Search

In this issue, Xiang and colleagues present data from the National Cancer Database comparing the number of second malignancies observed in adult and pediatric patients with 9 major cancer subtypes who received different radiation modalities. These are important findings because understanding the risk of late, radiation‐associated malignancies with different radiation modalities may help physicians reduce the risk of this devastating late treatment effect. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study.Objective: We aim to evaluate the frequency and clinical significance of additional lesions in the axial spine in subjects with chordoma and to assess the need for screening.Summary Of Background Data: Chordomas are rare tumors that may be multicentric or metastasize and affect several bones in the axial spine. The incidence of multiple lesions in the axial spine is unknown. Understanding the incidence rate of multiple lesions in the spine in subjects with chordomas will help guide utilization of total spine screening imaging.Methods: We performed a retrospective review of medical records of 42 subjects with histologically confirmed chordomas who had complete imaging of the axial spine. Lesions with imaging characteristics suggestive of chordomas/notochordal remnants were identified. Data on age at diagnosis, sex, size (in maximal dimension), type of chordoma (conventional, chondroid, or dedifferentiated), and whether pulmonary metastases were present were recorded. Binomial two-sample tests of proportions were used to compare proportions. Logistic regression was used to assess predictors of additional lesions.Results: Forty-two subjects (57.1% male) were identified. The proportion of subjects with additional lesions in the axial spine was 16.7% (7/42). Age, sex, size, and subtype of chordoma were not significant predictors of having additional lesions (P > 0.05 for each variable). However, having pulmonary metastases was a significant predictor of having additional lesions (P < 0.05).Conclusion: Approximately 17% of subjects with chordomas had additional lesions in the axial spine. It is unclear whether these represent metastases, synchronous primary chordomas or notochordal remnant tissue. Screening imaging of the axial spine may reveal additional lesions in particular in subjects with pulmonary metastases.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

This review on proton beam radiotherapy (PBT) focusses on an historical overview, cost-effectiveness, techniques, acute and late toxicities and clinical results of PBT for sarcoma patients. PBT has gained its place among the armamentarium of modern radiotherapy techniques. For selected patients, it can be cost-effective. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To present recommendations for the use of brachytherapy (BT) in patients with soft tissue sarcoma (STS). Methods: A group of practitioners with expertise and experience in sarcoma BT formulated recommendations for BT in STS based on clinical experience and literature review. Results: The indications for adjuvant BT are discussed. There is no consensus on the use of BT alone or in combination with external beam radiation therapy (EBRT), but factors that influence the selection of this modality include tumor grade and size, prior surgeries, and tumor recurrence. Low-dose-rate, high-dose-rate, and pulsed-dose-rate radiation are all acceptable BT modalities to use for STS. Recommendations are made for patient selection, techniques, dose rates, and dosages. Outcome data and toxicity data are reviewed. Conclusions: BT is a useful component of the treatment of STS. The advantages of BT are the targeted dose distribution, low integral dose, and short treatment times. Ultimately the clinician should select the modality or combination of modalities that are most familiar to the treatment team and suitable to the patient. [Copyright &y& Elsevier]

This critical review will focus on published data on the indications for radiotherapy in patients with extremity soft tissue sarcomas and its role in local control, survival, and treatment complications. The differences between pre- and postoperative radiotherapy will be discussed and consensus recommendations on target volume delineation proposed. [Copyright &y& Elsevier]

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing’s sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing’s sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging. [ABSTRACT FROM AUTHOR]

Purpose: Common practice in proton radiotherapy is to deliver a subset of all fields in the treatment plan on any given treatment day. We investigate using biological modeling if the resulting variation in daily dose to normal tissues has a relevant detrimental biological effect. Methods and Materials: For four patient groups, the cumulative normalized total dose (NTD) was determined for normal tissues (OARs) of each patient using the clinically delivered fractionation schedule (FSclin), and for hypothetical fractionation schedules delivering all fields every day (FSall) or only a single field each day (FSsingle). Cumulative three-dimensional NTD distributions were summarized using the generalized equivalent uniform dose (gEUD) model. Results: For the skull base/cervical spine chordoma group, the largest effect is a 4-Gy increase in gEUD of the chiasm when treating only a subset of fields on any day. For lung cancer and pancreatic cancer patients, the variation in the gEUD of normal tissues is <0.2 Gy. For the prostate group, FSclin increases the gEUD of the femoral heads by 9 Gy compared with FSall. Use of FSsingle resulted in the highest NTD to normal tissues for any patient. FSall resulted in an integral NTD to the patient that is on average 5% lower than FSclin and 10% lower than FSsingle. Conclusion: The effects of field set of the day treatment delivery depend on the tumor site and number of fields treated each day. Modeling these effects may be important for accurate risk assessment. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of ≥66 Gy are recommended. A Phase II clinical trial evaluated high-dose photon/proton XRT for spine sarcomas. Methods and Materials: Eligible patients had nonmetastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or postoperative photon/proton XRT with or without radical resection; patients with osteosarcoma and Ewing''s sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (Gy RBE) to subclinical disease, 70.2 Gy RBE to microscopic disease in the tumor bed, and 77.4 Gy RBE to gross disease at 1.8 Gy RBE qd. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 Gy RBE to surface/center. Intraoperative boost doses of 7.5 to 10 Gy could be given by dural plaque. Results: A total of 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). With 48 month median follow-up, 5-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence (p < 0.001). Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared after 77.12 to 77.4 Gy RBE. Conclusions: Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 Gy RBE are at risk for late toxicity. [Copyright &y& Elsevier]

Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log–rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p < 0.01), radiation dose >64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving >64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if ≤64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (>50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p < 0.01 and dose (>64 vs. ≤64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. Conclusion: Local control is achieved in most PM STS patients undergoing RT. Doses >64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure. [Copyright &y& Elsevier]

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received ≥73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by ≥73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option. [Copyright &y& Elsevier]

The article focuses on the increase in the popularity of proton beam radiation therapy among cancer patients in the U.S. The therapeutic is capable of providing superior dose distributions to patients as compared to photon therapy. Three medical centers in the U.S. that offer proton radiation are: the Northeast Proton Facility at Massachusetts General Hospital, Loma Linda University in California and Indiana University.

