What Are the Complications, Function, and Survival of Tumor-devitalized Autografts Used in Patients With Limb-sparing Surgery for Bone and Soft Tissue Tumors? A Japanese Musculoskeletal Oncology Group Multi-institutional Study.

BACKGROUND: Tumor-devitalized autografts treated with deep freezing, pasteurization, and irradiation are biological reconstruction methods after tumor excision for aggressive or malignant bone or soft tissue tumors that involve a major long bone. Tumor-devitalized autografts do not require a bone bank, they carry no risk of viral or bacterial disease transmission, they are associated with a smaller immunologic response, and they have a better shape and size match to the site in which they are implanted. However, they are associated with disadvantages as well; it is not possible to assess margins and tumor necrosis, the devitalized bone is not normal and has limited healing potential, and the biomechanical strength is decreased owing to processing and tumor-related bone loss. Because this technique is not used in many countries, there are few reports on the results of this procedure such as complications, graft survival, and limb function. QUESTIONS/PURPOSES: (1) What was the rate of complications such as fracture, nonunion, infection, or recurrence in a tumor-devitalized autograft treated with deep freezing, pasteurization, and irradiation, and what factors were associated with the complication? (2) What were the 5-year and 10-year grafted bone survival (free from graft bone removal) of the three methods used to devitalize a tumor-containing autograft, and what factors were associated with grafted bone survival? (3) What was the proportion of patients with union of the tumor-devitalized autograft and what factors were associated with union of the graft-host bone junction? (4) What was the limb function after the tumor-devitalized autograft, and what factors were related to favorable limb function? METHODS: This was a retrospective, multicenter, observational study that included data from 26 tertiary sarcoma centers affiliated with the Japanese Musculoskeletal Oncology Group. From January 1993 to December 2018, 494 patients with benign or malignant tumors of the long bones were treated with tumor-devitalized autografts (using deep freezing, pasteurization, or irradiation techniques). Patients who were treated with intercalary or composite (an osteoarticular autograft with a total joint arthroplasty) tumor-devitalized autografts and followed for at least 2 years were considered eligible for inclusion. Accordingly, 7% (37 of 494) of the patients were excluded because they died within 2 years; in 19% (96), an osteoarticular graft was used, and another 10% (51) were lost to follow-up or had incomplete datasets. We did not collect information on those who died or were lost to follow-up. Considering this, 63% of the patients (310 of 494) were included in the analysis. The median follow-up was 92 months (range 24 to 348 months), the median age was 27 years (range 4 to 84), and 48% (148 of 310) were female; freezing was performed for 47% (147) of patients, pasteurization for 29% (89), and irradiation for 24% (74). The primary endpoints of this study were the cumulative incidence rate of complications and the cumulative survival of grafted bone, assessed by the Kaplan-Meier method. We used the classification of complications and graft failures proposed by the International Society of Limb Salvage. Factors relating to complications and grafted autograft removal were analyzed. The secondary endpoints were