genetically and clinically distinct from conventional chordomas (CC), exhibiting frequent SMARCB1 alterations and a more aggressive clinical course. We compared treatment and outcomes of DC and CC patients in a retrospective cohort study from a single, large-volume cancer center.

Methods: Overall, 11 DC patients were identified from 1994 to 2017 along with a cohort of 68 historical control patients with CC treated during the same time frame. Clinical variables and outcomes were collected from the medical record and Wilcoxon rank sum or Fisher exact tests were used to make comparisons between the two groups. Kaplan-Meier survival analysis and log-rank tests were used to compare DC and CC overall survival.

Results: DC demonstrated a bimodal age distribution at presentation (36% age 0-24; 64% age > 50). DC patients more commonly presented with metastatic disease than CC patients (36% vs. 3% p = 0.000). DC patients had significantly shorter time to local treatment failure after radiation therapy (11.1 months vs. 34.1 months, p = 0.000). The rate of distant metastasis following treatment was significantly higher in DC compared to CC (57% vs. 5%, p = 0.000). The median overall survival after diagnosis for DC was 20 months (95% CI 0-48 months) compared to 155 months (95% CI 94-216 months) for CC (p = 0.007).

Conclusion: DC patients exhibit significantly higher rates of both synchronous and metachronous metastases, as well as shorter overall survival rates compared to conventional chordoma. The relatively poor survival outcomes with conventional therapies indicate the need to study targeted therapies for the treatment of DC.
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http://dx.doi.org/10.1007/s11060-019-03239-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594172PMC
September 2019

Should the Use of Biologic Agents in Patients With Renal and Lung Cancer Affect Our Surgical Management of Femoral Metastases?

Clin Orthop Relat Res 2019 04;477(4):707-714

C. J. Gutowski, MD Anderson Cancer Center at Cooper, Department of Orthopaedic Surgery, Cooper University Hospital, Camden, NJ, USA C. J. Gutowski, N. Fabbri, P. J. Boland, J. H. Healey, Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA B. Zmistowski, Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA N. Fabbri, P. J. Boland, J. H. Healey, Department of Surgery, Weill Cornell Medical College, New York, NY, USA.

Background: Biologic agents may prolong survival of patients with certain kidney and lung adenocarcinomas that have metastasized to bone, and patient response to these agents should be considered when choosing between an endoprosthesis and internal fixation for surgical treatment of femoral metastases.

Questions/purposes: Among patients undergoing surgery for femoral metastases of lung or renal cell carcinoma, (1) Does survival differ between patients who receive only cytotoxic chemotherapy and those who either respond or do not respond to biologic therapy? (2) Does postsurgical incidence of local disease progression differ between groups stratified by systemic treatment and response? (3) Does implant survival differ among groups stratified by systemic treatment and response?

Methods: From our institutional longitudinally maintained orthopaedic database, patients were identified by a query initially identifying all patients who carried a diagnosis of renal cell carcinoma or lung carcinoma. Patients who underwent internal fixation or prosthetic reconstruction between 2000 and 2016 for pathologic fracture of the femur and who survived ≥ 1 year after surgery were studied. Patients who received either traditional cytotoxic chemotherapy or a biologic agent were included. Patients were classified as responders or nonresponders to biologic agents based on whether they had clinical and imaging evidence of a response recorded on two consecutive office visits over ≥ 6 months. Endpoints were overall survival from the time of diagnosis, survival after the femoral operation, evidence of disease progression in the femoral operative site, and symptomatic local disease progression for which revision surgery was necessary. Our analysis included 148 patients with renal (n = 26) and lung (n = 122) adenocarcinoma. Fifty-one patients received traditional chemotherapy only. Of 97 patients who received a biologic agent, 41 achieved a response (stabilization/regression of visceral metastases), whereas 56 developed disease progression. We analyzed overall patient survival with the Kaplan-Meier method and used the log-rank test to identify significant differences (p < 0.05) between groups.

Results: One-year survival after surgery among patients responsive to biologic therapy was 61% compared with 20% among patients nonresponsive to biologics (p < 0.001) and 10% among those who received chemotherapy only (p < 0.009). With the number of patients we had to study, we could not detect any difference in local progression of femoral disease associated with systemic treatment and response. Radiologic evidence of periimplant local disease progression developed in three (7%) of 41 patients who responded to biologic treatment, two (3%) of 56 patients nonresponsive to biologics, and one (2%) of 51 patients treated with traditional chemotherapy. With the numbers of patients we had, we could not detect a difference in patients who underwent revision. All three patients responsive to biologics who developed local recurrence underwent revision, whereas the two without a response to biologics did not.

Conclusions: Biologic therapy improves the overall longevity of some patients with lung and renal metastases to the femur in whom a visceral disease response occurred. In our limited cohort, we could not demonstrate an implant survival difference between such patients and those with shorter survival who may have had more aggressive disease. However, an increased life expectancy beyond 1 year among patients responsive to biologics may increase risk of mechanical failure of fixation constructs.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000000434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437361PMC
April 2019

Low dose radiotherapy is associated with local complications but not disease control in sacral chordoma.

