Radiation-Induced Sarcoma: A Challenge for the Surgeon

Background Treatment of radiation-induced sarcoma (RIS) remains an unsolved problem. To provide more insight into the disease process, its characteristics, outcome, and potential outcome determinants were defined.Methods From 1978 to 2003, 27 patients—20 females (74%) and 7 males (26%) with a median age 44 years (range, 1–73 years) at the time of diagnosis of the primary tumor—developed an RIS after a median interval of 8 years (range, 3–41 years). The histology of the RIS was 10 (37%) undifferentiated high-grade pleomorphic sarcomas, 7 (26%) angiosarcomas, 6 (22%) fibrosarcomas, 2 (7%) osteosarcomas, 1 (4%) pleomorphic rhabdomyosarcoma, and 1 (4%) pleomorphic leiomyosarcoma. Surgical resection was performed in 21 patients: 13 (62%) R0 (microscopically radical), 4 (19%) R1 (microscopically irradical), 2 (9.5%) R2 (macroscopically irradical), and 2 (9.5%) RX (unknown radicality). Six (22%) patients underwent no resection.Results The 5-year disease-free and overall survival rates were 27% and 30%, respectively. The local failure rate after R0 resection was 54%. The distant failure rate for the entire group was 41%. Patients with an R0 resection had a significantly better survival rate (P < .05) than patients with an R1, R2, or no resection.Conclusions RISs are aggressive malignancies with a high tendency for local recurrence and distant metastases. Previously applied treatment often hampers adequate resection. Therefore, radical surgical resection is the only chance to improve disease-free and overall survival, but it may also have a palliative role. Still, the overall prognosis remains poor.     

Hemangiopericytoma: A 20-year single-institution experience

Background: Hemangiopericytoma is an uncommon soft tissue sarcoma. We sought to evaluate the long-term outcome of a consecutively treated patient cohort with hemangiopericytoma. Methods: The study involved 36 adult patients (older than 16 years) with hemangiopericytoma treated at The University of Texas M. D. Anderson Cancer Center between July 1975 and July 1995. Data on clinicopathologic parameters, surgical treatment, adjuvant therapy, disease recurrence, and survival were obtained from a review of medical records. Results: The median follow-up was 57 months. Twenty-eight patients (78%) underwent complete and potentially curative resection of their primary disease. Of the nine patients (32%) who had local recurrences, four (57%) had epidural tumors and three (43%) had retroperitoneal tumors, but none had extremity tumors. Extremity tumors were associated with a significantly prolonged local recurrence-free survival compared to tumors at nonextremity anatomic sites (P<.05). Ten patients had recurrences at distant sites. Of the 13 patients who experienced any form of disease recurrence, four had recurrences after a disease-free interval of more than 5 years. The 5-year actuarial survival rate for the entire group of 36 patients was 71%. Noncurative surgical treatment (P=.007) and development of distant metastatic disease (P=.013) were associated with shortened survival. Conclusion: Extended survival is common in hemangiopericytoma patients treated with curative intent. However, local and distant recurrences may occur after a prolonged disease-free interval, emphasizing the need for long-term follow-up. Retroperitoneal and meningeal tumors were associated with higher local recurrence rates; therefore, adjuvant therapies should be considered and evaluated for tumors at these sites. Presented at the 48th Annual Meeting of the Society of Surgical Oncology, Boston, Massachusetts, March 1995.     

Changes in breast cancer management during the Corona Virus Disease 19 pandemic: An international survey of the European Breast Cancer Research Association of Surgical Trialists (EUBREAST)

BackgroundCorona Virus Disease 19 (COVID-19) had a worldwide negative impact on healthcare systems, which were not used to coping with such pandemic. Adaptation strategies prioritizing COVID-19 patients included triage of patients and reduction or re-allocation of other services. The aim of our survey was to provide a real time international snapshot of modifications of breast cancer management during the COVID-19 pandemic.MethodsA survey was developed by a multidisciplinary group on behalf of European Breast Cancer Research Association of Surgical Trialists and distributed via breast cancer societies. One reply per breast unit was requested.ResultsIn ten days, 377 breast centres from 41 countries completed the questionnaire. RT-PCR testing for SARS-CoV-2 prior to treatment was reported by 44.8% of the institutions. The estimated time interval between diagnosis and treatment initiation increased for about 20% of institutions. Indications for primary systemic therapy were modified in 56% (211/377), with upfront surgery increasing from 39.8% to 50.7% (p < 0.002) and from 33.7% to 42.2% (p < 0.016) in T1cN0 triple-negative and ER-negative/HER2-positive cases, respectively. Sixty-seven percent considered that chemotherapy increases risks for developing COVID-19 complications. Fifty-one percent of the responders reported modifications in chemotherapy protocols. Gene-expression profile used to evaluate the need for adjuvant chemotherapy increased in 18.8%. In luminal-A tumours, a large majority (68%) recommended endocrine treatment to postpone surgery. Postoperative radiation therapy was postponed in 20% of the cases.ConclusionsBreast cancer management was considerably modified during the COVID-19 pandemic. Our data provide a base to investigate whether these changes impact oncologic outcomes.     

