Ivy A. Petersen

Percutaneous Image-Guided Radiofrequency Ablation of Painful Metastases Involving Bone: A Multicenter Study

PURPOSE Few options are available for pain relief in patients with bone metastases who fail standard treatments. We sought to determine the benefit of radiofrequency ablation (RFA) in providing pain relief for patients with refractory pain secondary to metastases involving bone. PATIENTS AND METHODS Thirty-one US and 12 European patients with painful osteolytic metastases involving bone were treated with image-guided RFA using a multitip needle. Treated patients had > or = 4/10 pain and had either failed or were poor candidates for standard treatments such as radiation or opioid analgesics. Using the Brief Pain Inventory-Short Form, worst pain intensity was the primary end point, with a 2-unit drop considered clinically significant. RESULTS Forty-three patients were treated (median follow-up, 16 weeks). Before RFA, the mean score for worst pain was 7.9 (range, 4/10 to 10/10). Four, 12, and 24 weeks following treatment, worst pain decreased to 4.5 (P <.0001), 3.0 (P <.0001), and 1.4 (P =.0005), respectively. Ninety-five percent (41 of 43 patients) experienced a decrease in pain that was considered clinically significant. Opioid usage significantly decreased at weeks 8 and 12. Adverse events were seen in 3 patients and included (1) a second-degree skin burn at the grounding pad site, (2) transient bowel and bladder incontinence following treatment of a metastasis involving the sacrum, and (3) a fracture of the acetabulum following RFA of an acetabular lesion. CONCLUSION RFA of painful osteolytic metastases provides significant pain relief for cancer patients who have failed standard treatments.

INITIAL EFFICACY RESULTS OF RTOG 0319: THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY (3D-CRT) CONFINED TO THE REGION OF THE LUMPECTOMY CAVITY FOR STAGE I/ II BREAST CARCINOMA

PURPOSE This prospective study (Radiation Therapy Oncology Group 0319) examines the use of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Initial data on efficacy and toxicity are presented. METHODS AND MATERIALS Patients with Stage I or II breast cancer with lesions < or =3 cm, negative margins and with < or =3 positive nodes were eligible. The 3D-CRT was 38.5 Gy in 3.85 Gy/fraction delivered 2x/day. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Mastectomy-free, disease-free, and overall survival (MFS, DFS, OS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, was used to grade acute and late toxicity. RESULTS Fifty-eight patients were entered and 52 patients are eligible and evaluable for efficacy. The median age of patients was 61 years with the following characteristics: 46% tumor size <1 cm; 87% invasive ductal histology; 94% American Joint Committee on Cancer Stage I; 65% postmenopausal; 83% no chemotherapy; and 71% with no hormone therapy. Median follow-up is 4.5 years (1.7-4.8). Four-year estimates (95% CI) of efficacy are: IBF 6% (0-12%) [4% within field (0-9%)]; INF 2% (0-6%); CBF 0%; DF 8% (0-15%); MFS 90% (78-96%); DFS 84% (71-92%); and OS 96% (85-99%). Only two (4%) Grade 3 toxicities were observed. CONCLUSIONS Initial efficacy and toxicity using 3D-CRT to deliver APBI appears comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate the extent of application, limitations, and value of this particular form of APBI.

