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Multimodality Local Therapy for Retroperitoneal Sarcoma
Abstract
Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival.
Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at the University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era.
The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%).
For retroperitoneal sarcoma, local control remains a challenge and combined-modality therapy may be associated with significant acute and late morbidity. Our patterns of failure data suggest that improvements in local control may translate into a survival benefit.
... Surgery is the standard of care for all retroperitoneal sarcomas (RPSs); however, a 25-50% rate of local recurrence after surgery alone remains high [3][4][5][6][7]. Additionally, rates of microscopic and macroscopic positive margins are 12-58% and 20-25%, respectively, with positive margins correlating with poor control [3,[8][9][10][11][12][13][14][15][16][17][18][19]. ...
... Furthermore, STRASS drew attention to patterns of failure, delays to surgery, and the significance of RT-associated toxicity. This trial and other studies suggest that local recurrence accounts for 75% of cancer-related mortality in RPS [5,6] and that margin positivity is associated with worse survival [3,[8][9][10][11][12][13][14][15][16][17][18][19]. ...
Background:
While pre-operative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. However, the risk of toxicity was substantial and the time to surgery was prolonged. A combination of hypofractionation and proton therapy may reduce delays from the initiation of radiation to surgery and limit the dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of the pre-operative ultra-hypofractionated intensity-modulated photon (IMRT) and proton radiotherapy (IMPT).
Methods:
Pre-operative IMRT and IMPT plans were generated on 10 RPS patients. The prescription was 25 Gy radiobiological equivalents (GyEs) (radiobiological effective dose of 1.1) to the clinical target volume and 30 GyEs to the margin at risk, all in five fractions. Comparisons were made using student T-tests.
Results:
The following endpoints were significantly lower with IMPT than with IMRT: mean doses to liver, bone, and all genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose.
Conclusions:
IMPT maintained target coverage while significantly reducing the dose to adjacent OARs and integral dose compared to IMRT. A prospective trial treating RPS with pre-operative ultra-hypofractionated IMPT at our institution is currently being pursued.
... La evidencia actual respecto a radioterapia para sarcomas retroperitoneales es insuficiente, controvertida y sugiere ventajas en control local y supervivencia libre de progresión (especialmente en enfermedad residual), sin embargo, es considerable la radio-toxicidad a órganos y estructuras vitales del retroperitoneo. El control local de TMVNPs se ha asociado a dosis mayores de 60 Gy (3,9,10) . ...
... El seguimiento es más estricto en pacientes con peor diferenciación y la resección paliativa de recurrencias puede ofrecer calidad de vida. La supervivencia a 5 años con sarcomas retroperitoneales y TMVNPs es 50.%-60 % y 20 % 50 %, respectivamente (3)(4)(5)10,15) . ...
Presentamos el caso de un hombre de 50 años, quien padeció un tumor de este
tipo esporádico del retroperitoneo recto-vesical, resección con enfermedad residual macroscópica, quimioterapia (ifosfamida + doxorrubicina) y supervivencia de 10 meses
... Neoadjuvant therapy in the form of external beam radiation, chemotherapy, chemotherapy combined with deep-wave hyperthermia, or combined radiation and chemotherapy is safe for well-selected patients and may be considered after careful review by a multidisciplinary sarcoma tumor board (IVC). [66][67][68][69][70][71][72][73][74][75][76] 20 Intraoperative RT (IORT, with electron beam) has no proven benefit. Although it may be considered for margins considered at risk, the field is often too large and uneven for its practical application (IVE). ...
... A therapeutic radiation dose can be achieved for only the minority of patients after resection, due primarily to gastrointestinal toxicity (IVE). 71,84,85 22 Brachytherapy is of no proven benefit and may be associated with significant short-and long-term complications (IVE). 72,86,87 23. ...
Background:
Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document.
Methods:
The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation.
Results:
Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies.
Conclusions:
Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.
... On the contrary, among patients with good clinicopathological factors, the differences between the CSS and CCSS3 rates were relatively small. For example, among FNCLCC grade III patients, the CSS rate at 8 years was 41 (Table 3). ...
... However, chemotherapy combined with hyperthermia, extracorporeal radiotherapy, or chemoradiotherapy was safe with no fatal complications for carefully selected patients with RPTs. For chemotherapy-sensitive tumors, such as synovial sarcoma and LMS, radiotherapy is recommended for solitary fibrous tumors [38][39][40][41][42][43][44][45]. ...
Background
The purpose of this study was to assess conditional survival (CS) after resection of primary retroperitoneal tumors (RPTs).
Methods
The data of 1594 patients with primary RPTs who underwent surgery between 2004 and 2016 were retrieved from the Surveillance Epidemiology and End Results (SEER) database. Multivariate Cox analysis was used to identify prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS). CS was used to calculate the probability of survival for an additional 3 years after the patient had survived x years, according to the formulas: COS3 = OS (x + 3) /OS (x) and CCSS3 = CSS (x + 3)/CSS (x).