Extremity Soft Tissue Sarcoma: Adding to the Prognostic Meaning of Local Failure

Background We explored the prognostic meaning of local relapse and surgical margins in adult soft tissue sarcoma of the extremities. Methods Out of a series of 1017 patients with extremity soft tissue sarcoma treated over 20 years, we picked a group of 238 patients operated on at our institution for their first local relapse: 88 after their primary operation performed at the same center and 150 elsewhere. At operation for relapse, margins were microscopically negative in 77% and 75% of patients, respectively. Median follow-up was 107 months. Results The 10-year mortality rate was 22% in the absence of local relapse, whereas in locally relapsing patients it was 54% and 43%, respectively, for patients first operated on at our institute and for those who were not. The hazard ratio of positive versus negative surgical margins was 1.7 for cause-specific death and 2.1 for distant metastases in patients first operated on at our institute, as opposed to 1.2 and 1.3 for the others. Conclusions Local relapse was an unfavorable prognostic factor. In the face of a consistent surgical policy for local relapse in a single-institution setting, patients relapsing after the first operation performed at our institution received rescue treatment less frequently than those previously operated on outside a referral center. This is likely due to an inherently higher tumor aggressiveness. In the presence of such a higher aggressiveness, the adequacy of surgical margins at operation for first relapse seemed more critical prognostically. This may have clinical and speculative implications. Presented at the Annual Meeting of the American Society of Clinical Oncology, June 2–6, 2006, Atlanta, GA (USA) (abstract 9565).     

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Background Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17–159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50–1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91–1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1–23.9 vs. median, 7.35; range, 4.8–21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0–21.4 vs. median, 10.95; range, 8.0–32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity. Presented at the 59th Annual Cancer Symposium, Society of Surgical Oncology, San Diego, CA, 2006.     

Post-treatment sarcoma in breast cancer patients

Background: Many patients treated for breast cancer with radiotherapy will survive their disease and be at risk for treatment-related sarcoma for many years. Methods: In order to identify patients with post-treatment sarcoma and define this disease, we examined the records of 99 patients treated for sarcoma with a history of antecedent breast carcinoma. Of these patients, 51 were felt to have a sarcoma unrelated to breast cancer treatment and 48 were felt to have a treatment-related sarcoma (secondary to lymphedema and/or radiation). Results: Lymphangiosarcoma of the extremity was the most common histologic subtype of post-treatment sarcoma, accounting for 22 of 48 cases (46%). Twenty-six patients (54%) developed nonlymphangiosarcoma post-treatment sarcoma; all of these were radiation-associated sarcomas. The median latency interval between the diagnosis of breast cancer and the development of sarcoma was 11 years (range 4–44) and was not different between the two groups. However, patients with nonlymphangiosarcoma were significantly younger when diagnosed with breast cancer than were those with lymphangiosarcoma of the extremity (median 43 vs. 51 years, p<0.001). The survival of all 48 patients was poor: 5-year survival was 29%. Five-year survival of patients with other types of post-treatment sarcoma was just as poor as those with lymphangiosarcoma of the extremity (30% vs. 28%, p=0.98). Conclusions: Patients who develop sarcoma after treatment for breast cancer have a poor prognosis whether it occurs as Stewart-Treves syndrome or other types of post-treatment sarcoma. Younger patients may be at higher risk than are older patients for the development of nonlymphangiosarcoma post-treatment sarcoma.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

Leiomyosarcoma of the Inferior Vena Cava: Survival After Aggressive Management

Background Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is exceedingly rare. The role of adjuvant therapy remains undefined. This study evaluated outcomes after aggressive management. Methods Records on 20 patients undergoing surgery for IVC LMS between January 1990 and April 2006 were retrieved. Histology was confirmed upon re-review. Most patients received perioperative chemotherapy (CT), radiation therapy (RT), or both (CRT). Disease-free and overall survival (DFS, OS) rates were calculated using the Kaplan-Meier method. Results Twenty patients (60% women, median age 57 years) with primary IVC LMS were treated with curative intent. Median follow-up was 41 months. All patients underwent resection of the primary tumor; one was found to have unresectable liver metastases. The IVC was managed with ligation (3), primary repair (12), or prosthetic graft (5). Additional organs were resected in 14 (70%) patients. Chemotherapy and/or RT were administered to 9 (45%) patients preoperatively (CT 2, RT 6, CRT 1) and 8 (40%) postoperatively (CT 4, RT 1, CRT 3). Median DFS was 21 months. Of 13 (68%) patients who developed recurrence, 4 underwent surgery, and 11 received CT. Median OS for 19 patients who underwent complete resection was 71 months. Tumor size was associated with disease recurrence (P = .004). No variables were prognostic for OS. Conclusions Patients with IVC LMS treated with curative intent develop early recurrent disease. Nevertheless, long-term OS can be achieved even in the setting of metastatic disease. The independent impact of perioperative CT, RT, or CRT treatments cannot be adequately determined. Presented at the 60th Annual Meeting of Society of Surgical Oncology, March 15, 2007 to March 18, 2007, Washington, D.C.     