J Surg Oncol 2019 Jun 7;119(7):856-863. Epub 2019 Feb 7.

Division of Orthopaedic Surgery, Department of Surgery, University Musculoskeletal Oncology Unit Mount Sinai Hospital, University of Toronto, Toronto, Canada.

Background: We reviewed the disease control and complications of the treatment of sacrococcygeal chordoma from four tertiary cancer centers with emphasis on the effects of radiotherapy in surgically treated patients.

Methods: A total of 193 patients with primary sacrococcygeal chordoma from 1990 to 2015 were reviewed. There were 124 males, with a mean age of 59 ± 15 years and a mean follow-up of 7 ± 4 years. Eighty-nine patients received radiotherapy with a mean total dose of 61.8 ± 10.9 Gy.

Results: The 10-year disease-free and disease-specific survival was 58% and 72%, respectively. Radiation was not associated with local recurrence (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.59-2.17; P = 0.71), metastases (HR, 0.93; 95% CI, 0.45-1.91; P = 0.85) or disease-specific survival (HR, 0.96; 95% CI, 0.46-2.00; P = 0.91). Higher doses (≥70 Gy; HR, 0.52; 95% CI, 0.20-1.32; P = 0.17) may be associated with reduced local recurrence. Radiotherapy was associated with wound complications (HR, 2.76; 95% CI, 1.64-4.82;, P < 0.001) and sacral stress fractures (HR, 4.73; 95% CI, 1.88-14.38; P < 0.001).

Conclusions: In this multicenter review, radiotherapy was not associated with tumor outcome but associated with complications. The routine use of radiotherapy with en-bloc resection of sacrococcygeal chordomas should be reconsidered in favor of a selective, individualized approach with a radiation dose of ≥70 Gy.
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http://dx.doi.org/10.1002/jso.25399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746225PMC
June 2019

Chemotherapy Curtails Bone Formation From Compliant Compression Fixation of Distal Femoral Endoprostheses.

Clin Orthop Relat Res 2019 01;477(1):206-216

Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA, affiliated with Weill Medical College of Cornell University.

Background: Modulated compliant compressive forces may contribute to durable fixation of implant stems in patients with cancer who undergo endoprosthetic reconstruction after tumor resection. Chemotherapy effects on bone hypertrophy and osteointegration have rarely been studied, and no accepted radiologic method exists to evaluate compression-associated hypertrophy.

Questions/purposes: (1) What was the effect of chemotherapy on the newly formed bone geometry (area) at 1 year and the presumed osteointegration? (2) What clinical factors were associated with the degree of hypertrophy? (3) Did the amount of bone formation correlate with implant fixation durability? (4) Was the amount of new bone generation or chemotherapy administration correlated with Musculoskeletal Tumor Society (MSTS) score?

Methods: Between 1999 and 2013, we performed 245 distal femoral reconstructions for primary or revision oncologic indications. We evaluated 105 patients who received this implant. Ten were excluded because they lacked 2 years of followup and two were lost to followup, leaving 93 patients for review. All underwent distal femur reconstruction with the compliant compressive fixation prosthesis; 49 received postoperative chemotherapy and 44 did not. During this period, the implant was used for oncology patients < 60 years of age without metastases and with > 8 cm of intact, nonirradiated bone distal to the lesser trochanter and ≥ 2.5 mm of cortex. Our cohort included patients with painful loosening of cemented or uncemented stemmed femoral megaprostheses when revision with the compliant compressive device was feasible. Patients with high-grade sarcomas all received chemotherapy, per active Children's Oncology Group protocols, for their tumor diagnosis. At each imaging time point (3, 6, 9, 12, 18, 24 months), we measured the radiographic area of the bone under compression using National Institutes of Health open-access software, any shortening of the spindle-anchor plug segment distance as reflected by the exposed traction bar length, and prosthesis survivorship. Clinical and functional status and MSTS scores were recorded at each followup visit. Duration of prosthesis retention without aseptic loosening or mechanical failure was evaluated using Kaplan-Meier analysis, censoring patients at last followup.

Results: Chemotherapy was associated with the amount of overall bone formation in a time-dependent fashion. In the 12 months after surgery there was more bone formation in patients who did not receive postoperative chemotherapy than those who did (60.2 mm, confidence interval [CI] 49.3-71.1 versus 39.1, CI 33.3-44.9; p = 0.001). Chemotherapy was not associated with prosthesis survival. Ten-year implant survival was 85% with chemotherapy and 88% without chemotherapy (p = 0.74). With the number of patients we had, we did not identify any clinical factors that were associated with the amount (area) of hypertrophy. The hypertrophied area was not associated with the durability of implant fixation. MSTS scores were lower in patients treated with chemotherapy (25 versus 28; p = 0.023), but were not correlated with new bone formation.