USE OF INTRAOPERATIVE ELECTRON BEAM RADIOTHERAPY IN THE MANAGEMENT OF RETROPERITONEAL SOFT TISSUE SARCOMAS

PURPOSE To evaluate the disease control, survival results, and tolerance of intraoperative electron beam radiotherapy (IOERT) as a component of treatment for retroperitoneal soft tissue sarcomas. METHODS AND MATERIALS Between March 1981 and September 1995, 87 patients with primary (n = 43) or recurrent (n = 44) retroperitoneal or intrapelvic sarcomas received IOERT as a component of treatment at the Mayo Clinic. The tumors were high grade in 54 patients (62%) and low grade in 33 (38%). The median tumor size was 10 cm (range 2-36). All patients underwent maximal surgical resection with IOERT; in 72 patients, only microscopic or no residual tumor remained. The IOERT doses ranged from 8.75 to 30 Gy (median 15). All primary tumors received external beam irradiation (EBRT) with a median dose of 48.6 Gy. Thirty-four of the 44 recurrent tumors received EBRT to a median dose of 45 Gy. All patients were followed prospectively for outcome and toxicity evaluation. RESULTS The median follow-up, based on 46 patients (53%) currently alive, was 3.5 years. The overall estimated 5-year survival was 47%. For patients with tumors > or = 10 cm, the 5-year overall survival was significantly poorer (28%) than for those with smaller lesions (60%) (p = 0.01). Neither primary vs. recurrent status nor tumor grade had a significant impact on survival. Patients with gross residual tumor had a marginally significantly poorer survival compared with patients with microscopic or no residual tumor, with a 5-year survival rate of 37% and 52%, respectively (p = 0.08). A total of 49 patients (56%) experienced failure, including 20 local recurrences (23%). The median time to failure was 2.3 years. Four recurrences were within the IOERT field, 3 within the IOERT and EBRT field, and 13 within the EBRT field alone. The 3- and 5-year estimated local control rate was 77% and 59%, respectively. Local control was marginally significantly affected by the amount of residual tumor, with a 5-year local control rate of 41% for those with gross residual tumor, 60% for those with microscopic residual tumor, and 100% for those with no residual tumor (p = 0.09). Gastrointestinal complications were recorded in 12 incidences (Grade 3 or higher toxicity). These complications were believed to be secondary to surgery and/or EBRT in 10 of the 12 cases. Seven patients had fistula formation, and 3 experienced severe proctitis. Grade 3 peripheral neurologic toxicities occurred in 9 patients (10%), but none had pain as a component of their neuropathy. CONCLUSION Retroperitoneal soft tissue sarcomas can be treated with an aggressive combined approach of EBRT, surgery, and IOERT, with acceptable toxicity. Local control in primary disease appears to be improved in this retrospective series with this approach. Distant disease control and options for recurrent disease needs further definition.

Local control of extra-abdominal desmoid tumors.

We analyzed the records and histopathological specimens of fifty patients who had had a previously untreated desmoid tumor. The patients were followed for at least two years (average, forty-eight months). Three patients had a biopsy and were managed with observation only, and three patients had radiation therapy only. Of the remaining forty-four patients, thirty-four were managed with an operation and ten, with an operation and radiation therapy. In the group that was managed operatively without radiation therapy, the resection was wide in thirteen patients, marginal in nineteen, and intralesional in two. At the most recent follow-up examination, there had been no local recurrence in eleven of the patients who had had a wide resection, ten of the patients who had had a marginal resection, and one of the patients who had had an intralesional resection. Thus, twenty-two (65 per cent) of the thirty-four patients had no local recurrence at the time of the latest follow-up. In the group of ten patients who had been managed with an operation and radiation therapy, eight had no local recurrence: the two who had had a wide resection, three of the four who had had a marginal resection, and three of the four who had had an intralesional resection. None of the fifty patients died of the disease.

The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas

PURPOSE This report presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND MATERIALS Members of the ABS with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS Brachytherapy used alone or in combination with external beam irradiation is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas in adults and in children. Brachytherapy options include low dose rate techniques with iridium 192 or iodine 125, fractionated high dose rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are made for patient selection, techniques, dose rates, and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed. CONCLUSION Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biologic and dosimetric advantage in the treatment of patients with soft tissue sarcoma. The treatment approach used depends upon the institution, physician expertise, and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas in adults and in children. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as further clinical results become available.

Clinicopathologic features and treatment of postirradiation sarcoma of bone and soft tissue.

An analysis of the clinicopathologic features and treatment of patients with postirradiation sarcoma of bone and soft tissue was performed to guide modern evaluation and management.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Primary and secondary angiosarcoma of the breast: the Mayo Clinic experience.

Angiosarcoma of the breast can be divided into primary and secondary. The objective was to determine clinicopathologic factors associated with breast angiosarcoma and to compare primary versus secondary angiosarcoma.

Comparison and consensus guidelines for delineation of clinical target volume for CT- and MR-based brachytherapy in locally advanced cervical cancer

OBJECTIVE To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. METHODS AND MATERIALS Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. RESULTS For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. CONCLUSION In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx.

