Bone cancer.

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.

Neoadjuvant Chemoradiation Compared With Neoadjuvant Radiation Alone in the Management of High-Grade Soft Tissue Extremity Sarcomas.

PURPOSE: Patients with large, high-grade soft tissue sarcomas are commonly treated with aggressive limb preservation regimens. This study aimed to assess cancer control outcomes of patients treated with neoadjuvant chemoradiation (CRT) compared with radiation therapy (RT) alone. METHODS: We reviewed records of patients with high-grade extremity or trunk soft tissue sarcomas ≥5 cm who were treated with neoadjuvant radiation with or without chemotherapy. Patient and disease characteristics were compared using t test and χ2 tests. Standardized mortality ratio weighted method was used to compare overall survival (OS), local control, and disease-free (DFS) survival. Acute radiation and surgical toxicity were reported. RESULTS: In the study, 64 patients (34 CRT and 30 RT) treated between 1997 and 2015 were analyzed. In the RT group compared with the CRT group, the patient population was older, with a median age of 65 versus 50 years (P < .001), and more likely to have cardiovascular disease (CVD; 30% vs 0%, P < .001). At a median follow-up of 41 months, after adjusting for propensity score of receiving RT, the 3-year LC was 87.3% versus 86.1%, DFS was 58.5% versus 56.6%, and OS was 75.6% versus 69.0% for the CRT and RT groups, respectively (P > .05). Acute dermatitis occurred in 18% versus 3% and surgical complications occurred in 32% versus 17% of CRT and RT patients, respectively. CONCLUSIONS: In this study, patients receiving RT alone were more likely to be older and have comorbid cardiovascular disease. When controlling for baseline differences, neoadjuvant CRT and RT provided similar rates of LC, DFS, and OS.

Chordoma of the sacrum and vertebral bodies.

Chordomas are relatively rare tumors of bone. These primary malignant lesions occur throughout the spinal column and often show advanced growth at the time of diagnosis. Because such tumors are minimally responsive to radiation and chemotherapy, surgical resection is the mainstay of treatment. Patient survival and local control are associated with the ability to achieve wide surgical margins during excision. However, surgical morbidity may be substantial given the propensity for chordomas to abut or surround neural, vascular, and visceral structures. Thus, early recognition is essential, and treatment by a multidisciplinary team is ideal.

Pigmented villonodular synovitis of the knee: diagnosis and treatment.

Pigmented villonodular synovitis (PVNS) of the knee is a benign but locally aggressive disease of synovial proliferation that occurs in localized nodular and diffuse villous growth patterns. Although inflammatory and neoplastic causes have been hypothesized, etiology remains unknown. Presenting as unilateral knee pain and swelling, PVNS mimics other knee ailments. Radiographs are often unremarkable, whereas magnetic resonance imaging may show characteristic intra-articular masses with signal dropout on T2-weighted sequences. Pigmented villonodular synovitis is surgically treated with open or arthroscopic total or partial synovectomy. High recurrence rates are associated with all treatments of diffuse PVNS. Complications of open synovectomy include arthrofibrosis and wound breakdown. Total arthroscopic synovectomy is technically demanding but can be advantageous. Transcondylar notch views, accessory posterior portals, and the posterior transseptal portal maximize arthroscopic access to the posterior knee. Intra-articular radioisotope injection and external beam radiation may be beneficial adjuvant therapy for extensive diffuse and recurrent PVNS of the knee.

Characterization and predictive value of volume changes of extremity and pelvis soft tissue sarcomas during radiation therapy prior to definitive wide excision.