Conclusions: The relationships among chemotherapy, bone formation, and prosthetic survivorship are complex. Because bone formation is less in the first year when the patient is being treated with chemotherapy, it is not clear if the rehabilitation schedule should be different for those patients receiving chemotherapy compared with those who do not. The relationship between early bone formation and the timing of weightbearing rehabilitation should be evaluated in a multicenter study.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000000512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345286PMC
January 2019

Tumor Xenografts of Human Clear Cell Renal Cell Carcinoma But Not Corresponding Cell Lines Recapitulate Clinical Response to Sunitinib: Feasibility of Using Biopsy Samples.

Eur Urol Focus 2017 12 25;3(6):590-598. Epub 2016 Aug 25.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

Background: Parallel development of preclinical models that recapitulate treatment response observed in patients is central to the advancement of personalized medicine.

Objective: To evaluate the use of biopsy specimens to develop patient-derived xenografts and the use of corresponding cell lines from renal cell carcinoma (RCC) tumors for the assessment of histopathology, genomics, and treatment response.

Design, Setting, And Participants: A total of 74 tumor specimens from 66 patients with RCC were implanted into immunocompromised NOD-SCID IL2Rg mice. Four cell lines generated from patients' specimens with clear cell pathology were used for comparative studies.

Outcome Measurements And Statistical Analysis: Preclinical models were established and assessed. Engraftment rates were analyzed using chi-square testing. Analysis of variance (two-way analysis of variance) was conducted to assess tumor growth.

Results And Limitations: Overall, 33 RCC mouse xenograft models were generated with an overall engraftment rate of 45% (33 of 74). Tumor biopsies engrafted comparably with surgically resected tumors (58% vs 41%; p=0.3). Xenograft tumors and their original tumors showed high fidelity in regard to histology, mutation status, copy number change, and targeted therapy response. Engraftment rates from metastatic tumors were higher but not more significant than primary tumors (54% vs 34%; p=0.091). Our engraftment rate using metastases or biopsies was comparable with recent reports using resected primary tumors. In stark contrast to corresponding cell lines, all tested xenografts recapitulated patients' clinical response to sunitinib.

Conclusions: Patient-derived xenograft models can be effectively established from tumor biopsies. Preclinical xenograft models but not matched cell lines reflected clinical responses to sunitinib.

Patient Summary: Matched patient-derived clear cell renal cell carcinoma xenografts and cell lines from responsive and refractory patients treated with sunitinib were established and evaluated for pharmacologic response to anti-vascular endothelial growth factor treatment. Both models accurately reflected the genetic characteristics of original tumors, but only xenografts recapitulated drug responses observed in patients. These models could serve as a powerful platform for precision medicine.
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http://dx.doi.org/10.1016/j.euf.2016.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608640PMC
December 2017

CORR Insights: Use of Compressive Osteointegration Endoprostheses for Massive Bone Loss From Tumor and Failed Arthroplasty: A Viable Option in the Upper Extremity.

Authors:
Patrick J Boland

Clin Orthop Relat Res 2017 06 3;475(6):1712-1715. Epub 2017 Apr 3.

Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

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http://dx.doi.org/10.1007/s11999-017-5332-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406361PMC
June 2017

Retrospective Review of Atypical Femoral Fracture in Metastatic Bone Disease Patients Receiving Denosumab Therapy.

Oncologist 2017 04 8;22(4):438-444. Epub 2017 Mar 8.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Denosumab therapy is used to reduce skeletal-related events in metastatic bone disease (MBD). There have been reports of atypical femoral fracture (AFF) in osteoporotic patients treated with denosumab but none in the context of higher dose and more frequent denosumab therapy for MBD. The goal of this study was to assess the incidence of AFF in MBD.

Patients And Methods: We conducted a retrospective review of 253 patients who received a minimum of 12 doses of denosumab at 120 mg each for MBD. To identify patients with asymptomatic atypical stress reactions in the lateral subtrochanteric femur (which precede fractures), we reviewed the skeletal images of 66 patients who had received at least 21 doses of denosumab for AFF features.

Results: These patients received a median of 17 doses, with a median treatment duration of 23 months. There was 1 case of undiagnosed clinical AFF detected after chart review and 2 cases of subclinical atypical femoral stress reaction observed on imaging review after 23 doses of denosumab over 33 months, 28 doses over 27 months, and 21 doses over 21 months, respectively. Scout computed tomography films showed diffuse cortical thickening of diaphysis with localized periosteal reaction of lateral femoral cortex. Bone scan and magnetic resonance imaging scan of 2 patients with stress reactions confirmed the diagnosis.