the proportion of bony union and better limb function, evaluated by the Musculoskeletal Tumor Society score. Factors relating to bony union and limb function were also analyzed. Data were investigated in each center by a record review and transferred to Kanazawa University. RESULTS: The cumulative incidence rate of any complication was 42% at 5 years and 51% at 10 years. The most frequent complications were nonunion in 36 patients and infection in 34 patients. Long resection (≥ 15 cm) was associated with an increased risk of any complication based on the multivariate analyses (RR 1.8 [95% CI 1.3 to 2.5]; p < 0.01). There was no difference in the rate of complications among the three devitalizing methods. The cumulative graft survival rates were 87% at 5 years and 81% at 10 years. After controlling for potential confounding variables including sex, resection length, reconstruction type, procedure type, and chemotherapy, we found that long resection (≥ 15 cm) and composite reconstruction were associated with an increased risk of grafted autograft removal (RR 2.5 [95% CI 1.4 to 4.5]; p < 0.01 and RR 2.3 [95% CI 1.3 to 4.1]; p < 0.01). The pedicle freezing procedure showed better graft survival than the extracorporeal devitalizing procedures (94% versus 85% in 5 years; RR 3.1 [95% CI 1.1 to 9.0]; p = 0.03). No difference was observed in graft survival among the three devitalizing methods. Further, 78% (156 of 200 patients) of patients in the intercalary group and 87% (39 of 45 patients) of those in the composite group achieved primary union within 2 years. Male sex and the use of nonvascularized grafts were associated with an increased risk of nonunion (RR 2.8 [95% CI 1.3 to 6.1]; p < 0.01 and 0.28 [95% CI 0.1 to 1.0]; p = 0.04, respectively) in the intercalary group after controlling for confounding variables, including sex, site, chemotherapy, resection length, graft type, operation time, and fixation type. The median Musculoskeletal Tumor Society score was 83% (range 12% to 100%). After controlling for confounding variables including age, site, resection length, event occurrence, and graft removal, age younger than 40 years (RR 2.0 [95% CI 1.1 to 3.7]; p = 0.03), tibia (RR 6.9 [95% CI 2.7 to 17.5]; p < 0.01), femur (RR 4.8 [95% CI 1.9 to 11.7]; p < 0.01), no event (RR 2.2 [95% CI 1.1 to 4.5]; p = 0.03), and no graft removal (RR 2.9 [95% CI 1.2 to 7.3]; p = 0.03) were associated with an increased limb function. The composite graft was associated with decreased limb function (RR 0.4 [95% CI 0.2 to 0.7]; p < 0.01). CONCLUSION: This multicenter study revealed that frozen, irradiated, and pasteurized tumor-bearing autografts had similar rates of complications and graft survival and all resulted in similar limb function. The recurrence rate was 10%; however, no tumor recurred with the devitalized autograft. The pedicle freezing procedure reduces the osteotomy site, which may contribute to better graft survival. Furthermore, tumor-devitalized autografts had reasonable survival and favorable limb function, which are comparable to findings reported for bone allografts. Overall, tumor-devitalized autografts are a useful option for biological reconstruction and are suitable for osteoblastic tumors or osteolytic tumors without severe loss of mechanical bone strength. Tumor-devitalized autografts could be considered when obtaining allografts is difficult and when a patient is unwilling to have a tumor prosthesis and allograft for various reasons such as cost or socioreligious reasons. LEVEL OF EVIDENCE: Level III, therapeutic study.