PURPOSE: The purpose of this study was to characterize and evaluate the clinical significance of volume changes of soft tissue sarcomas during radiation therapy (RT), prior to definitive surgical resection. MATERIALS AND METHODS: Patients with extremity or pelvis soft tissue sarcomas treated at our institution from 2013 to 2016 with RT prior to resection were identified retrospectively. Tumor volumes were measured using cone-beam computed tomography obtained daily during RT. Linear regression evaluated the linearity of volume changes. Kruskal-Wallis tests, Mann-Whitney U tests, and linear regression evaluated predictors of volume change. Logistic and Cox regression evaluated volume change as a predictor of resection margin status, histologic treatment response, and tumor recurrence. RESULTS: Thirty-three patients were evaluated. Twenty-nine tumors were high grade. Prior to RT, median tumor volume was 189 mL (range, 7.2 to 4,885 mL). Sixteen tumors demonstrated significant linear volume changes during RT. Of these, 5 tumors increased and 11 decreased in volume. Myxoid liposarcoma (n = 5, 15%) predicted decreasing tumor volume (p = 0.0002). Sequential chemoradiation (n = 4, 12%) predicted increasing tumor volume (p = 0.008) and corresponded to longer times from diagnosis to RT (p = 0.01). Resection margins were positive in three cases. Five patients experienced local recurrence, and 7 experienced distant recurrence, at median 8.9 and 6.9 months post-resection, respectively. Volume changes did not predict resection margin status, local recurrence, or distant recurrence. CONCLUSION: Volume changes of pelvis and extremity soft tissue sarcomas followed linear trends during RT. Volume changes reflected histologic subtype and treatment characteristics but did not predict margin status or recurrence after resection.

Comparison of FDG-PET/CT and CT for delineation of lumpectomy cavity for partial breast irradiation.

PURPOSE: The success of partial breast irradiation critically depends on proper target localization. We examined the use of fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) for improved lumpectomy cavity (LC) delineation and treatment planning. METHODS AND MATERIALS: Twelve breast cancer patients underwent FDG-PET/CT on a GE Discovery scanner with a median time from surgery to PET/CT of 49 days. The LC was contoured on the CT scan by a radiation oncologist and, together with a nuclear medicine physician, on the PET/CT scan. The volumes were calculated and compared in each patient. Treatment planning target volumes (PTVs) were calculated by expanding the margin 2 cm beyond the LC, maintaining a 5-mm margin from the skin and chest wall, and the treatment plans were evaluated. In addition, a study with a patient-like phantom was conducted to evaluate the effect that the window/level settings might have on contouring. RESULTS: The margin of the LC was well visualized on all FDG-PET images. The phantom results indicated that the difference between the known volume and the FDG-PET-delineated volume was <10%, regardless of the window/level settings. The PET/CT volumes were larger than the CT volumes in all cases (median volume ratio, 1.68; range, 1.24-2.45; p = 0.004). The PET/CT-based PTVs were also larger than the CT-based PTV (median volume ratio, 1.16; range, 1.08-1.64; p = 0.006). In 9 of 12 patients, a CT-based treatment plan did not provide adequate coverage of the PET/CT-based PTV (99% of the PTV received <95% of the prescribed dose), resulting in substantial cold spots in some plans. In these cases, treatment plans were generated which were specifically designed to cover the larger PET/CT-based PTV. Although these plans showed an increased dose to the normal tissues, the increases were modest: the non-target breast volume receiving > or =50 Gy, lung volume receiving > or =30 Gy, and heart volume receiving > or =5 Gy increased by 5.7%, 0.8%, and 0.2%, respectively. The normal tissue dose-volume objectives were still met with these plans. CONCLUSION: The results of our study have shown that FDG-PET/CT can be used to define the LC volume. The increased FDG uptake was likely a result of postoperative inflammation in the LC. The targets defined using PET/CT were significantly larger than those defined with CT alone. Our results have shown that treatment plans can be generated to cover these larger PET/CT target volumes with only a modest increase in irradiated tissue volume compared with CT-determined PTVs.

Adjuvant concurrent chemoradiation for adenocarcinoma of the distal common bile duct.

PURPOSE: To examine the effect of adjuvant chemoradiation for adenocarcinoma of the distal common bile duct (DCBD) after pancreaticoduodenectomy (PD) on local control and survival. METHODS AND MATERIALS: A total of 34 cases of adenocarcinoma of the DCBD were treated with PD and adjuvant chemoradiation at Johns Hopkins Hospital between 1994 and 2003. Median radiation dose was 5,040 cGy (range, 4,000-5,400 cGy). Concurrent 5-fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. RESULTS: The median follow-up of patients alive at the time of analysis was 41 months. Death occurred in 21 of 34 patients (62%) during the follow-up period, all from progressive, distant metastatic disease. Median overall survival was 36.9 months, with a 5-year survival of 35%. On multivariate analysis, only nodal status significantly predicted survival (p < 0.02). For patients with negative and positive lymph nodes, 5-year survival was 100% and 24%, respectively. Actuarial 5-year local control was 70%. Compared with historical controls who underwent PD alone, patients who underwent surgery and adjuvant chemoradiation had significantly longer survival (36.9 months vs. 22 months; p < 0.05). Overall survival was significantly longer for both lymph node negative and lymph node positive patients (p < 0.05). CONCLUSIONS: Adjuvant chemoradiation after PD for adenocarcinoma of the DCBD may improve local control and overall survival. The predominant mode of failure is distant metastatic disease, highlighting the need for improved systemic therapy.