Purpose: Definitive radiotherapy is uncommonly used in the management of soft-tissue sarcoma (STS). The purpose of the study was to evaluate the results of radiotherapy for unresected STSs treated in a single institution. Methods and Materials: Between 1970 and 2001, 112 patients with STSs underwent radiotherapy for gross disease. Locations of the tumor were 43% in the extremities, 26% retroperitoneal, 24% in the head and neck, and 7% in the truncal wall. Histologic grades were 11% G1 and 89% G2 to G3. Median size of tumor at radiotherapy was 8 cm (range, 1–30 cm). Median radiation dose was 64 Gy (range, 25–87.5 Gy). Twenty percent of patients received chemotherapy. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated in univariate (log-rank) and then multivariate (Cox model) analysis to determine prognostic factors for STS. Results: Median follow-up for patients is 139 months (range, 30–365 months). The 5-year actuarial LC, DFS, and OS were 45%, 24%, and 35%, respectively. Tumor size at radiotherapy and radiation dose influenced LC, DFS, and OS in univariate analysis. LC at 5 years was 51%, 45%, and 9% for tumors less than 5 cm, 5 to10 cm, and greater than 10 cm, respectively. Patients who received doses of less than 63 Gy had 5-year LC, DFS, and OS rates of 22%, 10%, and 14%, respectively, compared with 5-year LC, DFS, and OS rates of 60%, 36%, and 52%, respectively, for patients who received doses of 63 Gy or more. AJCC stage was related to the OS and DFS without statistically significant influence on LC. Use of chemotherapy, histologic grade, age, and location did not influence results. In multivariate analysis, LC was related to total dose (p = 0.02), T size at radiotherapy (p = 0.003), and AJCC stage (p = 0.04); DFS was related to total dose (p = 0.007), T size at radiotherapy (p = 0.01), and AJCC stage (p < 0.0001); and OS was related to AJCC stage (p = 0.0001) and total dose (p = 0.002), but not to T size, at radiotherapy. Major radiotherapy complications were noted in 14% of patients; 27% of patients who received doses of 68 Gy or more had these complications compared with 8% of patients treated with doses of less than 68 Gy. Conclusions Definitive radiotherapy for STS should be considered in clinical situations where no acceptable surgical option is available. Higher radiation doses yield superior tumor control and survival. A rise in complications occurs in patients who receive doses of 68 Gy or more, which provides a therapeutic window for benefit in these patients. [Copyright &y& Elsevier]

Purpose: Local control of osteosarcoma in patients for whom a resection with satisfactory margins is not achieved can be difficult. This study evaluated the efficacy of radiotherapy (RT) in this setting.Methods and materials: We identified 41 patients in our sarcoma database with osteosarcomas that either were not resected or were excised with close or positive margins and who underwent RT with external beam photons and/or protons at our institution between 1980 and 2002. Patient charts were reviewed to assess local control, progression-free survival, metastasis-free survival, and overall survival.Results: The anatomic sites treated were head/face/skull in 17, extremity in 8, spine in 8, pelvis in 7, and trunk in 1. Of the 41 patients, 27 (65.85%) had undergone gross total tumor resection, 9 (21.95%) subtotal resection, and 5 (12.2%) biopsy only. The radiation dose ranged from 10 to 80 Gy (median 66). Twenty-three patients (56.1%) received a portion of their RT with protons. Chemotherapy was given to 35 patients (85.4%). Of the 41 patients, 27 (65.85%) were treated for localized disease at primary presentation, 10 (24.4%) for local recurrence, and 4 (9.8%) for metastatic disease. The overall local control rate at 5 years was 68% ± 8.3%. The local control rate according to the extent of resection was 78.4% ± 8.6% for gross total resection 77.8% ± 13.9% for subtotal resection, and 40% ± 21.9% for biopsy only (p < 0.01). The overall survival rate according to the extent of resection was 74.45% ± 9.1% for gross total resection, 74.1% ± 16.1% for subtotal resection, and 25% ± 21.65% for biopsy only (p < 0.001). Patients with either gross or subtotal resection had a greater rate of local control, survival, and disease-free survival compared with those who underwent biopsy only at 5 years (77.7% ± 7.5% vs. 40% ± 21% [p <0.001], 73.9% ± 8.1% vs. 25% ± 21.6% [p <0.001], and 51.9% ± 9.1% vs. 25% ± 21.6% [p <0.01], respectively). Overall survival was better in patients treated at primary presentation (78.8% ± 8.6% compared with 54% ± 17.3% for recurrence) p <0.05). No definitive dose–response relationship for local control of tumor was seen, although the local control rate was 71% ± 9% for 32 patients receiving doses ≥55 Gy vs. 53.6% ± 20.1% for 9 patients receiving <55 Gy (p = 0.11). Of 15 patients with tumors >5.3 cm, 9 received doses ≥55 Gy and the local control rate was 80% ± 17.9%, and 6 received doses <55 Gy with a local control rate of only 50% ± 25% at 5 years (p = 0.16). Among patients who underwent gross total resection, the local control rate was 77.5% ± 9.95% in 22 patients with negative margins vs 66.7% ± 27.2% in 3 patients with positive margins (p = 0.54). Two patients had unknown margin status.Conclusion: RT can help provide local control of osteosarcoma for patients in whom surgical resection with widely, negative margins is not possible. It appears to be more effective in situations in which microscopic or minimal residual disease is being treated. [Copyright &y& Elsevier]

: PurposeAfter vertebral or paravertebral tumor resection, tumor cells may remain on the dura. Because a tumoricidal dose is difficult to achieve using external beam radiotherapy without exceeding the spinal cord tolerance, we developed intraoperative applicators to deliver additional dose to the dura.: Methods and materialsEight patients with vertebral or paravertebral tumor underwent conformal external beam radiotherapy, tumor resection, and intraoperative radiotherapy to the dura involved by tumor. At surgery, vertebra, soft tissue, and epidural tumor were resected. A radioactive applicator plaque was placed on the dura to deliver 7.5–15 Gy, and then removed. Vertebral reconstruction and stabilization was completed. Chemotherapy was administered for large, high-grade sarcomas.: ResultsWe progressed through three plaque designs, initially 192Ir, subsequently liquid 90Y, and finally 90Y foil in a semicylindrical polycarbonate plaque, in the treatment of 8 patients. The low-energy 90Y β-emissions provided a more attractive depth dose profile than that achievable with iridium and gave negligible staff radiation exposure. The 90Y depth dose measured 29% at 2 mm and 9% at 4 mm from the surface of the foil plaque, with acceptable surface dose homogeneity. The average surface dose rate ranged from 18.7 to 47.6 cGy/min for the iridium plaques and 45.2 to 187.5 cGy/min for the 90Y plaques. The treatments have been without acute or late neurologic complications. The disease of 6 of 8 patients was locally controlled at median potential follow-up of 24 months.: ConclusionsThe 90Y foil applicator is technically elegant, easy to use, and superior to the earlier models. It has been incorporated into a protocol for spinal tumor treatment. [Copyright &y& Elsevier]

: PurposeTreatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population.: Methods and materialsAdult patients with high-grade extremity soft-tissue sarcomas ≥8 cm were treated with three cycles of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively.: ResultsAll 48 patients (M0) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% (p = 0.1155), 75% and 44% (p = 0.0016), 70% and 42% (p = 0.0002), and 87% and 58% (p = 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia.: ConclusionAfter aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial. [Copyright &y& Elsevier]