Hip Transposition Can Provide Early Walking Function After Periacetabular Tumor Resection: A Multicenter Study.

BACKGROUND: Reconstruction after periacetabular bone tumor resection involves important tradeoffs; large bone grafts or endoprostheses are reported to offer fair walking function in general but can be technically demanding and carry a high risk of severe complications. Conversely, hip transposition avoids implant-related risks, but stability and functional return may be less consistent. Fewer studies are available on hip transposition, which is also appealing in more resource-constrained environments, and little is known about the time course from surgery to functional return after hip transposition. QUESTIONS/PURPOSES: (1) What is the time course of recovery of walking function after hip transposition, especially in the first 6 months? (2) What factors are associated with a greater likelihood of early functional recovery? (3) Is early (2-month) functional recovery associated with a greater likelihood of walking ability and higher Musculoskeletal Tumor Society (MSTS) scores? METHODS: Between 2009 and 2019, six tertiary care centers in Japan treated 48 patients with internal hemipelvectomy for malignant tumors. During that time, the preferred reconstructive approach was hip transposition, and 92% (44 of 48) of our patients were treated with this procedure. Among them, 86% (38 of 44) had follow-up of at least 6 months, had no local recurrence during that time, and were included in our retrospective study. We chose 6 months as the minimum follow-up duration because the endpoints in this study pertained to early recovery rather than reconstructive durability. Hip transposition involved moving the proximal end of the femur (femoral head, resection end of the trochanteric area, and spacers such as prostheses) upward to the underside of the resected ilium or the lateral side of the sacrum if sacroiliac joint resection was performed. The end of the proximal femur was stabilized to the remaining ilium or sacrum using polyethylene tape, polyethylene terephthalate mesh, an iliotibial tract graft, or an external fixator, according to the surgeon's preference. The median age at surgery was 46 years (range 9 to 76 years), there were 23 women and 15 men, and the median follow-up duration was 17 months (range 6 to 110 months). The postoperative time course of functional recovery was assessed with a record review, the timing of functional milestones was identified (wheelchair, walker, bilateral crutches, single crutch or cane, and walking without an aid), and the MSTS score at the final follow-up was assessed. Additionally, demographic and surgical factors were reviewed, and their association with short-term functional recovery and the final functional outcome was analyzed. RESULTS: Patients started using a walker at median postoperative day (POD) 20 (IQR 14 to 36) and with bilateral crutches at median POD 35 (IQR 20 to 57). At POD 60, which was the approximate median date of discharge, 76% (29 of 38) of patients were able to walk using bilateral crutches (the early recovery group) and 24% (nine of 38) of patients were not able to do so (the delayed recovery group). No baseline factors were different between the two groups. The early recovery group had a higher median MSTS score than the delayed recovery group: 57% (range 17% to 90%) versus 45% (13% to 57%) (p = 0.047). Moreover, more patients acquired better function (a single crutch or cane or more) in the early recovery group, with a median of 5 months (95% CI 4 to 11) than did those in the delayed recovery group (median not reached) (p = 0.0006). The HR was 15.2 (95% CI 2.5 to 93). Forty-two percent (16 of 38) underwent additional surgery for wound management. CONCLUSION: It took patients a fair amount of time to recover walking function after hip transposition, and patients who could not walk on bilateral crutches at POD 60 seemed less likely to regain walking function and were likely to have lower MSTS scores thereafter. Wound-related complications were frequent. This method may be a realistic alternative for younger patients who have the strength for a long rehabilitation period or those who want to minimize prosthesis-related complications. Future studies with more patients are necessary to understand the risk factors associated with delayed recovery.Level of Evidence Level III, therapeutic study.

Complications and Functional Outcome Differences in Carbon Ion Radiotherapy and Surgery for Malignant Bone Tumors of the Pelvis: A Multicenter, Cohort Study.

BACKGROUND: Carbon ion radiotherapy (CIRT) is an evolving treatment option for malignant pelvic tumors in patients with poor surgical indications. However, the difference in complications and functional outcomes between CIRT and surgery is poorly understood. This study compares the complications and functional outcomes of CIRT and surgery to facilitate treatment selection. METHODS: A total of 28 patients who underwent CIRT for pelvic bone tumors while theoretically meeting the surgical resection criteria were included. Sixty-nine patients who underwent surgery for pelvic bone tumors were included as controls. Major complication rates and functional outcomes (ambulatory, pain, urination, constipation) were evaluated and compared at several time points (pretreatment, discharge, and final follow-up) between the groups. RESULTS: Early (within 90 days) major complications were not observed in the CIRT group but occurred in 30% of the surgery group, which was statistically significant (P < 0.001). In contrast, late (after 90 days) major complications occurred more often in the CIRT group than in the surgery group (18% and 4%, respectively; P = 0.042). From pretreatment until discharge, all functional outcomes in the surgery group deteriorated (P < 0.001 for all) but did not change in the CIRT group (P = 0.77-1.00). At the final follow-up, all functional outcomes showed no significant intergroup difference (P = 0.28-0.92) due to the recovery trend in the surgery group and the deterioration trend in the CIRT group. CONCLUSIONS: Compared with surgery, CIRT may have favorable safety and stable functional outcomes in the short-term but more late complications. Mid-term functional outcomes were similar between the groups.