Adjuvant concurrent chemoradiation for node-positive adenocarcinoma of the duodenum.

HYPOTHESIS: Adjuvant chemoradiation improves local control and survival in patients with node-positive duodenal adenocarcinoma treated with pancreaticoduodenectomy. DESIGN: A retrospective review of outcomes, with a planned comparison with historical controls. SETTING: A single, high-volume academic referral center. PATIENTS: All patients with periampullary carcinoma treated with pancreaticoduodenectomy and adjuvant chemoradiotherapy at The Johns Hopkins Hospital between 1994 and 2003. Fourteen cases of node-positive duodenal adenocarcinoma were identified. Median radiation dose was 5000 cGy (range, 4000-5760 cGy). Concurrent fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. RESULTS: The median follow-up was 12 months for patients who died and 42 months for those who lived. Death occurred in 7 of 14 patients (50%) during the follow-up period. Median survival for all patients was 41 months, and the 5-year survival rate was 44%. Of the 7 patients who experienced disease recurrence, 6 experienced distant metastasis as first recurrence. One of these 7 patients experienced both local recurrence and distant metastasis. Local control for all patients in the study was 93%, which compares favorably with local control reported in a series of patients treated with surgery alone (67%). Compared with historical controls treated with surgery alone, patients who received adjuvant chemoradiation therapy had an improved median survival (21 months vs 41 months, respectively). Overall 5-year survival, however, was not improved (44% vs 43%, respectively). CONCLUSION: Adjuvant chemoradiation therapy after pancreaticoduodenectomy for node-positive duodenal adenocarcinoma may improve local control and median survival but does not impact 5-year overall survival.

Proximal femoral replacement for metastatic bone disease.

Between 1994 and 2000, 13 patients (8 women and 5 men; 14 hips) underwent proximal femoral replacement secondary to metastatic disease. Average patient age was 62 years (range: 46-77 years). The most common diagnosis was renal cell carcinoma. Seven pathologic fractures were noted. Patients ambulated with full weight bearing postoperatively and wore an abduction brace for 3-4 months. Ten patients died of their diseases at 0.5-3.5 years postoperatively. No dislocations, infections, or reoperations occurred. Proximal femoral replacement provides excellent pain relief and good restoration of function when more simple reconstructive options are not feasible.

Preoperative versus postoperative radiation therapy for soft-tissue sarcomas.

In this article, we report results from a retrospective consecutive series of 117 patients with soft-tissue sarcomas treated with adjuvant radiation and surgical resection at 2 associated institutions. Fifty-nine patients received preoperative radiation; 58 patients received postoperative radiation. Mean clinical follow-ups were 6.1 years and 8.4 years, respectively. Nineteen (32.2%) of 59 patients in the preoperative group and 17 (29.3%) of 58 patients in the postoperative group had wound complications (P = .89). Three (5.1%) of 59 sarcomas in the preoperative group and 7 (12.1%) of 58 sarcomas in the postoperative group recurred locally (P = .19). Improved local disease control and other potential advantages of using preoperative radiation make this a preferred adjuvant treatment.

Treatment of complications after breast-conservation therapy.

Over the past 2 decades, breast-conservation therapy with lumpectomy and whole-breast radiotherapy has become a standard option for the majority of women with newly diagnosed breast cancer. Long-term local control is achieved in approximately 85% of patients, and the therapy is generally well tolerated. There can, however, be long-term effects on the breast and other nearby tissues that may range from asymptomatic findings on examination to severe, debilitating problems. Infection, fat necrosis, and severe musculoskeletal problems such as osteoradionecrosis or soft-tissue necrosis are uncommon, affecting less than 5% of patients. However, changes in range of motion, mild-to-moderate musculoskeletal pain, and arm and breast edema are much more common. As more women choose breast-conservation therapy for management of their breast cancer, physicians will encounter these problems, as well as in-breast tumor recurrence, with greater frequency. This review will focus on the incidence, contributing factors, and management of the late problems of infection, fat necrosis, musculoskeletal complications, and local recurrence following breast-conservation therapy.