Results
The 1-, 3-, and 5-year OS rates of all patients were 89.8, 71.8, and 60.8%, while the 1-, 3-, and 5-year CSS rates were 91.9, 77.1, and 67.8%, respectively. Age, sex, FNCLCC grade, size, multifocality, histology, and chemotherapy were independent prognostic factors for OS and CSS. Among patients who survived for 1, 3, and 5 years, the COS3 rates were 72.9, 77.9, and 79.3%, and the CCSS3 rates were 78.1, 82.7, and 85.8%, respectively. Patients with poor clinicopathological characteristics achieved greater improvements in COS3 and CCSS3 rates, and the survival gaps between OS and COS3, as well as CSS and CCSS3 were more obvious.
Conclusion
Postoperative CS of RPTs was dynamic and increased over time. CS increased more significantly in patients with poor clinicopathological characteristics.
... The majority of patients with PRPLS are diagnosed at an advanced disease stage, therefore PRPLS tumors often grow to a large size and have invaded adjacent organs upon diagnosis (22). The benefits of using adjuvant chemotherapy and radiation therapy to treat PRPLS remains controversial (23,24). A number of studies have suggested that chemotherapy may worsen patient prognosis (25,26). ...
... A number of studies have suggested that chemotherapy may worsen patient prognosis (25,26). Other studies have reported that chemotherapy has limited effectiveness for PRPLS, but is beneficial for liposarcomas originating from the lower or upper extremities (23,27). Radiation can result in clinical complications, including nerve lesions, hydronephrosis, ureteral fistula and ileus (28). ...
Primary retroperitoneal liposarcoma (PRPLS) is the most common soft tissue malignancy of the retroperitoneum. To determine the pathological features and the curative effects of surgery in patients with PRPLS, and to elucidate key prognostic factors, the present study retrospectively analyzed the clinical cases of 65 patients with PRPLS. Immunohistochemical analysis demonstrated that vimentin and Ki-67 are better indicators for PRPLS immunohistochemical diagnosis compared with S-100 protein. S-100 protein was predominantly expressed in well-differentiated PRPLS. Positive expression of vimentin and Ki-67 were observed in almost all PRPLS samples, and Ki-67 exhibited a higher expression level in high-grade PRPLS. The level of Ki-67 expression was negatively correlated with disease-specific survival (DSS). Survival analysis revealed that the pathological subtype and histological grade were associated with DSS and local recurrence in the patients, whereas the tumor burden was associated with DSS but not local recurrence. In addition, complete tumor resection and contiguous organ resection were able to improve DSS. Microscopically positive margins did not affect DSS, whereas gross margins did. Multivariate analysis revealed that pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, and that histological grade was an independent factor for local recurrence. Patient sex and age at presentation were not independent factors associated with prognosis or local recurrence. Correlation analysis demonstrated that postoperative local recurrence significantly affected DSS, and local recurrence was the most common cause of mortality among patients. Histological grade was strongly associated with the invasion of adjacent organs but not with tumor burden. Furthermore, the tumor burden was not associated with recurrence or tumor invasion of adjacent organs. Ki-67 expression was associated with prognosis. Pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, while histological grade was an independent factor which affected tumor recurrence.
... Menos del 5% de las lesiones afectan tejido linfático y en algunos subtipos no están indicadas las disecciones linfáticas de rutina. Algunas contraindicaciones para la resección son: afección extensa del mesenterio, infiltración neurovascular, sarcomatosis peritoneal y enfermedad metastática (7,8). La resección multiorgánica (riñón, glándula suprarrenal, colon, páncreas y bazo) se practica en gran número de casos (8). ...
... Algunas contraindicaciones para la resección son: afección extensa del mesenterio, infiltración neurovascular, sarcomatosis peritoneal y enfermedad metastática (7,8). La resección multiorgánica (riñón, glándula suprarrenal, colon, páncreas y bazo) se practica en gran número de casos (8). ...
Los sarcomas de tejido blando representan menos del 1% de las neoplasias en humanos. Un tercio de los tumores malignos que aparecen en el retroperitoneo son sarcomas y los liposarcomas son los sarcomas retroperitoneales más comunes y se conoce que crecen hasta tamaños gigantes, progresan lentamente y producen pocos y tardíos síntomas. Se reporta el caso de una mujer de 40 años de edad con un liposarcoma retroperitoneal gigante. Se realizó la laparotomía y se encontró un tumor multilobulado de 20 centímetros de diámetros que se originaba en el retroperitoneo. Las características histológicas fueron sugestivas de liposarcoma pleomórfico que pesaba 8,5 Kilogramos
... • The University of Florida recently updated their experience with multimodality therapy in RPS [36]. In 58 patients, the 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. ...