Conclusion: The incidence of clinical AFF in this context is 0.4% (1/253; 95% confidence interval [CI] 0.1%-2.2%), and the incidence of atypical femoral stress reaction based on imaging review is 4.5% (3/66; 95% CI 1.6%-12.5%). Clinicians should be aware of the clinical prodrome (which may or may not be present) and antecedent imaging changes associated with AFF. 2017;22:438-444 Among patients with metastatic bone disease treated with denosumab, cases of clinical and subclinical atypical femoral fracture (AFF) are rare. The one detected case of clinical fracture went unrecognized despite prodromic symptoms. Clinicians should be aware of (a) the potential prodrome of anterior thigh/groin pain and (b) subclinical imaging changes in the lateral femur, both of which may precede clinical AFF.
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http://dx.doi.org/10.1634/theoncologist.2016-0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388375PMC
April 2017

Can We Estimate Short- and Intermediate-term Survival in Patients Undergoing Surgery for Metastatic Bone Disease?

Clin Orthop Relat Res 2017 Apr 1;475(4):1252-1261. Epub 2016 Dec 1.

Orthopaedic Surgery Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center and Weill College of Medicine, Cornell University, New York, NY, USA.

Background: Objective means of estimating survival can be used to guide surgical decision-making and to risk-stratify patients for clinical trials. Although a free, online tool ( www.pathfx.org ) can estimate 3- and 12-month survival, recent work, including a survey of the Musculoskeletal Tumor Society, indicated that estimates at 1 and 6 months after surgery also would be helpful. Longer estimates help justify the need for more durable and expensive reconstructive options, and very short estimates could help identify those who will not survive 1 month and should not undergo surgery. Thereby, an important use of this tool would be to help avoid unsuccessful and expensive surgery during the last month of life.

Questions/purposes: We seek to provide a reliable, objective means of estimating survival in patients with metastatic bone disease. After generating models to derive 1- and 6-month survival estimates, we determined suitability for clinical use by applying receiver operator characteristic (ROC) (area under the curve [AUC] > 0.7) and decision curve analysis (DCA), which determines whether using PATHFx can improve outcomes, but also discerns in which kinds of patients PATHFx should not be used.

Methods: We used two, existing, skeletal metastasis registries chosen for their quality and availability. Data from Memorial Sloan-Kettering Cancer Center (training set, n = 189) was used to develop two Bayesian Belief Networks trained to estimate the likelihood of survival at 1 and 6 months after surgery. Next, data from eight major referral centers across Scandinavia (n = 815) served as the external validation set-that is, as a means to test model performance in a different patient population. The diversity of the data between the training set from Memorial Sloan-Kettering Cancer Center and the Scandinavian external validation set is important to help ensure the models are applicable to patients in various settings with differing demographics and treatment philosophies. We considered disease-specific, laboratory, and demographic information, and the surgeon's estimate of survival. For each model, we calculated the area under the ROC curve (AUC) as a metric of discriminatory ability and the Net Benefit using DCA to determine whether the models were suitable for clinical use.

Results: On external validation, the AUC for the 1- and 6-month models were 0.76 (95% CI, 0.72-0.80) and 0.76 (95% CI, 0.73-0.79), respectively. The models conferred a positive net benefit on DCA, indicating each could be used rather than assume all patients or no patients would survive greater than 1 or 6 months, respectively.

Conclusions: Decision analysis confirms that the 1- and 6-month Bayesian models are suitable for clinical use.

Clinical Relevance: These data support upgrading www.pathfx.org with the algorithms described above, which is designed to guide surgical decision-making, and function as a risk stratification method in support of clinical trials. This updating has been done, so now surgeons may use any web browser to generate survival estimates at 1, 3, 6, and 12 months after surgery, at no cost. Just as short estimates of survival help justify palliative therapy or less-invasive approaches to stabilization, more favorable survival estimates at 6 or 12 months are used to justify more durable, complicated, and expensive reconstructive options.
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http://dx.doi.org/10.1007/s11999-016-5187-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339146PMC
April 2017

What questionnaires to use when measuring quality of life in sacral tumor patients: the updated sacral tumor survey.

Spine J 2017 05 14;17(5):636-644. Epub 2016 Nov 14.

Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, Room 3.946, Yawkey Building, 55 Fruit St, Boston, MA 02114, USA.

Background Context: Patient-reported outcomes are becoming increasingly important when investigating results of patient and disease management. In sacral tumor, the symptoms of patients can vary substantially; therefore, no single questionnaire can adequately account for the full spectrum of symptoms and disability.

Purpose: The purpose of this study is to analyze redundancy within the current sacral tumor survey and make a recommendation for an updated version based on the results and patient and expert opinions.

Study Design/setting: A survey study from a tertiary care orthopedic oncology referral center was used.

Patient Sample: The patient sample included 70 patients with sacral tumors (78% chordoma).

Outcome Measures: The following 10 questionnaires included in the current sacral tumor survey were evaluated: the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Item short form, PROMIS Pain Intensity short form, PROMIS Pain Interference short form, PROMIS Neuro-QOL v1.0 Lower Extremity Function short form, PROMIS v1.0 Anxiety short form, the PROMIS v1.0 Depression short form, the International Continence Society Male short form, the Modified Obstruction-Defecation Syndrome questionnaire, the PROMIS Sexual Function Profile v1.0, and the Stoma Quality of Life tool.