乳腺癌术后放疗诱发性肉瘤的治疗进展

【摘要】〓放疗诱发性肉瘤(radiation induced sarcoma, RIS)是一种罕见的、恶性程度较高的肿瘤,可发生于乳腺癌、妇科肿瘤、霍奇金淋巴瘤和其他类型肿瘤放射治疗后,而其中乳腺癌放疗诱发性肉瘤占较大的比例。目前,对于此类肿瘤的治疗仍是临床上一大难题,不管是手术治疗还是手术联合辅助放化疗,其5年生存率仍较低,且治疗后局部复发率很高。为提高临床医生对放疗诱发性肉瘤治疗方案的优化选择,改善患者预后,本文对目前针对放疗诱发性肉瘤的治疗进展做一综述。     

Phyllodes tumour with heterologous sarcomatous differentiation: Case series with literature review

IntroductionPhyllodes tumours are rare fibroepithelial malignancies of the breast, accounting for less than 1% of malignant breast tumours. Further malignant differentiation of phyllodes tumours can occur, resulting in cases of extremely rare heterologous sarcomatous differentiation.Presentation of caseTwo females in their fifties were diagnosed with malignant phyllodes tumour associated with heterologous sarcomatous differentiation. The first patient, aged 50 had phyllodes tumour with chondrosarcoma, osteosarcoma and ductal carcinoma-in-situ. The second patient, aged 53 had phyllodes tumour with osteosarcoma and liposarcoma.DiscussionThe association of phyllodes tumour and heterologous sarcomatous differentiation is rare, with only 4 previously reported cases in English literature. The paucity of evidence presents challenges in its management with uncertain prognosis and monitoring requirements for two aforementioned patients.ConclusionFurther case series and long-term follow up is required for accurate characterisation of phyllodes tumours with heterologous sarcomatous differentiation.     

Actualización en el manejo de sarcomas retroperitoneales y pélvicos; el papel de la cirugía compartimental

Surgery for retroperitoneal sarcomas should be “en bloc” compartmental, which involves resection of unaffected organs. Its upfront use is key, providing a high percentage of resections with negative margins, resulting in a better local control and increased survival in many patients. Preservation of organs should be done in an individualized manner, especially in the pelvic location, and adapted to the histological aggressiveness of the tumor. Preoperative biopsy is able to establish the diagnosis of sarcoma subtype and consequently an adequate perioperative strategy. These patients should be managed by expert surgeons at referral centers with multidisciplinary units and oncology committees. The use of chemotherapy and radiotherapy is not yet well defined, so it is only recommended at referral centers with clinical trials. Currently, this is the only option to offer the best morbidity and mortality rates, as well as possible improvements in the survival of these patients.     

Challenges in the treatment of angiosarcoma: a single institution experience

Background

Angiosarcomas are rare tumors that carry poor prognosis. Because of insidious growth rate, the diagnosis is often difficult and delayed.

Methods

Between 1990 and 2011, 72 (41 female, 31 male) patients were treated at our institution. Pathologic confirmation was obtained and multiple prognostic factors were evaluated for survival.

Results

Forty-four cases were sporadic and 28 cases were secondary. In the sporadic group, 16 (36%) patients had increased sun exposure, while in the secondary group, the majority (n = 23, 82%) of patients had prior exposure to radiation. The latent period between radiation exposure and diagnosis was predictive of survival (P = .037). Presentation was delayed by more than 3 months in 41% of patients. The majority of men developed head and neck angiosarcomas (n = 15, 48.5%), while women developed breast angiosarcomas (n = 21, 51%). Median survival was prolonged in patients treated initially with surgery.

Conclusions

A delay in the diagnosis of angiosarcoma can affect survival. Clinical suspicion and prompt diagnosis are essential for successful multimodal therapy. Initial surgical resection with adjuvant chemotherapy provides survival advantage.     