Pseudoprogression, defined as the radiographic false appearance of disease progression, is not frequently observed in patients with malignant peripheral nerve sheath tumor (MPNST). We report on a case of a patient with neurofibromatosis type 1 (NF1) MPNST pseudoprogression that presented as suspected local recurrence 9.5 years after last treatment. The patient underwent surgical resection following growth of a mass on sequential MRI imaging; surgical pathology, however, showed skeletal muscle with atrophy, fibroadipose tissue, and fat necrosis, without any evidence of tumor. As MPNST survival rates increase, physicians should consider pseudoprogression as a potential presentation after prior treatment. [ABSTRACT FROM AUTHOR]

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8–167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1–110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003–0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001–0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

The manual segmentation of organ structures in radiation oncology treatment planning is a time-consuming and highly skilled task, particularly when treating rare tumors like sacral chordomas. This study evaluates the performance of automated deep learning (DL) models in accurately segmenting the gross tumor volume (GTV) and surrounding muscle structures of sacral chordomas. An expert radiation oncologist contoured 5 muscle structures (gluteus maximus, gluteus medius, gluteus minimus, paraspinal, piriformis) and sacral chordoma GTV on computed tomography images from 48 patients. We trained 6 DL auto-segmentation models based on 3-dimensional U-Net and residual 3-dimensional U-Net architectures. We then implemented an average and an optimally weighted average ensemble to improve prediction performance. We evaluated algorithms with the average and standard deviation of the volumetric Dice similarity coefficient, surface Dice similarity coefficient with 2- and 3-mm thresholds, and average symmetric surface distance. One independent expert radiation oncologist assessed the clinical viability of the DL contours and determined the necessary amount of editing before they could be used in clinical practice. Quantitatively, the ensembles performed the best across all structures. The optimal ensemble (volumetric Dice similarity coefficient, average symmetric surface distance) was (85.5 ± 6.4, 2.6 ± 0.8; GTV), (94.4 ± 1.5, 1.0 ± 0.4; gluteus maximus), (92.6 ± 0.9, 0.9 ± 0.1; gluteus medius), (85.0 ± 2.7, 1.1 ± 0.3; gluteus minimus), (92.1 ± 1.5, 0.8 ± 0.2; paraspinal), and (78.3 ± 5.7, 1.5 ± 0.6; piriformis). The qualitative evaluation suggested that the best model could reduce the total muscle and tumor delineation time to a 19-minute average. Our methodology produces expert-level muscle and sacral chordoma tumor segmentation using DL and ensemble modeling. It can substantially augment the streamlining and accuracy of treatment planning and represents a critical step toward automated delineation of the clinical target volume in sarcoma and other disease sites. [ABSTRACT FROM AUTHOR]

Introduction. Myxoid liposarcoma (MLS) is a subtype of liposarcoma characterized morphologically by lipomatous differentiation with a myxoid stroma. The purpose of this study was to review clinical and pathological information for patients treated for MLS at our institution to better understand neoadjuvant and adjuvant therapy. Materials and Methods. An institutional database of sarcomas was queried for patients who were treated for MLS at our institution between 1992 and 2013. Survival curves were constructed using Kaplan–Meier analysis, and univariate and multivariate statistics were performed using the Cox-proportional hazards model and using linear regression. Results. A total of 85 patients with myxoid liposarcoma were identified. The mean and median histologic response rate to treatment for patients who received preoperative radiation therapy was 77.6%. Five-year disease-free survival, distant metastasis-free survival, local recurrence-free survival, and overall survival were 78.6% (95% CI: 67.8–86.1), 84.7% (95% CI: 74.5–91.0), 95.6% (95% CI: 86.9–98.6), and 87.5% (95% CI: 77.2–93.3) respectively. On univariate analysis, there was a trend towards higher necrosis or treatment response rates in patients who received concurrent chemotherapy, 84.7% (95% CI: 75.9–93.4) and 69.5% (95% CI: 55.1–83.8), p=0.061. Tumor size was associated with inferior disease-free and overall survival. Hazard ratio for disease-free survival is 1.08 (per cm) (95% CI: 1.01–1.16), p=0.019. Conclusions. Myxoid liposarcoma exhibits histological response to chemotherapy and radiation therapy. Tumor size appears to be greatest predictor of long-term disease control and overall survival. We were not able to show that chemotherapy provides a clinical benefit with regard to local control, disease-free survival, or overall survival. However, it is important to note that the selected usage of chemotherapy in the highest risk patients confounds this analysis. Further investigation is needed to help better determine the optimal use of chemotherapy in this group of patients. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 45-year-old woman diagnosed with fibrous histiocytoma and Pancoast's Syndrome. She was admitted to the hospital because of a mass at the apex of her right lung. Three and a half years before admission, she began to have paresthesias in the fourth and fifth fingers of her right hand. Nine months before admission, she noted anhidrosis on the right side of her face. On examination, the patient appeared well but was overweight. There was no lymphadenopathy. Her lungs were clear. Her heart and breasts were normal. A magnetic resonance imaging showed a mass at the apex of the right hemithorax. Cytologic evaluation revealed small numbers of benign-appearing spindle cells present as naked nuclei in fibrous stroma, however, no malignant cells were seen.

• High-dose radiation therapy should be considered for unresected chordoma patients. • High-dose radiotherapy achieved by proton-based treatment has acceptable toxicity. • Large tumor volume is associated with worse disease-free survival post-radiotherapy. Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain locations, resection may result in significant neurological dysfunction, so definitive radiation has been used as an alternative to surgery. The purpose of this study is to report the results of high-dose, proton-based definitive radiotherapy for unresected spinal and sacral chordomas. Retrospective review of 67 patients with newly diagnosed, unresected spinal chordomas treated with high-dose definitive, proton-based radiotherapy at our center from 1975 to 2019. Reasons for radiotherapy alone included medical inoperability and/or concern for neurological dysfunction based on spine level or patient choice. Tumor locations included cervical (n = 10), thoracic (n = 1), lumbar (n = 4) spine, and sacrum (n = 52). Median maximal tumor diameter was 7.4 cm (range 1.8–25 cm). Median total dose was 77.4 Gy (RBE) (range 73.8–85.9 Gy RBE). Analysis with median follow-up of 56.2 months (range, 4–171.7 months) showed overall survival of 83.5 % (95%CI: 69.4–91.5%) and 65.9% (95%CI: 47.3–79.3%), disease-free survival of 64% (95%CI: 49.3–75.4) and 44.1% (95%CI: 27.8–59.2%), local control of 81.8% (95%CI: 67.6–90.2%) and 63.6% (95%CI: 44.7–77.5%), and distant control of 77.4% (95%CI: 63.6–86.5%) and 72.5% (95%CI: 55.7–83.8%) at 5 and 8 years respectively. The most common late side effect was insufficiency fracture. These results continue to support the use of high-dose definitive radiotherapy for patients with medically inoperable or otherwise unresected mobile spine or sacrococcygeal chordomas. There is a trend towards better disease-free survival with doses > 78 Gy (RBE). [ABSTRACT FROM AUTHOR]