Image-guided core needle biopsy for musculoskeletal lesions.

BACKGROUND: Image-guided percutaneous core needle biopsy (CNB) has been an important diagnostic procedure for musculoskeletal lesions. Here we surveyed the variety of diagnostic strategies available and assessed the clinical usefulness and limitations of image-guided CNB carried out by a multidisciplinary team comprising specialists in various fields. METHODS: We conducted a retrospective study of 284 image-guided CNBs among 1899 consecutive biopsy procedures carried out at our institution for musculoskeletal tumorous conditions, focusing on their effectiveness including diagnostic accuracy and utility for classification of specimens according to malignant potential and histological subtype as well as their correlation with biopsy routes. RESULTS: Among the 284 studied biopsies, 252 (88.7%) were considered clinically "effective". The sensitivity for detection of malignancy was 94.0% (110/117) and the specificity was 95.3% (41/43). The diagnostic accuracy for detection of malignancy was 94.4% (151/160) and that for histological subtype was 92.3% (48/52). The clinical effectiveness of the procedure was correlated with the complexity of the biopsy route (P = 0.015); the trans-pedicular, trans-retroperitoneal and trans-sciatic foramen approaches tended to yield ineffective results. Repeat biopsy did not have a significant impact on the effectiveness of image-guided CNB (P = 0.536). CONCLUSIONS: The diagnostic accuracy rates of image-guided CNB performed at multidisciplinary sarcoma units were usable even for patients who have variety of diagnostic biopsy procedures. It is important to establish and implement diagnostic strategies based on an understanding that complicated routes, especially for spine and pelvic lesions, may be associated with ineffectiveness and/or complications.

An aggressive nodular fasciitis lesion protruding from the palm (USP6 gene fusion helps differentiate from sarcomas): A case report.

Nodular fasciitis is a mesenchymal lesion, which has been viewed as a reactive process. The MYH9-USP6 fusion gene was recently detected in nodular fasciitis, and nodular fasciitis is now considered to be a self-limiting neoplastic process. Recently, a case of nodular fasciitis that recurred a number of times and metastasized to soft tissues was reported, and the features of aggressive cases of nodular fasciitis are currently under investigation. Here, a case of locally aggressive nodular fasciitis is presented, in which the lesion grew rapidly and caused ulnar nerve palsy. The lesion was locally controlled via marginal excision, and no metastasis was identified at 24 months post-operation. Histologically, the lesion was consistent with nodular fasciitis, and the detection of the MYH9-USP6 fusion gene supported the diagnosis. Although most nodular fasciitis lesions are benign, some may be locally aggressive or even metastasize. In the case outlined in the present study, marginal excision was sufficient to locally control the lesion.

Osteosarcoma arising from acetabulum extended to femoral head through round ligament: a case report.

A skip metastasis was defined as a solitary separate focus of osteosarcoma occurring synchronously with a primary osteosarcoma in the absence of anatomic extension. The progression of skip metastasis is considered less likely because the articular cartilage acts as a barrier, so there have been few reports on progression of the extremity bone tumor across a joint. In our case report, the acetabular osteosarcoma progressed to the femoral head through the ligament of the femoral head. From the findings of magnetic resonance imaging and resected specimen and tissue specimen, we considered that the tumor progressed between ligament and synovial tissue covering the ligament, and not passing through the inside of the ligament. This case suggested a possibility that the tumor might progress through the synovium around the ligament of femoral head in the cases of osteosarcoma arising from the proximal femur and acetabulum.

Giant Cell Tumor With Atypical Imaging Implying Osteosarcoma.