乳腺癌多药耐药性研究进展

目的：综述乳腺癌多药耐药性研究的最新进展。方法：采用文献回顾的方法，对目前国内、外有关乳腺癌多药耐药性的研究状况加以分析与综述。结果：乳腺癌多药耐药是多基因、多阶段、多步骤、多因素共同作用的结果。如何早期明确化疗药物的敏感性并选择适宜的个体化治疗方案，是避免化疗失败，提高患者生存率和生活质量的一个重要环节。结论：深入研究乳腺癌多药耐药的发生、发展机理，有助于临床预测化疗疗效．分析患者预后，并为最终解决多药耐药这一难题提供有益的帮助。     

Radiotherapy in the treatment of breast cancer: a personal retrospective

Allan Langlands commenced training as a radiation oncologist in 1960 and has continued to treat patients with breast cancer for over 30 years. Moved to Westmead Hospital in Sydney he played a role in the development of radiation oncology in Australia. With an extensive research record (authoring over 200 peer-reviewed papers) this article reflects the changes in breast cancer treatment which have occurred over this period. The incorporation of evidence from the clinical trials in breast cancer management, changes in radiation therapy techniques and incorporation of patient choice in treatment decisions are discussed.     

化疗对乳腺癌患者骨髓抑制的临床分析

目的：评估化疗后乳腺癌患者发生骨髓抑制的风险。方法：对219例乳腺癌患者化疗前后的部分血液学的指标进行比较,并探讨可能与骨髓抑制相关的危险因素。结果：化疗后患者的WBC、N、HB及PLT数值均下降;与骨髓抑制相关的主要因素有：骨髓转移（OR=2.395,P=0.04）、BMI（OR=0.279,P=0.008）、肿瘤分级（OR=2.876,P〈0.001）及化疗周期（OR=4.639,P=0.006）。结论：根据对骨髓抑制相关因素的评估,临床医生可预测乳腺癌患者发生骨髓抑制风险的大小,从而及时地进行预防或纠正。     

What extent of radiation therapy is standard?

This review will address: (1) 'what are the current indications for radiation therapy (RT), following both mastectomy and breast-conserving surgery?' and (2) 'if RT is indicated, what are the appropriate volumes or 'targets' to be treated?' Given the complexity of these questions, this review will focus on selected topics considered of greatest current interest. In addition, this review will primarily focus on results obtained from randomized clinical trials (RCTs). Finally, we acknowledge an American point of view in our discussion.     

Trends in surgical treatment of breast cancer at Mayo Clinic 1980-2004

The study encompassed the time period January 1980 through December 2004. During this time 9485 women underwent mastectomy, 6847 women underwent breast conserving surgery (BCS) and 2477 women underwent breast radiotherapy (RT) for breast cancer. Linear regression modeling was used to quantify the rate of change in the proportion of women undergoing mastectomy during specific time periods. Chi-square tests were used to compare the proportion of women with a breast cancer less than 3 cm in size undergoing mastectomy the year prior to and the year after a specific event.There was a significant decrease in the number and proportion of mastectomies performed, an increase in the number of BCS procedures performed and an increase in the number of women undergoing breast RT around the times of (1) the employment of a young surgeon trained in BCS, (2) publication of the NIH Consensus Statement and (3) establishment of a multidisciplinary Breast Clinic.     

Retroperitoneal and Truncal Sarcomas: Prognosis Depends Upon Type Not Location

Background Prognostication of truncal and retroperitoneal soft tissue sarcomas has traditionally been predicated on tumor location and grade. Objective To compare outcomes for patients with retroperitoneal or truncal sarcomas. Methods Retrospective analysis of a prospective cancer data registry from 1977 to 2004 was performed and outcomes were determined. Results The study group numbered 312 patients (median age 58 years, 54% male, 56% Caucasian, 14% black, 29% Hispanic). The most common tumor types were liposarcoma (35.9%), leiomyosarcoma (30.1%), and malignant fibrous histiocytoma (MFH) (19.5%). Tumor distributions were retroperitoneal (38.9%), pelvic (24.7%), abdominal (18.6%) and thoracic (17.9%). Median overall survival was 74 months. Operative resection was undertaken in 89.4% of cases and multiple surgeries (range 2–5) in 42.2%. Negative resection margins were obtained in 72.7% of patients. Univariate analysis comparing retroperitoneal versus truncal location demonstrated no significant differences in survival. Survival was improved in lower grade tumors (P < 0.02). Liposarcoma and fibrosarcoma were associated with improved survival (P < 0.0001). Multivariate analysis of pre-treatment variables showed increasing age, grade, histopathology (leiomyosarcoma and MFH) and metastasis to be associated with worse outcomes. Multivariate analysis of the treatment variables showed that surgery and negative resection margins were associated with improved survival (P < 0.001). No advantage for chemoradiotherapy could be demonstrated. Conclusions Successful operative resection can confer prolonged disease-free survival and cure for truncal and retroperitoneal sarcomas. Histological subtype, not location, is predictive of long-term survival. Future studies should focus on histological subtype rather than tumor location for truncal and retroperitoneal sarcomas.