Background. External beam radiation therapy (RT) for retroperitoneal sarcoma often requires treatment of large target volumes close to critical normal tissues. Radiation may be limited by adjacent organs at risk (OAR). Intensity-modulated radiation therapy has been shown to improve target coverage and reduce doses to OAR. Objectives. To compare target coverage and dose to OAR with 3D conformal proton therapy (3D CPT), intensity-modulated proton therapy (IMPT), and intensity-modulated photon therapy (IMXT). Methods. We performed a comparative study of treatment plans with 3D CPT, IMPT, and IMXT for ten patients with retroperitoneal sarcomas. RT was delivered to 50.4 Gy to the clinical target volume (CTV), the structures considered at risk for microscopic disease. Results. CTVs ranged from 74 to 357 cc (mean 188 cc). Dose conformity was improved with IMPT, while 3D CPT provided better dose homogeneity. Mean dose to the liver, small bowel, and stomach was reduced with IMPT compared with 3D CPT or IMXT. Conclusions. IMPT, 3D CPT, and IMXT provide excellent target coverage for retroperitoneal sarcomas. OAR dose is lower with IMPT and 3D CPT, and IMPT achieves the closest conformity. These techniques offer the opportunity for further dose escalation to areas with positive margins. [ABSTRACT FROM AUTHOR]

: PurposeA comparative treatment planning study has been undertaken between intensity modulated (IM) photon therapy and IM proton therapy (IMPT) in paraspinal sarcomas, so as to assess the potential benefits and limitations of these treatment modalities. In the case of IM proton therapy, plans were compared also for two different sizes of the pencil beam. Finally, a 10% and 20% dose escalation with IM protons was planned, and the consequential organ at risk (OAR) irradiation was evaluated.: Methods and materialsPlans for 5 patients were computed for IM photons (7 coplanar fields) and protons (3 coplanar beams), using the KonRad inverse treatment planning system (developed at the German Cancer Research Center). IMPT planning was performed assuming 2 different sizes of the pencil beam: IMPT with a beam of full width at half-maximum of 20 mm, and IMPT with a “mini-beam” (IMPTM, full width at half-maximum = 12 mm). Prescribed dose was 77.4 Gy or cobalt Gray equivalent (CGE) for protons to the gross tumor volume (GTV). Surface and center spinal cord dose constraint for all techniques was 64 and 53 Gy/CGE, respectively. Tumor and OAR dose–volume histograms were calculated. Results were analyzed using dose–volume histogram parameters, inhomogeneity coefficient, and conformity index.: ResultsGross tumor volume coverage was optimal and equally homogeneous with both IM photon and IM proton plans. Compared to the IM photon plans, the use of IM proton beam therapy leads to a substantial reduction of the OAR total integral dose in the low-level to mid-dose level. Median heart, lung, kidney, stomach, and liver mean dose and dose at the 50% volume level were consistently reduced by a factor of 1.3 to 25. Tumor dose homogeneity in IMPTM plans was always better than with IMPT planning (median inhomogeneity coefficient, 0.19 vs. 0.25). IMPT dose escalation (to 92.9 CGE to the GTV) was possible in all patients without exceeding the normal-tissue dose limits.: ConclusionsThese results suggest that the use of IM photon therapy, when compared to IM protons, can result in similar levels of tumor conformation. IM proton therapy, however, reduces the OAR integral dose substantially, compared to IM photon radiation therapy. As a result, tumor dose escalation was always possible with IM proton planning, within the maximal OAR dose constraints. In IM proton planning, reducing the size of the proton pencil beam (using the “mini-beam”) improved the dose homogeneity, but it did not have a significant effect on the dose conformity. [Copyright &y& Elsevier]

Background. Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. Methods. In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors. Results. Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis. Conclusions. The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients. [ABSTRACT FROM AUTHOR]

Background: We developed a machine learning algorithm to predict the survival of patients with chondrosarcoma. The algorithm demonstrated excellent discrimination and calibration on internal validation in a derivation cohort based on data from the Surveillance, Epidemiology, and End Results (SEER) registry. However, the algorithm has not been validated in an independent external dataset.Questions/purposes: Does the Skeletal Oncology Research Group (SORG) algorithm accurately predict 5-year survival in an independent patient population surgically treated for chondrosarcoma?Methods: The SORG algorithm was developed using the SEER registry, which contains demographic data, tumor characteristics, treatment, and outcome values; and includes approximately 30% of the cancer patients in the United States. The SEER registry was ideal for creating the derivation cohort, and consequently the SORG algorithm, because of the high number of eligible patients and the availability of most (explanatory) variables of interest. Between 1992 to 2013, 326 patients were treated surgically for extracranial chondrosarcoma of the bone at two tertiary care referral centers. Of those, 179 were accounted for at a minimum of 5 years after diagnosis in a clinical note at one of the two institutions, unless they died earlier, and were included in the validation cohort. In all, 147 (45%) did not meet the minimum 5 years of followup at the institution and were not included in the validation of the SORG algorithm. The outcome (survival at 5 years) was checked for all 326 patients in the Social Security death index and were included in the supplemental validation cohort, to also ascertain validity for patients with less than 5 years of institutional followup. Variables used in the SORG algorithm to predict 5-year survival including sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location were collected manually from medical records. The tumor characteristics were collected from the postoperative musculoskeletal pathology report. Predicted probabilities of 5-year survival were calculated for each patient in the validation cohort using the SORG algorithm, followed by an assessment of performance using the same metrics as used for internal validation, namely: discrimination, calibration, and overall performance. Discrimination was calculated using the concordance statistic (or the area under the Receiver Operating Characteristic (ROC) curve) to determine how well the algorithm discriminates between the outcome, which ranges from 0.5 (no better than a coin-toss) to 1.0 (perfect discrimination). Calibration was assessed using the calibration slope and intercept from a calibration plot to measure the agreement between predicted and observed outcomes. A perfect calibration plot should show a 45° upwards line. Overall performance was determined using the Brier score, ranging from 0 (excellent prediction) to 1 (worst prediction). The Brier score was compared with the null-model Brier score, which showed the performance of a model that ignored all the covariates. A Brier score lower than the null model Brier score indicated greater performance of the algorithm. For the external validation an F1-score was added to measure the overall accuracy of the algorithm, which ranges between 0 (total failure of an algorithm) and 1 (perfect algorithm).The 5-year survival was lower in the validation cohort than it was in the derivation cohort from SEER (61.5% [110 of 179] versus 76% [1131 of 1544] ; p < 0.001). This difference was driven by higher proportion of dedifferentiated chondrosarcoma in the institutional population than in the derivation cohort (27% [49 of 179] versus 9% [131 of 1544]; p < 0.001). Patients in the validation cohort also had larger tumor sizes, higher grades, and nonextremity tumor locations than did those in the derivation cohort. These differences between the study groups emphasize that the external validation is performed not only in a different patient cohort, but also in terms of disease characteristics. Five-year survival was not different for both patient groups between subpopulations of patients with conventional chondrosarcomas and those with dedifferentiated chondrosarcomas.Results: The concordance statistic for the validation cohort was 0.87 (95% CI, 0.80-0.91). Evaluation of the algorithm's calibration in the institutional population resulted in a calibration slope of 0.97 (95% CI, 0.68-1.3) and calibration intercept of -0.58 (95% CI, -0.20 to -0.97). Finally, on overall performance, the algorithm had a Brier score of 0.152 compared with a null-model Brier score of 0.237 for a high level of overall performance. The F1-score was 0.836. For the supplementary validation in the total of 326 patients, the SORG algorithm had a validation of 0.89 (95% CI, 0.85-0.93). The calibration slope was 1.13 (95% CI, 0.87-1.39) and the calibration intercept was -0.26 (95% CI, -0.57 to 0.06). The Brier score was 0.11, with a null-model Brier score of 0.19. The F1-score was 0.901.Conclusions: On external validation, the SORG algorithm retained good discriminative ability and overall performance but overestimated 5-year survival in patients surgically treated for chondrosarcoma. This internet-based tool can help guide patient counseling and shared decision making.Level Of Evidence: Level III, prognostic study. [ABSTRACT FROM AUTHOR]