Giant cell tumor (GCT) of bone is benign and typically shows osteolytic changes on x-ray, whereas osteosarcoma is malignant and generally shows osteolytic and osteoblastic mixed images. We experienced a rare case of GCT with atypical radiological findings. The tumor found in the right knee of a 15-year-old girl comprised a wide range of osteoblastic and osteolytic lesion in medial femur. Technetium uptake, however, was detected only in osteoblastic part, and immunohistochemical staining of biopsy showed diffusely positive for antihistone G34W and almost negative for Ki-67. These results strongly suggest the tumor was GCT.

Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan.

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

Risk factor for wound complications following wide resection of soft tissue sarcoma in the adductor compartment of the thigh.

BACKGROUND: The purpose of this study was to investigate deep-seated soft tissue sarcoma (STS) occurring in the adductor compartment of the thigh that underwent wide resection and to clarify the high-risk group for wound complications. PATIENTS AND METHODS: From 2000 to 2017, we reviewed 104 cases of deep-seated STS occurring in the adductor compartment of the thigh that were treated at four specialized facilities with expertise in sarcoma treatment. RESULTS: Wound complications occurred in 40 cases (38.5%), of which 23 cases (22.1%) were cases with major wound complications (MWC). In univariate analysis, BMI (P < 0.01), maximum tumor diameter (P < 0.01), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P < 0.01) were significantly associated with wound complications. In multivariate analysis, the associated parameters were BMI (P < 0.01), maximum tumor diameter (P = 0.02), and intraoperative intervention to the femoral artery and vein (P = 0.01). When limited to cases with MWC, univariate analysis showed that maximum tumor diameter (P < 0.01), diabetes mellitus (P = 0.03), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P = 0.02) were significantly associated parameters. In multivariate analysis, maximum tumor diameter (P = 0.02) and amount of intraoperative bleeding (P = 0.04) were associated parameters. CONCLUSIONS: For patients with risk factors for wound complications, control of bleeding are crucial when resecting deep-seated STS in the adductor compartment of the thigh. In cases with large tumors, surgeons should be especially cautious of cases requiring interventions that surround the femoral artery and vein in order to attain an appropriate surgical margin.

G-CSF-producing Undifferentiated Pleomorphic Sarcoma Adjacent to the Ascending Colon and in the Right Iliopsoas Muscle: A Case Report and Review of the Literature.

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on 18F-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.

Is immunohistochemical staining for ß-catenin the definitive pathological diagnostic tool for desmoid-type fibromatosis? A multi-institutional study.

Immunohistochemical staining with anti-ß-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatoses (DFs). In recent years, specific gene mutation (CTNNB1) analysis has also been reported to be useful for diagnosis of DF; however, the association between CTNNB1 mutation status and immunohistochemical staining pattern of ß-catenin is rarely reported. The purposes of this study are to clarify the relationship of the staining pattern of ß-catenin with the CTNNB1 mutation status and various clinical variables, and to investigate the significance of immunohistochemical staining of ß-catenin in cases diagnosed as DF. Between 1997 and 2017, 104 cases diagnosed as DF from 6 institutions in Japan were enrolled in this study: Nagoya University, National Cancer Center Hospital, Niigata University, Okayama University, Kyushu University, and Cancer Institute Hospital. For all cases, immunohistochemical staining of ß-catenin and gene mutation analysis of CTNNB1 were performed. Of 104 cases, 87 (84%) showed nuclear staining of ß-catenin, and 95 (91%) showed positive staining in the cytoplasm. The proportion of cases showing strong nuclear staining of ß-catenin was significantly higher in the cases with S45F than in those with T41A or wild type. The proportion of cases stained strongly in the cytoplasm rather than in the nucleus was significantly higher in the group of T41A than that of S45F or wild type. Among 17 cases in which nuclear immunostaining was absent, CTNNB1 mutation was observed in 5 cases (29.4%). There were unignorable cases of DF with negative ß-catenin immunostaining despite a definitive clinical and pathological diagnosis of DF and/or positive CTNNB1 mutation.

Giant cell tumor of the distal femur: Outcome beyond 20 years of follow-up after curettage with polymethylmethacrylate.