Metastatic bone disease of the humerus.

Metastatic bone disease is the most common cause of destructive bone lesions in adults, and involvement of the humerus is common. Patients with destructive lesions involving <50% of the cortex are treated nonsurgically with external beam irradiation. Patients with diaphyseal lesions involving > or =50% of the cortex or those with pain after irradiation can be treated with intramedullary nailing to achieve rigid fixation. Although closed intramedullary nailing is used most often, open nailing with methylmethacrylate is appropriate for destructive lesions in which rigid fixation cannot be achieved with closed nailing. Plate fixation is acceptable when adequate proximal and distal cortical bone is present for screw purchase, although proximal humeral lesions usually are treated with prosthetic arthroplasty. Postoperative external beam irradiation can help prevent disease progression and subsequent loss of fixation. However, when disease progression persists or rigid internal fixation is not feasible because of extensive bone destruction, wide resection and reconstruction with a custom prosthesis can be done.

The role of radiation treatment in the contemporary management of bone tumors.

Radiotherapy is integral in the multidisciplinary approach to patients with musculoskeletal neoplasms. Multiple studies have established a role for radiotherapy as a definitive local treatment of unresectable lesions or when surgery might yield unacceptable functional outcomes, such as in Ewing's tumor or base of skull chondrosarcoma. Radiotherapy is also used as an adjuvant treatment after surgery with close or positive margins. In the metastatic setting, external beam radiotherapy and bone-seeking intravenous radioisotopes are used on a case-by-case basis for palliation. As radiotherapy and its delivery techniques have evolved, so has its role in treating tumors such as Ewing's sarcoma, chordoma and chondrosarcoma, osteosarcoma, primary lymphoma of bone, malignant fibrous histiocytoma of bone, and vascular tumors. Radiation can also be successfully used to treat unresectable or recurrent benign tumors, such as giant cell tumor and aneurysmal bone cyst. This article reviews the indications for radiotherapy for various bone tumors and summarizes some of the important data supporting its use.

Perineural invasion affects biochemical recurrence-free survival in patients with prostate cancer treated with definitive external beam radiotherapy.

OBJECTIVES: To assess the prognostic effect of perineural invasion (PNI) for patients undergoing external beam radiotherapy for prostate cancer. METHODS: We evaluated 657 consecutive patients who had undergone external beam radiotherapy for clinically localized prostate cancer. The clinical/treatment parameters used for analysis included PNI, clinical stage, biopsy Gleason score, pretreatment prostate-specific antigen, radiation dose, and androgen deprivation. The primary endpoint was biochemical recurrence defined by the Radiation Therapy Oncology Group-American Society for Therapeutic Radiology Oncology Phoenix consensus; the secondary endpoint was prostate cancer death. RESULTS: Of 586 men with a minimum of 24 months of follow-up, 112 (19.1%) had PNI present in the biopsy specimen. When patients were stratified into risk groups using the National Comprehensive Cancer Network criteria, PNI was more prevalent in patients within higher risk groups (6.8% in low-risk versus 18.3% in intermediate-risk versus 30.1% in high-risk groups; P <0.001). The presence of PNI was associated with lower biochemical recurrence-free (P = 0.003) and cancer-specific (P = 0.040) survival rates by Kaplan-Meier analysis. Cox regression analysis showed that PNI was a statistically significant prognostic factor of biochemical recurrence on both univariate (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.19 to 2.46, P = 0.004) and multivariate (HR 1.57, 95% CI 1.06 to 2.32, P = 0.025) analyses. Regression analysis after stratification by risk group and adjustment for treatment covariates demonstrated a significant association between PNI and the risk of biochemical recurrence for low-risk (HR 4.14, 95% CI 1.55 to 11.02, P = 0.005) and intermediate/high-risk patients (HR 1.53, 95% CI 1.02 to 2.29, P = 0.040). CONCLUSIONS: The results of our study have shown that the presence of PNI is an independent risk factor associated with an increased risk of biochemical recurrence in patients with prostate cancer undergoing external beam radiotherapy.