Purpose: Definitive chemoradiation with concurrent 5-fluorouracil (5-FU)/mitomycin C (MMC) is an effective treatment for localized anal cancer, but it is associated with significant acute long-term treatment-related toxicity. Pencil beam scanning proton beam (PBS-PT) radiation therapy may potentially reduce this toxicity. This is a multi-institutional pilot study evaluating the feasibility of definitive concurrent chemoradiation with PBS-PT in combination with 5-FU and MMC for carcinoma of the anal canal.Methods and Materials: Patients were enrolled on a National Cancer Institute-sponsored, prospective, multi-institutional, single-arm pilot study (NCT01858025). Key eligibility criteria included Eastern Cooperative Oncology Group 0 to 2, age ≥18 years, histologically confirmed invasive squamous cell carcinoma of the anal canal, and clinically staged T1-4, N0-3 disease. Patients were treated with PBS-PT per Radiation Therapy Oncology Group 0529 dose schema and concurrent 5-FU/MMC on day 1 and 29. The primary objective of this study was to determine feasibility of PBS-PT with concurrent 5-FU/MMC, defined as grade 3+ dermatologic toxicity less than 48% (reported grade 3+ dermatologic toxicity from Radiation Therapy Oncology Group 98-11). Secondary objectives were to determine the rates of overall grade 3+ toxicities, clinical complete response rate, and disease outcomes.Results: Between February 2014 and April 2017, we enrolled 25 patients into our study, all of whom were analyzed. Twenty-three patients (92%) completed treatment per protocol, and 2 patients died on treatment. Median time to completion of treatment was 42 days (range, 38-49). The grade 3+ radiation dermatitis rate was 24%. Median follow-up is 27 months (range, 21-50) among the 21 patients still alive. The overall rate of clinical complete response was 88%. The 2-year local failure, colostomy-free survival, progression-free survival, and overall survival are 12%, 72%, 80%, and 84%, respectively.Conclusions: In our prospective, multi-institutional pilot study of PBS-PT with concurrent 5-FU/MMC, PBS-PT was found to be feasible. A phase 2 study of proton beam radiation therapy is currently underway. [ABSTRACT FROM AUTHOR]

Purpose: Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC.Methods and Materials: This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12 months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3 months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date.Results: The median follow-up was 14 months. Of 133 patients with median age 68 years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P = .008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14 months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P = .03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3 months was associated with worse OS (adjusted hazard ratio, 3.83; P < .001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons.Conclusions: Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC. [ABSTRACT FROM AUTHOR]

• Both radiation-induced and neurofibromatosis-associated MPNSTs have poorer prognosis than sporadic MPNSTs. • Complete resection of the tumor is a significant prognostic factor for MPNST. • Surgery with adjuvant radiotherapy is related to improved local control in patients with positive surgical margins. Malignant peripheral nerve sheath tumors (MPNST) may be sporadic or associated with neurofibromatosis or prior radiation. MPNST may behave aggressively with a high rate of local recurrence and distant metastasis. In an IRB approved protocol, we reviewed the clinical characteristics, treatment, and outcomes of 280 patients treated for MPNST at Massachusetts General Hospital (MGH) between 1960 and 2016. There were 138 men and 142 women with a median age of 41 (range: 3–95) years. Tumors were classified as neurofibromatosis-associated (nfMPNST, n = 77), radiation-induced (rMPNST, n = 21), or sporadic (sMPNST, n = 182) MPNST. The median time to development of rMPNST from prior radiation was 15 years. With a median follow-up of 43.1 months, the median overall survival (OS) was 65.3 months. Older age, nfMPNST, rMPNST, increased tumor size, lymph node involvement, metastatic disease, intermediate to high grade, radiotherapy alone, and R2 resection were related to worse OS, whereas surgery with radiotherapy was associated with improved OS. Among the 251 patients without metastasis, nfMPNST, rMPNST, and increased tumor size were correlated with worse metastasis-free survival; nfMPNST, radiotherapy alone, and R1/R2 resection were associated with local recurrence, whereas surgery with adjuvant radiotherapy was related to improved local control in patients with R1/R2 resection. Both radiation-induced and neurofibromatosis-associated MPNSTs have poorer prognosis than sporadic MPNSTs. Complete resection of the tumor is a significant prognostic factor for MPNST. The addition of radiotherapy after surgery should be considered especially when the surgical margins are positive. [ABSTRACT FROM AUTHOR]

Background: Local recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors. High-quality studies comparing presentation and treatments for primary and first local recurrent sacral chordoma tumors are sparse.Purpose: To determine: whether there is a difference in how primary and tumors at first recurrence present; the overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a primary tumor; overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a first local relapse; if there any differences in overall survival, local relapse-free survival, and distant relapse-free survival rates between patients presenting with a primary tumor and those with a first local relapse.Study Design: Retrospective case series.Patient Sample: One hundred one sacral chordoma cases.Outcome Measure: Overall survival, local relapse-free survival, and distant relapse-free survival rates.Methods: Between 1978 and 2013, 131 patients with sacral chordoma were seen. Of them, 17 patients (13%) presented with a history of more than one local recurrence. One patient (1%) presented with multiple distant metastases. Ten patients (8%) had less than 36 months of follow-up and had no event (eg, death, local recurrence, or distant metastasis). A total of 102 patients met our inclusion criteria: patients with primary or first recurrent tumors, without metastatic disease, who underwent surgery and with at least 36 months of follow-up. One patient (1%) died intraoperatively; therefore, 101 patients were included in the present analysis. Cox proportional hazards regression analysis was performed for primary and local recurrent tumor separately and to compare primary and local recurrent tumors.Results: We analyzed 73 primary and 28 first time recurrent sacral chordomas. Tumor size at presentation was different for primary and recurrent tumors (primary median size: 158 cm3, interquartile range [IQR]: 46-634; recurrent median size: 39 cm3, IQR: 14-175; p=.001). Overall survival at 5 and 10years for the primary tumors was 79% and 59%, respectively. Local relapse-free survival at 5years was 86%. For primary tumors, not receiving radiation was an independent predictor for worse local relapse-free survival (hazard ratio [HR]: 0.20; 95% confidence interval [CI]: 0.0043-0.90; p=.004) and increased tumor size was an independent predictor for both worse overall survival (HR: 1.68; 95% CI: 1.38-2.42; p=.004) and worse distant relapse-free survival (HR: 2.25; 95% CI: 1.47-3.44; p<.001). For recurrent tumors, the 5- and 10-year overall survival was 65% and 40%, respectively. Local relapse-free survival at 5years was 79% for recurrent tumors. On bivariate analysis, increased tumor size was a significant predictor for worse survival (LR median: 338 mL; IQR: 218-503 mL; no LR median: 26 mL; IQR: 9-71 mL). A trend was seen toward better distant relapse survival for tumors presenting as a primary tumor (HR: 0.51; 95% CI: 0.25-1.06; p=.072).Conclusion: Using a combination of surgical resection and adjuvant radiotherapy allowed us to obtain a good overall survival, local relapse-free survival, and distant relapse-free survival in patients presenting with either a primary tumor or with a first time local recurrent tumor. [ABSTRACT FROM AUTHOR]