Ductal Carcinoma in Situ of the Breast

Ductal carcinoma in situ (DCIS) of the breast is a complex pathologic condition in which malignant breast epithelial cells arise and proliferate in the ducts but do not invade the surrounding stroma. As options for the primary treatment of invasive breast cancer have broadened to include breast-conserving therapy, continued use of mastectomy as standard care for DCIS has been questioned [1]. The increasing incidence of DCIS, its biological heterogeneity, and controversy about its treatment have made the management of this condition challenging. We review data on the natural history of this disorder and the results obtained with various management approaches. Specifically, we address the following points: the incidence of DCIS, the classification of the condition, the molecular genetic abnormalities associated with it, its usual clinical presentation, its natural history, the proportion of lesions that are multicentric, the treatment options, whether axillary lymph node dissection should be performed, whether all patients need radiotherapy if they undergo lumpectomy, the survival rates associated with these treatments, the risk factors for recurrence, the best treatment for recurrence, and the possible role of hormonal therapy. Methods We performed a computerized search of the MEDLINE database for English-language articles on DCIS of the breast published since 1966. The search was done by using the words carcinoma in situ, ductal carcinoma in situ, intraductal breast cancer, and DCIS. References in the identified articles were reviewed. Because randomized trials were given higher value but were relatively scarce, retrospective studies were also reviewed. In addition, published abstracts were reviewed, but no personal communications and case reports were considered. The authors reviewed all sources critically but conducted no formal statistical analyses. Data Synthesis Biology and Natural History Incidence The exact incidence of DCIS in the general population is unknown and has been a source of controversy. In an autopsy study of 519 women of various ethnic backgrounds, only one case (0.2%) of DCIS was found (in a woman who died at 40 years of age) [2]. Of these 519 women, only 117 were older than 55 years of age. Alpers and Wellings [3] performed autopsies on 185 patients, of whom 9 (4.9%; 11 breasts) had evidence of the tumor on subgross sampling (which involves cutting breast tissue into 2-mm slices, examining the slices with a dissecting microscope, and evaluating any focal lesion [4]). The findings of the autopsy studies suggest that incidental DCIS of uncertain clinical relevance is not common. Variations in incidence among autopsy studies probably reflect differences in sampling techniques and diagnostic criteria. Ductal carcinoma in situ of the breast also occurs in men and represents 3.5% to 7% of all cases of male breast cancer [5, 6]. The incidence of DCIS has increased in recent years, partly because screening mammography is more refined and more widely used [7-10]. In 1992, DCIS was diagnosed in more than 23 300 women (age-adjusted incidence rate, 15.9 per 100 000 women) [11]. The rate of increase in incidence has been higher for DCIS than for any other type of breast cancer [12]. The reported incidence in women 50 years of age or older increased 235% from 1979 to 1986; in contrast, the incidence of invasive cancer increased 50% [13]. However, mammography alone does not seem to explain the increasing incidence of DCIS. Data from the metropolitan Atlanta Surveillance, Epidemiology, and End Results (SEER) study (1979 to 1986) showed that asymptomatic tumors (those detected on screening mammography alone) accounted for only 25% to 40% of the increase in incidence [14]. These reports suggest that increased detection accounts for some but not all of the increase in incidence. The National Cancer Institute SEER data for the entire United States confirmed this trend [11]. Overall, the total number of cases of DCIS in 1992 was 200% greater (23 368 cases) than expected for that year as calculated from the trends between 1973 and 1983. Pathology Ductal carcinoma in situ is a heterogeneous entity with several morphologic variants that markedly differ in gross appearance, growth pattern, and cytologic features. Furthermore, it is part of a spectrum of proliferative ductal lesions of the breast that extends from epithelial hyperplasia without atypia to microinvasive carcinoma. Various classification schemes for DCIS exist. Most pathologists and clinicians recognize two major subtypes of DCIS according to the presence or absence of comedo necrosis, but this is a matter of considerable debate. These two subtypes differ not only in pathologic features but also in clinical presentation, appearance on mammography, and malignant potential. The comedo necrosis type of DCIS is diagnosed when at least one duct in the breast is filled and expanded by large, markedly atypical cells and has abundant