Outcomes of re-excision after unplanned excisions of soft-tissue sarcomas.

BACKGROUND AND OBJECTIVES: Unplanned excisions of soft-tissue sarcomas of the extremities occur commonly. Our goal was to evaluate the presence of residual disease, the treatment outcomes as they relate to local and distant recurrence and 5-year survival, and the limb functional outcomes in patients with unplanned sarcoma excision who were treated with re-excision and adjuvant therapy. METHODS: Between 1993 and 1999, 42 patients presented to our institution after unplanned excision of soft-tissue sarcomas. Of those 42 patients, 38 without gross residual disease or metastatic lesions formed the basis of this review. All 38 patients underwent revision wide excision; most (31) also received adjuvant therapy (radiation and/or chemotherapy). Clinical data were obtained from analysis of patient records and radiographic studies. Univariate analysis was performed with logistical regression, and multivariate analysis was performed with Cox modeling. RESULTS: The overall 5-year survival rate was 91.3% and the disease-free 5-year survival rate was 82.2%. Univariate analysis showed that stage-III disease (American Joint Committee on Cancer classification of soft-tissue sarcomas), lesions below the fascia, a histologic high-grade, and the development of organ metastasis were statistically significant factors for mortality. Stage-III disease also was significant for mortality on multivariate analysis. Only stage-III disease was significant for the development of local recurrence. Eighty-four percent of the patients had good to excellent functional outcomes. CONCLUSIONS: Re-excision with adjuvant therapy proved to be a safe and effective method for treating the disease and preserving limb function.

General principles of external beam radiation therapy for skeletal metastases.

Radiation therapy plays a major role in the treatment of patients with bone metastases. The primary goals of treatment include pain relief and relief of neurologic symptoms, if present. Approximately 70% of patients will achieve pain relief with palliative external beam radiotherapy. Improvement in the severity of pain may occur within as few as 48 to 72 hours of initiation of therapy, but in some patients significant relief of pain may not occur for 4 weeks after completion of therapy. Treatment schemes ranging from 800 cGy in a single treatment to 3000 cGy in 10 treatments have not been shown to result in major differences in outcome. Treatment decisions must be individualized based on factors such as the patient's performance status, life expectancy, location of the lesion, and size of area to be treated. External beam radiotherapy is recommended after surgical treatment of pathologic fractures or impending fractures to decrease the need for a second surgical procedure and improve the patient's functional outcome. External beam radiotherapy continues to be an important component of the palliative treatment of bone metastases. Its integration with newer therapeutic modalities such as vertebroplasty and radiofrequency ablation currently is being studied.

Evaluation and treatment of metastases to the humerus.

The humerus is the second most common long bone site of metastatic disease, and the proximal third and diaphysis are frequent sites. Purely lytic disease and cortical bone destruction increase the risk of fracture more than 50%. For most patients, external beam irradiation is effective as a means of pain control and halting bone destruction. Fractures of the head or surgical neck can be treated with standard endoprostheses, whereas extensive proximal bone destruction is treated with custom proximal humeral replacements. Impending and complete diaphyseal fractures can be treated effectively with either intramedullary nail fixation or plate fixation. Rigid fixation, which can be achieved with dual plate fixation, is optimal because patients can begin immediate unrestricted activities using the upper extremity. Methylmethacrylate is an effective adjuvant for filling defects and for augmenting the fixation of intramedullary nails and screws. Postoperative external beam irradiation is necessary to prevent progressive bone destruction and subsequent loss of fixation.

Radiation oncology: the year in review.

Radiotherapy plays an essential role in the treatment of patients with breast cancer. The literature in English dealing with radiation therapy in the management of breast cancer published between May 2001 and April 2002 was reviewed. A variety of articles were chosen by the authors to be presented in this review. The areas of particular interest include the role of boost therapy after whole-breast irradiation, the use of intraoperative irradiation after lumpectomy, the management of ductal carcinoma the effect of age on outcome of therapy, and side-effects of irradiation. Space does not allow a comprehensive review of all the published literature, but the articles chosen were thought to be of special interest to those involved in breast cancer management.