Purpose: Long-term survivors of Ewing sarcoma (ES) and osteosarcoma may be at risk for therapy-related acute leukemia or myelodysplastic syndrome (t-AL/MDS).Methods and Materials: We retrospectively reviewed the clinicopathologic characteristics of 1071 patients with osteosarcoma (n = 757) and ES (n = 314) who were treated between 1985 and 2014. Multivariable competing risk analysis was used to analyze predictors of t-AL/MDS, including a radiation dose (≥55.8 Gy vs <55.8 Gy) × disease site (pelvis/spine vs other) interaction term. A supplemental nested case-control study was conducted to assess the association between cumulative chemotherapy dose and t-AL/MDS.Results: The median follow-up for surviving patients was 97 months (range, 0.03-380). Twenty patients developed t-AL/MDS, all of whom received chemotherapy and 15 of whom were treated with radiation therapy. Radiation therapy to ≥55.8 Gy was associated with development of t-AL/MDS (adjusted hazard ratio, 2.89; 95% confidence interval [CI], 1.23-6.80; P = .015), and there was a significant radiation dose × disease site interaction term (adjusted hazard ratio, 6.70; 95% CI, 2.71-16.53; Pinteraction < .001). The 5-year cumulative incidence of t-AL/MDS in patients receiving ≥55.8 Gy radiation therapy to the pelvis or spine was 5.0% (95% CI, 0.9-14.9) for osteosarcoma and 10.7% for ES (95% CI, 3.3-23.2). In our nested case-control study, cumulative doses of ifosfamide and etoposide were associated with development of t-AL/MDS.Conclusions: Patients with osteosarcoma and ES receiving ≥55.8 Gy of radiation therapy to the pelvis or spine appear to be at increased risk for t-AL/MDS. Treatment with high cumulative doses of chemotherapy may further augment this risk. [ABSTRACT FROM AUTHOR]

Purpose: Chordomas are malignant tumors arising from remnant notochordal tissue. Despite improved local control with preoperative/postoperative radiation therapy (RT), progression-free survival and overall survival (OS) remain poor in patients with high-risk features. Chordoma has been identified to express and activate platelet-derived growth factor receptor signaling. We conducted a phase 1 trial to identify the maximum tolerated dose (MTD), safety, and feasibility of nilotinib with RT as either preoperative or definitive treatment for patients with high-risk chordoma.Methods and Materials: We recruited 23 patients with high-risk, nonmetastatic chordoma. High risk was defined as the presence of any of the following: local recurrence after surgery, previous intralesional resection, unplanned incomplete resection, unresectable or marginally resectable disease based on locally advanced stage, or declining surgery because of excessive morbidity. Patients were treated with nilotinib and concurrent RT to 50.4 Gy relative biological effectiveness (RBE) followed by surgery and postoperative RT to a cumulative dose up to 70.2 Gy RBE or definitively up to 77.4 Gy RBE without surgery. On completion of RT, patients were eligible to continue nilotinib until disease progression.Results: In patients receiving nilotinib 200 mg twice daily with RT, 3 dose-limiting toxicities (DLT) occurred in 5 patients. One DLT was seen among 6 patients receiving nilotinib 200 mg daily with RT. Therefore, 200 mg daily was declared the maximum tolerated dose. Eleven additional patients received nilotinib with RT at the maximum tolerated dose, and 1 additional DLT occurred. The objective best response rate was 6% (1 of 18 patients, 95% confidence interval [CI], 0.1%-27%). The median progression-free survival was 58.15 months (95% CI, 39.10-∞). The median OS was 61.5 months (43.1-∞), and the 2-year OS rate was 95%.Conclusions: Nilotinib 200 mg/d with RT is safe and tolerated in patients with high-risk chordoma. Long-term follow-up is needed to understand whether nilotinib combined with RT, with or without surgery, adds greater improvement to progression-free survival or OS than with RT with or without surgery alone in patients with high-risk chordoma. [ABSTRACT FROM AUTHOR]

Purpose: Irradiation may have significant immunomodulatory effects that impact tumor response and could potentiate immunotherapeutic approaches. The purposes of this study were to prospectively investigate circulating lymphoid cell population fractions during hypofractionated proton therapy (HPT) in blood samples of liver cancer patients and to explore their association with survival.Methods and Materials: We collected serial blood samples before treatment and at days 8 and 15 of HPT from 43 patients with liver cancer-22 with hepatocellular carcinoma (HCC) and 21 with intrahepatic cholangiocarcinoma (ICC)-enrolled in a phase 2 clinical trial. All patients received 15 fractions of proton therapy to a median dose of 58 Gy (relative biological effectiveness). We used flow cytometry to measure the changes in the fractions of total CD3+, CD4+, and CD8+ T cells; CD4+ CD25+ T cells; CD4+ CD127+ T cells; CD3+ CD8+ CD25+ activated cytotoxic T lymphocytes (CTLs); and CD3- CD56+ natural killer cells.Results: With a median follow-up period of 42 months, median overall survival (OS) in the study cohort was 30.6 months for HCC and 14.5 months for ICC patients. Longer OS was significantly correlated with greater CD4+ CD25+ T-cell (P = .003) and CD4+ CD127+ T-cell (P = .01) fractions at baseline only in ICC patients. In HCC patients, the fraction of activated CTLs mid treatment (at day 8) was significantly associated with OS (P = .007). These findings suggest a differential relevance of immunomodulation by HPT in these liver cancers.Conclusions: Antitumor immunity may depend on maintenance of a sufficiently high number of activated CTLs during HPT in HCC patients and CD4+ CD25+ T cells and CD4+ CD127+ T cells prior to treatment in ICC patients. These results could guide the design of future studies to determine the optimal treatment schedules when combining irradiation with specific immunotherapy approaches. [ABSTRACT FROM AUTHOR]