central luminal necrosis (Figure 1). This necrotic material is usually partially calcified and thus may be recognized on mammography as linear and branching calcifications. Prominent periductal fibrosis is common and may render the lesion clinically palpable. The resulting distortion of the breast parenchyma may present the pathologist with the difficult and sometimes impossible task of excluding stromal invasion. Figure 1. Comedo necrosis ductal carcinoma in situ. All other forms of DCIS are of the noncomedo necrosis type and include the cribriform, micropapillary, and solid types (Figure 2). Many examples of the noncomedo necrosis type consist of a combination of the various histologic patterns. Although necrosis may be present, it is less prominent than in the comedo necrosis type and is not as prone to calcification. Just as the comedo necrosis type may overlap with microinvasive carcinoma, distinguishing small examples of the noncomedo necrosis type from atypical ductal hyperplasia may be difficult. However, if careful attention is paid to standardized diagnostic criteria, this distinction can be made with reasonable certainty [15-17]. Figure 2. Noncomedo necrosis ductal carcinoma in situ. Many pathologists think that the comedo necrosis-noncomedo necrosis classification scheme is too simplistic and does not account for the marked heterogeneity of DCIS. This has led to several new classification schemes for DCIS [18-21]. All of these schemes take into account some or all of the following features: nuclear grade, amount and type of necrosis, growth pattern, tumor size, and architectural differentiation. The optimal classification scheme remains controversial. Molecular Genetics and Cytogenetic Studies Little information is available on chromosomal abnormalities in DCIS [22]. With the use of interphase cytogenetic techniques, 18 of 21 (86%) samples of the tumor were aneusomic for chromosome 1 [23]. In another study, aneuploidy, as determined by image analysis, was seen in 77.5% of cases of the tumor, mainly in the high- and intermediate-grade subtypes [24]. Specimens of DCIS have several alterations at the molecular genetic level. Overexpression of c-erbB-2 occurs in 46% to 60% of cases; the frequency is higher with the comedo necrosis type. In contrast, this overexpression is seen in only 20% to 25% of cases of invasive breast cancer [25-30]. At least some cases of invasive breast cancer that express c-erbB-2 seem to be derived from preexisting DCIS [31]. Maguire and colleagues [31] studied 12 specimens containing the noncomedo necrosis type and derivative invasive adenocarcinomas in the same section, all of which were negative for c-erbB-2 expression. However, of 13 comedo necrosis carcinomas in situ with an invasive component, 10 had definite c-erbB-2 expression that was similar in the in situ and invasive components in every case. Mutations of the p53 gene are present in DCIS and are more common in the comedo necrosis type [32]. Allelic imbalance (loss of intensity of one allele) for the BRCA1 gene has been found in 74% of cases of the tumor [33]. Loss of heterozygosity has been described in the tumor at loci reported to show allelic loss in invasive breast cancers [34]. Identical loss of heterozygosity in the in situ component of tumors with invasive tumor cells has been reported on chromosome 11q13 [35], further supporting the idea that the tumor is preinvasive. Over-expression of cyclin D1, an oncogene on 11q13, is present in nearly 90% of malignant breast lesions (both DCIS and invasive breast cancer) [36]. Although some molecular genetic data support the hypothesis that invasive breast cancer can arise from preexisting in situ lesions, this has not been definitively proven. More work is needed to broaden our understanding of the relation between DCIS and invasive breast cancer. Clinical Presentation Ductal carcinoma in situ can present clinically as a palpable mass; Paget disease (which may be diagnosed independently); nipple discharge; or, most commonly, a nonpalpable abnormality on mammography [37]. It now accounts for 20% to 30% of all newly diagnosed cases of breast cancer in medical centers where screening is standard [38]. The most frequent radiologic finding is a collection of malignant-appearing or indeterminate calcifications [39], often with no other associated abnormalities. In our experience with nonpalpable lesions seen on mammography, 22% of indeterminate calcifications alone are associated with a histologic diagnosis of malignancy; 76% of these are minimal cancers, and almost all are DCIS [40]. Of all malignant-appearing calcifications, 92% are associated with a malignant histologic diagnosis. Fifty-eight percent of these are minimal cancers, and most are DCIS [40]. In addition, atypical features may include circumscribed nodules, ill-defined masses, ductal asymmetry, architectural distortion, and negative findings on mammography [41]. In a review of 100 mammographically detected cases of DCIS, 72% pr