Methods: We performed an exploratory factor analysis to calculate the possible underlying latent traits. Spearman rank correlation coefficients were used to measure to what extent the questionnaires converged. We hypothesized the existence of six domains based on current literature: mental health, physical health, pain, gastrointestinal symptoms, sexual function, and urinary incontinence. To assess content validity, we surveyed 32 patients, 9 orthopedic oncologists, 1 medical oncologist, 1 radiation oncologist, and 1 orthopedic oncology nurse practitioner with experience in treating sacral tumor patients on the relevance of the domains.

Results: Reliability as measured by Cronbach alpha ranged from 0.65 to 0.96. Coverage measured by floor and ceiling effects ranged from 0% to 52% and from 0% to 30%, respectively. Explanatory factor analysis identified three traits to which the questionnaires that were expected to measure a similar construct correlated the most: mental health, physical function, and pain. Content validity index demonstrated low disagreement among patients (range: 0.10-0.18) and high agreement among physicians (range: 0.91-1.0) on the relevance of the proposed domains. Social health was identified by 50% of the commenting patients as an important yet missing domain.

Conclusions: The current sacral tumor survey is incomplete and time-consuming, and not all surveys are appropriate for the sacral tumor population. Our recommended survey contains less than half the questions and includes the newly recognized social health domain.
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http://dx.doi.org/10.1016/j.spinee.2016.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539909PMC
May 2017

Successful treatment of two cases of classical Hodgkin lymphoma-associated hemophagocytic lymphohistiocyosis with R-CEPP.

Leuk Lymphoma 2017 02 24;58(2):478-481. Epub 2016 Jun 24.

b Division of Hematology, Oncology and Transplantation, Department of Medicine , University of Minnesota , Minneapolis , MN , USA.

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http://dx.doi.org/10.1080/10428194.2016.1193857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549944PMC
February 2017

I am here.

Authors:
Patrick J Boland

Minn Med 2016 May-Jun;99(3):24-5

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July 2016

Genomic aberrations frequently alter chromatin regulatory genes in chordoma.

Genes Chromosomes Cancer 2016 07 9;55(7):591-600. Epub 2016 May 9.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.

Chordoma is a rare primary bone neoplasm that is resistant to standard chemotherapies. Despite aggressive surgical management, local recurrence and metastasis is not uncommon. To identify the specific genetic aberrations that play key roles in chordoma pathogenesis, we utilized a genome-wide high-resolution SNP-array and next generation sequencing (NGS)-based molecular profiling platform to study 24 patient samples with typical histopathologic features of chordoma. Matching normal tissues were available for 16 samples. SNP-array analysis revealed nonrandom copy number losses across the genome, frequently involving 3, 9p, 1p, 14, 10, and 13. In contrast, copy number gain is uncommon in chordomas. Two minimum deleted regions were observed on 3p within a ∼8 Mb segment at 3p21.1-p21.31, which overlaps SETD2, BAP1 and PBRM1. The minimum deleted region on 9p was mapped to CDKN2A locus at 9p21.3, and homozygous deletion of CDKN2A was detected in 5/22 chordomas (∼23%). NGS-based molecular profiling demonstrated an extremely low level of mutation rate in chordomas, with an average of 0.5 mutations per sample for the 16 cases with matched normal. When the mutated genes were grouped based on molecular functions, many of the mutation events (∼40%) were found in chromatin regulatory genes. The combined copy number and mutation profiling revealed that SETD2 is the single gene affected most frequently in chordomas, either by deletion or by mutations. Our study demonstrated that chordoma belongs to the C-class (copy number changes) tumors whose oncogenic signature is non-random multiple copy number losses across the genome and genomic aberrations frequently alter chromatin regulatory genes. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/gcc.22362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031498PMC
July 2016

How Does the Level of Nerve Root Resection in En Bloc Sacrectomy Influence Patient-Reported Outcomes?

Clin Orthop Relat Res 2017 Mar;475(3):607-616

Orthopaedic Oncology Service, Department of Orthopaedic Surgery, Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA.

Background: For patients with sacral tumors, who are well enough for surgery, en bloc resection is the preferred treatment. Survival, postoperative complications, and recurrent rates have been described, but patient-reported outcomes often are not included in these studies.

Questions/purposes: The purposes of this study were (1) to compare patient-reported outcomes after en bloc sacrectomy, based on the level of sacral nerve root resection, in terms of mental health, physical health, bowel function, and sexual function; and (2) to assess differences in terms of mental health, physical health, and pain between patients with and without a colostomy.