Purpose: Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of large prospective studies on radiation therapy (RT) with definitive and/or palliative intent in SFT patients, this retrospective study aimed to better define the benefit of RT in this disease.Methods and Materials: A retrospective observational study was performed across 7 sarcoma centers. Clinical information was retrieved from all patients receiving RT without surgery over the course of their locally advanced and/or metastatic disease. Differences in treatment characteristics between subgroups were tested using analysis-of-variance tests. Local control (LC) and overall survival (OS) rates were calculated as time from the start of RT until local progression and death from any cause, respectively.Results: Since 1990, a total of 40 patients were identified. RT was applied with definitive intent in 16 patients and with palliative intent in 24. The median follow-up period was 62 months. In patients treated with definitive RT (receiving approximately 60 Gy), the objective response rate was 67%. At 5 years, the LC rate was 81.3%, and the OS rate was 87.5%. In the case of palliative RT (typically 39 Gy), the objective response rate was 38%. The LC and OS rates at 5 years were 62.5% and 54.2%, respectively. In both subgroups, RT-associated toxicities were mild with predominantly grade 1 acute and late side effects.Conclusions: This retrospective study suggests a clinically meaningful benefit for RT given with either definitive or palliative intent without surgery in SFT management. Prospective registries potentially in collaboration with patient advocacy groups are warranted to further assess the role of RT in patients with this rare malignancy. [ABSTRACT FROM AUTHOR]

Purpose: To compare rates of secondary acute leukemia between sarcoma patients and the general population, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry, and to examine whether various patient, tumor, and treatment factors were associated with development of a secondary acute leukemia.Methods and Materials: Patients with a primary diagnosis of connective tissue malignancy between 1973 and 2008 in the SEER database were included. Multivariable competing risk analysis was used to determine risk factors associated with subsequent development of acute leukemia. Using observed-to-expected ratios, we compared incidence rates of secondary acute leukemia between sarcoma patients and the general population.Results: A total of 72,945 patients were identified, with median follow-up of 131 months. On multivariable competing risk analysis, factors associated with increased risk of secondary acute leukemia included receipt of radiation therapy (hazard ratio [HR] 1.67, P=.02), distant disease (HR 2.67, P=.004), male gender (HR 1.53, P=.03), year of diagnosis (HR 0.98, P=.049), and Ewing sarcoma histology (HR 9.95, P < .0001) and osteosarcoma histology (HR 5.06, P=.0001). The observed-to-expected ratio for development of a secondary acute leukemia was 3.67 (95% confidence interval [CI] 1.95-6.28), 3.41 (95% CI 2.73-4.20), and 1.6 (95% CI 1.38-8.19) for acute lymphocytic leukemia, acute myeloid leukemia, and acute monocytic leukemia, respectively. The 10-year cumulative incidence of secondary acute leukemia for patients who did and did receive radiation therapy was 0.3% versus 0.1% (P=.02).Conclusions: Patients treated for sarcoma, in particular those with Ewing sarcoma and osteosarcoma histology, seem to have a higher incidence of secondary acute leukemia as compared with the general population. Treatment factors including radiation therapy and chemotherapy seem to play a role in this increased risk, although the absolute incidence nevertheless remains very small. [ABSTRACT FROM AUTHOR]

Abstract: Background: Nonretroperitoneal abdominal soft tissue sarcoma (NRA‐STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. Materials: The analysis included patients with resected high‐grade NRA‐STS. Chi‐square analysis was used to evaluate distribution of patient and tumor‐related factors within treatment groups. The Kaplan–Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients’ outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. Results: At median follow‐up of 49 months, 5‐year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58–0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Conclusion: Adjuvant radiotherapy was associated with improved survival in high‐grade NRA‐STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: This study is to present a large cohort of extraskeletal osteosarcoma (ESOS) and evaluate prognostic factors and treatment options. Methods: Medical records were reviewed retrospectively for 41 patients with extraskeletal osteosarcoma that was diagnosed by pathology, and treated at our institution between 1960 and 2016. Kaplan-Meier analysis and Cox proportional hazards regression were used to identify variables that affect survival outcomes. Results: 41 patients were identified from 952 osteosarcomas. 32 patients had non-metastatic disease. Prognostic factors were identified by univariate analysis and multi-variate analysis. Surgery (p<0.001), and surgery type (p<0.001) both were shown to significantly affect overall survival (OS). Chemotherapy and radiation therapy (RT) did not show any significant effect on OS, local recurrence, or progression free survival as a whole. However for patients who had incomplete resection with residual tumor RT improved OS (p=0.03). The survival curve for ESOS follows more closely that of nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). Conclusions: ESOS is a very rare tumor. Attempt to achieve wide resection is the treatment of choice. However for patients who are not able to achieve complete resection, RT may improve OS. The behavior of ESOS more closely follows that of NRSTS than osteosarcoma of the bone. [ABSTRACT FROM AUTHOR]

Purpose Intergroup 9514 reported promising outcomes with neoadjuvant chemoradiotherapy for large extremity/trunk soft tissue sarcoma (ESTS). One decade later, optimum integration of chemotherapy and radiotherapy into the perioperative management of ESTS remains to be defined. Methods The National Cancer Data Base was used to identify 3422 patients who underwent resection for large (>8 cm) high-grade STS between 2004 and 2013. Chi-square analysis was used to evaluate distribution of patient and tumor related factors within treatment groups while multivariate analyses were used to determine the impact of these factors on patient outcome. The Kaplan Meier method and Cox proportional hazards model were utilized to evaluate overall survival according to treatment regimen, with a secondary analysis based on propensity score matching to control for prescription bias and potential confounders imbalance. Results Hazard ratio for death was reduced by 35% with radiotherapy and 24% with chemotherapy, compared to surgery alone. Combination therapy incorporating both modalities improved 5-yr survival (62.1%) compared to either treatment alone (51.4%). The sequencing of chemotherapy and radiotherapy or whether they were delivered as adjuvant vs. as neoadjuvant therapy did not affect their efficacy. Age > 50 years, tumor size > 11 cm, and tumor location on the trunk/pelvis were poor prognostic factors. Conclusion Our analysis suggests that adjunctive modalities are both critical in the treatment of large high-grade ESTS, improving survival when used individually and demonstrating synergy in combination, regardless of sequencing relative to each other or relative to surgery; thus providing a framework for future randomized trials. [ABSTRACT FROM AUTHOR]

Purpose: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma.Methods and Materials: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system.Results: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher.Conclusions: Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy.Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis.Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume.Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas. Assessment of tumor response to radiation therapy by volumetric analysis is superior to modified RECIST in chordoma patients. Evaluating the soft tissue target volume is an excellent indicator of tumor response. [ABSTRACT FROM AUTHOR]

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy.Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0.Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity.Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton therapy in the treatment of sinonasal malignancy. [ABSTRACT FROM AUTHOR]