BACKGROUND: Polymethymethacrylate (PMMA) is often used to reconstruct defects after curettage of Giant Cell Tumors (GCT). While GCTs usually originate in the epiphysis, the use of PMMA in distal femoral lesions may induce the risk of degenerative osteoarthritis (OA). We investigated the limb function of patients after curettage with PMMA beyond 20 years of follow-up. METHODS: Patients with more than 20 years of follow-up who underwent curettage with PMMA for distal femoral GCTs were observed. We retrospectively investigated the radiographic assessment of OA and functional assessment of the limb. The Kellgren and Lawrence (KL) grading system was used for radiographic evaluation. RESULTS: Five patients were included in this study. The mean age was 33 years, and the mean period from application of PMMA to final follow-up observation was 28.1 years. Four lesions were primary, and one lesion was recurrent. There were no patients with postoperative recurrence. There were no OA changes in preoperative radiographs. The shortest mean distance from PMMA to the articular cartilage was 4.6 mm on radiographs immediately after surgery. On radiographs at final follow-up observation, the KL grading were as follows: grade 1, 2 patients; grade 2, 1 patient; grade 3, 2 patients. All patients were able to independently ambulate without a crutch, and there was not enough pain to require nonsteroidal anti-inflammatory drugs. The mean flexion of the knee joint was 116°. CONCLUSIONS: Although PMMA used for distal femoral GCTs exhibited OA changes beyond a 20 year follow-up period, there were no cases requiring artificial joints, and the affected limbs demonstrated good function.

Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes.

BACKGROUND: Chordomas are very rare primary malignant bone tumors that arise commonly from the sacrum (50-60%) and clivus (25-35%). Chordomas have a high rate of recurrence. The authors confirmed a unique histologic infiltration pattern of chordomas that resembles a skip-metastatic lesion in normal tissue around tumor, which they named "micro-skip metastasis." This study aimed to examine the correlations between the clinicopathologic features of chordomas, including micro-skip metastasis, and the clinical outcomes, including overall survival, local recurrence-free survival, and distant metastasis-free survival. METHODS: The study analyzed histopathologic and clinical data from patients with sacral chordomas who underwent en bloc resection from July 1991 through July 2014. Cases with a minimum follow-up period shorter than 20 months after resection were excluded. Kaplan-Meier survival analyses with log-rank tests were performed for overall survival, metastasis-free survival, and recurrence-free survival. RESULTS: The study retrospectively reviewed 40 patients. The mean follow-up period was 98.2 months (range 22-297 months). The local recurrence rate was 41.3%. Micro-skip metastases, observed in 17 patients (42.5%), were associated with a significantly increased risk of local recurrence (p = 0.023) but not with overall survival or distant metastasis-free survival. Poorer overall survival was associated with histologic vascular invasion (p = 0.030) and a greater maximum tumor diameter (p = 0.050). CONCLUSIONS: The presence of micro-skip metastasis was associated with a higher rate of local recurrence. The maximum tumor diameter and the presence of histologic vascular invasion were associated with poorer overall survival.

Multicentric giant cell tumor of bone: Case series of 4 patients.