Methods: A total of 74 patients, of whom 58 (78%) were diagnosed with chordoma, were surveyed between February 2012 and October 2014. This represented 48% of patients with sacral chordoma who were alive and who had been treated with a transverse sacral resection between June 2000 and August 2013 at three institutions with a minimum followup of 6 months (mean, 59 months; range, 6-255 months). We chose 6 months because we believe that neurologic deficits generally are stable by this point and that patients generally have recovered from the operation by this time. Patients were divided into five groups based on the most caudal nerve root spared: L5 (N = 10), S1 (N = 22), S2 (N = 17), S3 (N = 18), and S4 (N = 7). Only postoperative outcomes were collected using the National institute of Health's Patient Reported Measurement Information System (PROMIS) Global Health survey, PROMIS Pain Interference survey, PROMIS Pain Intensity survey, PROMIS Sexual Function survey, and the Modified Obstruction and Defecation Score survey.

Results: Differences between two adjacent levels were found in terms of mental health, physical health, and sexual function. Patients in whom the S2 nerve roots were spared had a lower mental health score (median = 44, interquartile range [IQR] = 41-51) than patients in whom the S3 nerve roots were spared (median = 53, IQR = 48-56, q = 0.049). Patients in whom the S2 nerve roots were spared had a slightly lower physical health score (median = 42, IQR = 40-51) than patients in whom the S3 nerve roots were spared (median = 47, IQR = 45-54, q = 0.043). Patients in whom the S1 roots were spared (median = 1.0, range = 1.0-1.0) had a lower orgasm score than patients in whom the S2 nerve roots were spared (median = 3, range = 2-5, q = 0.027). No differences in terms of mental health, physical health, or pain were found between the colostomy group and the no colostomy group.

Conclusions: The combination of our findings can be used to further educate patients and discuss expectations. In an operative setting, these data can be considered when deciding to place a colostomy.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1007/s11999-016-4794-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289168PMC
March 2017

Conservative surgery in the treatment of giant cell tumor of the sacrum: 35 years' experience.

J Neurosurg Spine 2016 Feb 30;24(2):228-240. Epub 2015 Oct 30.

Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center.

OBJECT There is no consensus regarding the appropriate treatment of sacral giant cell tumor (GCT). There are 3 main management problems: tumor control, neurological loss, and pelvic instability. The objective of this study was to examine oncological, neurological, and structural outcomes of sacral GCT after intralesional excision and local intraoperative adjunctive treatment. METHODS The authors retrospectively reviewed the records of 24 patients with sacral GCT who underwent conservative surgery (intralesional resection/curettage) at Memorial Sloan Kettering Cancer Center from 1973 through 2012. They analyzed patient demographic data, tumor characteristics, and operative techniques, and examined possible correlations with postoperative functional outcomes, complications, recurrence, and mortality. RESULTS There were 7 local recurrences (30%) and 3 distant recurrences (13%). Three of 24 patients (12.5%) had significant neurological loss after treatment-specifically, severe bowel and/or bladder dysfunction, but all regained function within 1-4 years. Larger tumor size (> 320 cm) was associated with greater postoperative neurological loss. Radiation therapy and preoperative embolization were associated with prolonged disease-free survival. There were no local recurrences among the 11 patients who were treated with both modalities. Based on radiographic and clinical assessment, spinopelvic stability was present in 23 of 24 patients at final follow-up. CONCLUSIONS High local and distant recurrence rates associated with sacral GCT suggest the need for careful local and systemic follow-up in managing these patients. Intraoperative preservation of sacral roots was associated with better pain relief, improvement in ambulatory function, and retention of bowel/bladder function in most patients. Fusion and instrumentation of the sacroiliac joint successfully achieved spinopelvic stability in cases deemed clinically unstable. Despite improvement in the management of sacral GCT over 35 years, a need for novel therapies remains. The strategy of combining radiotherapy and embolization merits further study.
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http://dx.doi.org/10.3171/2015.4.SPINE13215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161744PMC
February 2016

Revision Distal Femoral Arthroplasty With the Compress(®) Prosthesis Has a Low Rate of Mechanical Failure at 10 Years.

Clin Orthop Relat Res 2016 Feb 22;474(2):528-36. Epub 2015 Sep 22.

Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Background: Patients with failed distal femoral megaprostheses often have bone loss that limits reconstructive options and contributes to the high failure rate of revision surgery. The Compress(®) Compliant Pre-stress (CPS) implant can reconstruct the femur even when there is little remaining bone. It differs from traditional stemmed prostheses because it requires only 4 to 8 cm of residual bone for fixation. Given the poor long-term results of stemmed revision constructs, we sought to determine the failure rate and functional outcomes of the CPS implant in revision surgery.

Questions/purposes: (1) What is the cumulative incidence of mechanical and other types of implant failure when used to revise failed distal femoral arthroplasties placed after oncologic resection? (2) What complications are characteristic of this prosthesis? (3) What function do patients achieve after receiving this prosthesis?

Methods: We retrospectively reviewed 27 patients who experienced failure of a distal femoral prosthesis and were revised to a CPS implant from April 2000 to February 2013. Indications for use included a minimum 2.5 mm cortical thickness of the remaining proximal femur, no prior radiation, life expectancy > 10 years, and compliance with protected weightbearing for 3 months. The cumulative incidence of failure was calculated for both mechanical (loss of compression between the implant anchor plug and spindle) and other failure modes using a competing risk analysis. Failure was defined as removal of the CPS implant. Followup was a minimum of 2 years or until implant removal. Median followup for patients with successful revision arthroplasty was 90 months (range, 24-181 months). Functional outcomes were measured with the Musculoskeletal Tumor Society (MSTS) functional assessment score.