Introduction: This critical review aims to summarize published data on limb sparing surgery for extremity soft tissue sarcoma in combination with pre-operative radiotherapy (RT). Methods: This review is based on peer-reviewed publications using a PubMed search on the MeSH headings “soft tissue sarcoma” AND “preoperative radiotherapy”. Titles and abstracts screened for data including “fraction size AND/OR total dose AND/OR overall treatment time”, “chemotherapy”, “targeted agents AND/OR tyrosine kinase inhibitors”, are collated. Reference lists from some articles have been studied to obtain other pertinent articles. Additional abstracts presented at international sarcoma meetings have been included as well as information on relevant clinical trials available at the ClinicalTrials.gov website. Results: Data are presented for the conventional regimen of 50–50.4 Gy in 25–28 fractions in 5–6 of weeks preoperative external beam RT with respect to the regimen’s local control probability compared to surgery alone, as well as acute and late toxicities. The rationale and outcome data for hypofractionated and/or reduced dose regimens are discussed. Finally, combination schedules with conventional chemotherapy and/or targeted agents are summarized. Conclusion: Outside the setting of well-designed prospective clinical trials, the conventional 50 Gy in 5–6 week schedule should be considered as standard. However, current and future studies addressing alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may reveal regimens of equal or increased efficacy with reduced late morbidities. [ABSTRACT FROM AUTHOR]

Purpose To evaluate and understand the tolerance of the thoracolumbar spinal cord using equivalent uniform dose (EUD) and dose volume histogram (DVH) analysis after combined high dose photon–proton radiotherapy. Materials and methods A total of 68 patients were identified as having high dose radiotherapy, ⩾5900 cGy (RBE) in the region of the thoracolumbar spinal cord, defined as extending inferiorly to L2. Pathological diagnosis for patients in this review included chordoma (50 patients, 53.1%), chondrosarcoma (28 patients, 29.8%), osteosarcoma (3 patients, 3.2%), other sarcoma (11 patients, 11.7%), and other (2 patients, 2.1%). Patient data were reviewed retrospectively, detailed dose volume histogram data (DVH) were available for 23 patients. Composite plans and DVH were constructed for both pre-operative and post-operative radiation therapy courses in MIM-Vista software, as available. Dose constraints to the center and surface of the cord were 5400 cGy (RBE), and 6300 cGy (RBE) respectively, and patients receiving concurrent chemotherapy received an eight percent dose reduction. Spinal cord toxicity was recorded using the RTOG/EORTC late effects scoring system. Results Clinical and dosimetric data for each patient were analyzed. Median prescription dose was 7020 cGy (RBE), range (5940–7820 cGy (RBE)). Median follow-up was 12.9 months. Five-year overall survival for all patients in this group was 88.7%, 95%CI (74.7–95.2). One patient suffered from transient paralysis following stem cell transplant for treatment of myelodysplastic syndrome. Other reasons for spinal cord injury following treatment included: local disease progression, noted in 7 patients (10.3%), and direct result of surgery, noted in 8 patients (11.8%). Freedom from neurological injury (RTOG Grade 2 or higher) at 5 years was 92.9%(95%CI: 74.6–98.2), at 6 years was 80.9%(95%CI: 55.3–92.7), and at 8 years 80.9%(95%CI: 55.3–92.7). Conclusion Our clinical and dosimetric data suggest that the noted dose constraints are safe and acceptable with regard to spinal cord complications. Pre-existing disease characteristics, surgical complications, as well as tumor progression, appear to be more important factors when it comes to spinal cord toxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Surgery with high-dose radiation and high-dose radiation alone for sacral chordomas have shown promising local control rates. However, we have noted frequent sacral insufficiency fractures and perceived this rate to be higher than previously reported.Questions/purposes: We wished (1) to characterize the incidence of sacral insufficiency fractures in patients with chordomas of the sacrum who received high-dose radiation, and (2) to determine whether patients treated with surgery plus high-dose radiation or high-dose radiation alone are more likely to experience a sacral fracture, and to compare time to fracture in these groups.Methods: Sixty-two patients who received high-dose radiation for sacral chordomas with (n = 44) or without surgical resection (n = 18) between 1992 and 2013 were included in this retrospective study. At our institution, sacral chordomas generally are treated by preoperative radiotherapy, followed by en bloc resection, and postoperative radiotherapy. Radiation alone, with an intent to cure, is offered to patients who otherwise are not good surgical candidates or patients who elect radiotherapy based on tumor location and the anticipated morbidity after surgery (such as sexual, bowel, or bladder dysfunction). MRI and CT scans were evaluated for evidence of sacral insufficiency fractures. Complete followup was available at a minimum of 2 years (or until fracture or death) for all 18 patients who underwent radiation alone, whereas 14% (six of 44 patients) in the surgery plus radiation group (9% [three of 33] after high sacrectomy and 27% [three of 11] after low sacrectomy) were lost to followup before 2 years.Results: Sacral insufficiency fractures occurred in 29 of the 62 patients (47%). A total of 25 of 33 patients (76%) with high sacrectomy had fractures develop compared with zero of 11 (0%) after low sacrectomy, and four of the 18 patients (22%) who had high-dose radiation alone (p < 0.001). The fracture rate was greater in the high sacrectomy group than in the low sacrectomy group (p < 0.001) and the radiation only group (p < 0.001). There was no difference with the numbers evaluated in fracture probability between patients in the low-sacrectomy group and those treated with radiation alone (p = 0.112). The fracture-free survival probability was 0.99 for the low sacrectomy group at all times as there were no insufficiency fractures in this group; the 1-year fracture-free survival probability was 0.53 (95% CI, 0.35-0.69) after high sacrectomy, 0.83 (95% CI, 0.57-0.94) after radiation alone; the 2-year fracture-free survival probability was 0.36 (95% CI, 0.19-0.52) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone; and the 5-year fracture-free survival probability was 0.14 (95% CI, 0.04-0.30) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone.Conclusions: Acknowledging the limitations of potential differences in baseline and followup among treatment groups in our study, we found that almost ½ of our patients experienced an insufficiency fracture. We found that the fracture rate was greater in the surgery group compared with the radiation alone group and that high sacrectomy accounted for all fractures in the surgery group. These findings can be used to inform patients and also support the need for further research to elucidate the influence of high-dose radiation on bone quality.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Chordoma is a rare, slow-growing malignant tumor arising from notochordal remnants. A retrospective review of patient records at two major referral centers was undertaken to assess the incidence, location, and prognostic factors of metastatic disease from chordoma. 219 patients with chordoma (1962–2009) were identified. 39 patients (17.8%) developed metastatic disease, most frequently to lung (>50%). Median survival from the time of initial diagnosis was 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not (P=0.05). Metastatic disease was most common in the youngest patients (P=0.07), and it was 2.5 times more frequent among patients with local recurrence (26.3%) than in those without (10.8%) (P=0.003). Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary and the site of metastasis. Metastasis to distal bone was the most rapid to develop and had the worst prognosis. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed. [ABSTRACT FROM AUTHOR]