BACKGROUND: We aimed to retrospectively investigate patients with multicentric giant cell tumor (MCGCT) who were treated at our hospital and to clarify their clinical features, treatment policy, and follow-up method. METHODS: Four patients with two or more giant cell tumor (GCT) that occurred in the same patient were treated at our institution between 1978 and 2015. These patients were evaluated for the following: frequency, age of onset, number and site of occurrence, time to occurrence of the next lesion, treatment, recurrence, malignant transformation, metastasis, and oncological outcome. RESULTS: The rate of occurrence was 1.7%. The average age was 25.2 (17-44). The total number of lesions was three in two cases and two in two cases. All four cases had only one lesion during the initial visit. The most frequent site of occurrence was the proximal femur, followed by two lesions that occurred in the metaphysis. The interval between confirmation of the initial lesion and occurrence of the second lesion was in average 12.1 years (0.8-27.0). Initial presentations of lesions were treated by en bloc resection in one case and curettage in three cases. Local recurrences occurred in two cases that underwent curettage. The six lesions that occurred after the initial lesion were treated as follows: en bloc resection in four lesions, curettage and radiation therapy in one, and embolization and radiation therapy in one. Pathologically, no lesions presented malignancy. Pulmonary metastasis occurred in one case. The oncological outcome was NED in three cases and AWD in one case. CONCLUSIONS: No lesions were malignant, and by providing the same treatment as solitary GCT, the oncological outcome was good. It is unnecessary to be concerned of its risks and postoperatively conduct long-term searches for focal lesions across the body.

Can A Multivariate Model for Survival Estimation in Skeletal Metastases (PATHFx) Be Externally Validated Using Japanese Patients?

BACKGROUND: Objective survival estimates are important when treating or studying outcomes in patients with skeletal metastases. One decision-support tool, PATHFx (www.pathfx.org) is designed to predict each patient's postsurgical survival trajectory at 1, 3, 6, and 12 months in patients undergoing stabilization for skeletal metastases. PATHFx has been externally validated in various western centers, but it is unknown whether it may be useful in Asian patient populations. QUESTIONS/PURPOSES: We asked (1) whether the PATHFx models are as predictive in Japanese patients by estimating the area under the receiver operator characteristic curve (AUC); we considered an AUC greater than 0.7 as an adequate predictive value. We also (2) performed decision curve analysis at various times to determine whether and how PATHFx should be used clinically at those times. PATIENTS AND METHODS: A Bayesian model is a statistical method to explore conditional, probabilistic relationships between variables to estimate the likelihood of an outcome using observed data. We applied the PATHFx Bayesian models to an independent dataset containing the records of patients who underwent skeletal stabilization for metastatic bone disease at one of five Japanese referral centers and had a followup longer than 12 months for survivors. Of 270 patients in the database, we excluded nine patients from analysis because their followup was less than 12 months, and finally we included 261 patients in the analysis. Data examined included age at the time of surgery, sex, indication for surgery (impending fracture or completed pathologic fracture), number of bone metastases (solitary or multiple), presence or absence of visceral or lymph node metastases, preoperative hemoglobin concentration, absolute lymphocyte count, and the primary oncologic diagnosis. We performed receiver operating characteristic curve analysis and estimated the AUC as a measure of discriminatory ability. Decision curve analysis was performed to determine if and how the models should be used in the clinical setting. RESULTS: The AUCs for the 1-, 3-, 6-, and 12-month models were 0.77 (95% CI, 0.63-0.86), 0.80 (95% CI, 0.72-0.87), 0.83 (95% CI, 0.77-0.89), and 0.80 (95% CI, 0.75-0.86), respectively. Decision analysis indicated that the models conferred a positive net benefit (above the lines assuming none or all survive at each time) although the CIs of the AUC for 1 month were wide, suggesting that this dataset could not adequately predict 1-month survival. CONCLUSIONS: Our findings show PATHFx is suitable for clinical use in Japan and may be used to guide surgical decision making or as a risk stratification method in support of clinical trials involving Japanese patients at 3, 6, and 12 months. More studies will be necessary to confirm the validity of the 1-month survival predictions of this mode. Other patient populations will need to be studied to confirm its usefulness in other non-Western and non-Japanese populations. LEVEL OF EVIDENCE: Level II, prognostic study.

Pulmonary metastasis from giant cell tumor of bone: clinical outcome prior to the introduction of molecular target therapy.