Results: The cumulative incidence of mechanical failure was 11% (95% confidence interval [CI], 4%-33%) at both 5 and 10 years. These failures occurred early at a median of 5 months. The cumulative incidence of other failures was 18% (95% CI, 7%-45%) at 5 and 10 years, all of which were deep infection. Three patients required secondary operations for cortical insufficiency proximal to the anchor plug in bone not spanned by the CPS implant and unrelated to the prosthesis. Median MSTS score was 27 (range, 24-30).

Conclusions: Revision distal femoral replacement arthroplasty after a failed megaprosthesis is often difficult as a result of a lack of adequate bone. Reconstruction with the CPS implant has an 11% failure rate at 10 years. Our results are promising and demonstrate the durable fixation provided by the CPS implant. Further studies to compare the CPS prosthesis and other reconstruction options with respect to survival and functional outcomes are warranted.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1007/s11999-015-4552-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709327PMC
February 2016

Factitious disorder (Munchausen's syndrome) in oncology: case report and literature review.

Psychooncology 2016 06 14;25(6):707-11. Epub 2015 Jul 14.

Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Background: Factitious disorder is where patients repeatedly seek medical care for feigned illnesses in the absence of obvious external rewards; 'Munchausen's syndrome' is the historical name for this disorder.

Method: We report on a case that was presented to a tertiary oncology center as a suspected rare bone cancer.

Results And Conclusions: Psychosocial clinicians working in oncology settings should be aware of the complexities of diagnosing factitious disorder in cancer settings where empathy is prominent and suspicion unusual. Moreover, comorbidity can cloud the diagnosis (in this case substance abuse), and, even when accurately diagnosed, there are no evidence-based management approaches to offer to the patient. What seems to linger most after the patient is discharged, usually in a huff, are strong counter-transference feelings and substantial medical bills. Copyright © 2015 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pon.3906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481998PMC
June 2016

How Does the Level of Sacral Resection for Primary Malignant Bone Tumors Affect Physical and Mental Health, Pain, Mobility, Incontinence, and Sexual Function?

Clin Orthop Relat Res 2016 Mar;474(3):687-96

Department of Orthopaedic Surgery, Massachusetts General Hospital, Yawkey 3A, 55 Fruit Street, Boston, MA, 02114, USA.

Background: 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.

Questions/purposes: 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.

Methods: 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.

Results: 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.

Conclusions: 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 Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1007/s11999-015-4361-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746195PMC
March 2016

Ewing sarcoma in adults treated with modern radiotherapy techniques.

Radiother Oncol 2014 Nov 26;113(2):248-53. Epub 2014 Nov 26.

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

Background And Purpose: To evaluate local control and survival outcomes in adults with Ewing sarcoma (ES) treated with radiotherapy (RT).

Material And Methods: Retrospective review of all 109 patients age ⩾18 treated for ES with RT to the primary site at Memorial Sloan Kettering Cancer Center between 1990 and 2011. RT was used as the definitive local control modality in 44% of patients, preoperatively for 6%, and postoperatively for 50%.

Results: Median age at diagnosis was 27years (range, 18-67). The 5-year local failure (LF) was 18%. Differences in LF were not identified when evaluated by modality of local control (RT versus combined surgery and RT), RT dose, fractionation, and RT technique. However, margin status at time of resection significantly predicted LF. The 5-year event-free survival and overall survival rates were 44% and 66% for patients with localized disease, compared with 16% and 26% for metastatic disease (p=0.0005 and 0.0002). Tumor size, histopathologic response to chemotherapy, and treatment on or according to a protocol were also significantly associated with survival.

Conclusions: This series of adults treated with modern chemotherapy and RT had prognostic factors and outcomes similar to adolescents with ES. All adults with ES should be treated with an aggressive, multidisciplinary approach.
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http://dx.doi.org/10.1016/j.radonc.2014.11.023DOI Listing
November 2014

Insufficiency fractures of the sacrum following stereotactic body radiotherapy for sacral tumors.

J Radiosurg SBRT 2014 ;3(1):59-65

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.

Introduction: There is little data on sacral insufficiency fracture(SIF) incidence following pelvic radiotherapy, with existing studies based on conventional fractionation. Stereotactic body radiotherapy (SBRT), characterized by dose escalation with hypofractionation, may pose even greater risks to sacral integrity. This study aims to define SIF incidence and risk factors following SBRT.

Methods: Records of 43 consecutive patients who underwent sacral SBRT from September 2005-May 2009 were reviewed. Baseline patient information (age, gender, menopausal status, body mass index, use of bone-thinning agents, presence of osteoporosis), tumor characteristics (histology, lesion appearance and extent) and treatment parameters (dose/fractionation, prior radiation/surgery) were documented. Primary end-point was development of new fractures or progression of pre-existing fractures. Secondary end-points included pain scores, analgesic use, functional ability, and local tumor control.