OBJECTIVE: We analyzed the risk factors for pulmonary metastasis from giant cell tumor of bone and aimed to discuss their therapeutic strategy and appropriate follow-up period. METHODS: We analyzed 141 patients of giant cell tumor of bone. The variables analyzed included age, gender, primary site, Campanacci grading, surgical treatment on the primary lesion, radiotherapy and local recurrence. RESULTS: Pulmonary metastasis occurred in 12 patients. The risk factors were young age, Campanacci Grade III and local recurrence. Median time from initial surgery to metastasis was 1.3 years (0-3.1 years). Among them, eight patients experienced local recurrence of the primary tumor, and the median time from initial surgery to local recurrence was 0.8 years (0.3-2.9 years). Among seven patients who underwent wide resection, three patients showed local recurrence of the soft tissue. Nine patients underwent metastasectomy for pulmonary metastases. Of three patients who did not undergo metastasectomy, one patient died of uncontrollable metastases, and two patients showed no changes in their metastatic lesions. CONCLUSIONS: Although we found a correlation between local recurrence and pulmonary metastasis, we were still unable to prevent local or metastatic recurrence by wide resection. Local recurrence and metastasis have been found within ~3 years after initial surgery, and routine image examinations of the primary site and chest after initial surgical treatment should be considered for at least 3 years postoperatively.

Impending Atypical Femoral Fracture in Patients With Medullary Thyroid Cancer With Skeletal Metastasis Treated With Long-term Bisphosphonate and Denosumab.

Atypical femoral fractures (AFFs) occur in osteoporosis patients receiving long-term bisphosphonate. Atypical femoral fractures also occur in cancer patients receiving long-term bisphosphonate or denosumab, but the prevalence is low. We describe a 53-year-old woman with a history of medullary thyroid cancer and skull metastasis who was prescribed bisphosphonate for 6 years and denosumab for 1.5 years, consecutively. Bone scintigraphy performed because of spontaneous groin pain showed uptake in the lateral aspect of the left femur, which was confirmed as impending AFF. In oncological patients receiving long-term bisphosphonate or denosumab, AFF should be included as a differential diagnosis with focal femoral findings.

Risk factors for pneumothorax in advanced and/or metastatic soft tissue sarcoma patients during pazopanib treatment: a single-institute analysis.

BACKGROUND: After the approval of pazopanib for the treatment of soft tissue sarcoma (STS), pneumothorax was reported as an unexpected adverse event during pazopanib treatment. The incidence and risk factors of pneumothorax during pazopanib treatment for STSs have not been established yet. METHODS: We retrospectively reviewed the cases of all of the STS patients treated with pazopanib between November 2012 and December 2014 at our institute and evaluated the prevalence, incidence, treatment details and risk factors for pneumothorax in the STS patients during pazopanib treatment. RESULTS: A total of 58 patients were enrolled; 45 of them had lung and/or pleural lesions at the start of pazopanib treatment. During the median follow-up time of 219 days (range 23-659), 13 pneumothorax events occurred in six patients; the prevalence and incidence of pneumothorax were 10.3 % and 0.56 per treatment-year, respectively. The median onset of pneumothorax was day 115 (range 6-311). No patients died of pneumothorax, but pazopanib was interrupted in 10 events and chest drainage was performed in eight events. Pazopanib continuation or restart after the recovery from pneumothorax was conducted after 9 of the 13 events. The median progression-free survival of patients with and without pneumothorax events were 144 and 128 days (p = 0.89) and the median overall survival periods were 293 and 285 days (p = 0.69), respectively. By logistic regression analyses, the maximum diameter of the lung metastases ≥ 30 mm (OR 13.3, 95 % CI 1.1-155.4, p = 0.039) and a history of pneumothorax before the pazopanib induction (OR 16.6, 95 % CI 1.1-256.1, p = 0.045) were significantly predictive of pneumothorax. CONCLUSIONS: In our retrospective analysis, pneumothorax was observed in 10.3 % of 58 STS patients during pazopanib treatment. The diameter of the lung metastases and a history of pneumothorax could be useful for evaluating the risk of pneumothorax in pazopanib treatment.