Results: Median follow-up was 17months. Common histologies included sarcoma, renal cell, and prostate carcinoma; 47% of lesions were lytic, 37% sclerotic and the remainder mixed. Doses ranged from 18-24Gy/1fraction to 30Gy/5fractions with 45% receiving single fractions.14% had prior radiation (median dose: 30Gy/10fractions).Five patients developed SIF. In four, fractures occurred in the context of controlled local disease. Median time to SIF was 8.2months. Symptoms varied from minimal pain requiring no intervention to severe pain impacting on function. Two patients underwent sacroplasty due to intractable pain, with both obtaining good analgesia. Low event numbers precluded meaningful univariate/multivariate analyses. One-year local tumor control rates were excellent (91.7%).

Conclusion: In this study, actuarial SIF incidence at one year was 8.2%, suggesting that SIF risk from sacral SBRT is low. However, larger prospective studies with longer follow-up are needed. In addition, novel therapies such as sacroplasty need further study to determine safety, efficacy and indications for use.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725331PMC
January 2014

Preliminary results of high-dose single-fraction radiotherapy for the management of chordomas of the spine and sacrum.

Neurosurgery 2013 Oct;73(4):673-80; discussion 680

Departments of †Radiation Oncology, ‡Neurosurgery, §Medical Physics, and ¶Orthopedics, Memorial Sloan-Kettering Cancer Center, New York, New York; ‖Department of Neurologic Surgery, Weill Cornell Medical College, New York, New York; #Departments of Medicine, Pediatrics, and Orthopedics, Mount Sinai School of Medicine, New York, New York.

Background: En bloc wide-margin excision significantly decreases the risk of chordoma recurrence. However, a wide surgical margin cannot be obtained in many chordomas because they arise primarily in the sacrum, clivus, and mobile spine. Furthermore, these tumors have shown resistance to fractionated photon radiation at conventional doses and numerous chemotherapies.

Objective: To analyze the outcomes of single-fraction stereotactic radiosurgery (SRS) in the treatment of chordomas of the mobile spine and sacrum.

Methods: Twenty-four patients with chordoma of the sacrum and mobile spine were treated with high-dose single-fraction SRS (median dose, 2400 cGy). Twenty-one primary and 3 metastatic tumors were treated. Seven patients were treated for postoperative tumor recurrence. In 7 patients, SRS was administered as planned adjuvant therapy, and in 13 patients, SRS was administered as neoadjuvant therapy. All patients had serial magnetic resonance imaging follow-up.

Results: The overall median follow-up was 24 months. Of the 24 patients, 23 (95%) demonstrated stable or reduced tumor burden based on serial magnetic resonance imaging. One patient had radiographic progression of tumor 11 months after SRS. Only 6 of 13 patients who underwent neoadjuvant SRS proceeded to surgery. This decision was based on the lack of radiographic progression and the patient's preference. Complications were limited to 1 patient in whom sciatic neuropathy developed and 1 with vocal cord paralysis.

Conclusion: High-dose single-fraction SRS provides good tumor control with low treatment-related morbidity. Additional follow-up is required to determine the long-term recurrence risk.
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October 2013

Comparison between Constrained and Semiconstrained Knee Allograft-Prosthesis Composite Reconstructions.

Sarcoma 2013 14;2013:489652. Epub 2013 Feb 14.

Department of Surgery, Orthopaedic Surgery Service, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, Cornell University, New York, NY, USA ; Institute of Orthopedics "Carlos E. Ottolenghi," Italian Hospital of Buenos Aires, Buenos Aires, Argentina.

Allograft-prosthesis composite (APC) can restore capsular and ligamentous tissues of the knee sacrificed in a tumor extirpation. We asked if performing APC would restore knee stability and allow the use of nonconstrained arthroplasty while preventing aseptic loosening. We retrospectively compared 50 knee APCs performed with non-constrained revision knee prosthesis (Group 1) with 36 matched APCs performed with a constrained prosthesis (Group 2). In Group 1, the survival rate was 69% at five and 62% at ten years. Sixteen reconstructions were removed due to complications: eight deep infections, three fractures, two instabilities, one aseptic loosening, one local recurrence, and one nonunion. In Group 2, the survival rate was 80% at five and 53% at ten years. Nine reconstructions were removed: 3 due to deep infections, 3 to fractures, and 3 to aseptic loosening. In both groups, we observed more allograft fractures when the prosthetic stem does not bypass the host-donor osteotomy (P > 0.05). Both groups had mainly good or excellent MSTS functional results. Survival rate and functional scores and aseptic loosening were similar in both groups. A rotating-hinge APC is recommended when host-donor soft tissue reconstruction fails to restore knee instability. The use of a short prosthetic stem has a statistical relationship with APC fractures.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586499PMC
March 2013