... There has been some suggestion of a dose-response relationship in RPS. A National Cancer Institute, prospective, randomized trial in 35 patients, compared IORT (20 Gy) and low-dose PORT (35)(36)(37)(38)(39)(40) with conventional PORT (50-55 Gy) [24]. Reduced local failures and lower GI toxicities were noted in the IORT arm; however, peripheral neuropathy was more common in the IORT arm. ...
Opinion statement:
Retroperitoneal sarcomas form a group of rare malignancies that require expertise in every aspect of management. Patients benefit from referral to cancer centers that can provide comprehensive, multidisciplinary, oncologic management. The role of radiation in retroperitoneal sarcoma management is, appropriately, the subject of considerable controversy due to the absence of high-level evidence proving its efficacy. Nonetheless, the preponderance of available data suggests that radiation therapy likely improves local control and, in some settings, may favorably impact resectability and survival. These outcome observations coupled with the lower doses (45-54 Gy) and normal tissue displacement characteristic of preoperative radiation therapy leads us to favor preoperative radiotherapy followed by oncologic resection for most retroperitoneal sarcomas. This strategy appears to provide the highest chance of safe and successful delivery of multimodal therapy, which can otherwise be hindered by postoperative complications as a result of technically challenging surgery and normal tissue radiation dose tolerances. Dose-escalation and selective integrative boosts to "at-risk" margins are attractive strategies that merit, and arguably require, further clinical evaluation. We believe that postoperative radiotherapy should be reserved for very high-risk cases and should be treated to a dose of ≥60 Gy respecting normal tissue dose tolerances. An additional approach that we consider in the postoperative setting is close surveillance with consideration of preoperative radiotherapy at recurrence before repeat surgical resection. Highly conformal radiotherapy techniques, such as IMRT with image guidance, should be employed to minimize dose to normal tissues and thereby allow delivery of efficacious radiation doses. If feasible, referral to a treatment facility with proton beam therapy should be discussed with the patient, especially if normal tissue dose constraints cannot be met using IMRT/IGRT. Participation in prospective studies should be highly encouraged.
... To obtain clear surgical margins and considering the highly aggressive nature of retroperitoneal liposarcomas and their propensity for local recurrence and distant metastasis, complementary adjuvant/neoadjuvant therapy may be required [16]. However, adjuvant therapy including either chemotherapy and/or radiotherapy is of little study-proven value and just benefit a minority of patients [17,18]. The role of chemotherapy is not as well defined as is the role of radiation therapy. ...
Background and objectives
Retroperitoneal liposarcoma (RPLS) are common soft tissue sarcomas of adulthood. The aim of this study is to show resectability of even giant liposarcomas and to identify factors associated with recurrence and survival in primary retroperitoneal liposarcomas.
Methods
We retrospectively reviewed the records of patients with retroperitoneal liposarcoma. Seventy-seven patients met inclusion criteria. Out of these 10 patients with primary giant, dedifferentiated retroperitoneal liposarcomas were operated with en bloc compartment resection with intention of radical resection. Treatment consisted of neoadjuvant radiochemotherapy and surgical resection or surgical resection.
Results
In 6 patients, neoadjuvant radiochemotherapy was performed; 3 patients were treated with surgical resection alone and 1 patient received adjuvant chemotherapy. The median diameter of tumor size was 360 mm (300 to 440 mm). Operative outcome showed complete resection in all 10 patients. Local tumor free survival was in median 19 month. Tumor recurrence was seen in 3 of 4 patients (75%) without neoadjuvant radiochemotherapy, and in 2 of 6 patients (33%) after neoadjuvant radiochemotherapy in 2 years follow-up.
Conclusion
Even in case of giant retroperitoneal liposarcoma, complete resection is possible and remains the principal treatment. The rate of recurrence was improved in patients with neoadjuvant radiochemotherapy.
... However, achieving adequate dose and target coverage in the retroperitoneum is challenging due to the close proximity of surrounding critical structures such as small bowel, kidneys, liver and spinal cord. RT doses are often limited to 45-50 Gy using older techniques and grade 3 or greater toxicity can approach 40-50% even with these suboptimal doses [8,9]. Unfortunately, local recurrence rates remain high even if doses of 50-55 Gy can be safely administered with conventional RT [7,9]. ...
Background:
Peri-operative radiation of retroperitoneal sarcomas (RPS) is an important component of multidisciplinary treatment. All retrospective series thus far included patients treated with older radiation therapy (RT) techniques including 2D and 3DRT. Intensity modulated radiation therapy (IMRT) allows for selective dose escalation while sparing adjacent organs. We therefore report the first series of patients with RPS treated solely with IMRT, surgery and chemotherapy. We hypothesized that IMRT would permit safe dose escalation and superior rates of local control (LC) in this high-risk patient population.
Methods:
Thirty patients with RPS treated with curative intent between 2006 and 2015 were included in this retrospective study. RT was administered either pre- or post-operatively and IMRT was used in all patients. Statistical comparisons, LC, distant metastasis (DM), and overall survival (OS) were calculated by Kaplan-Meier analysis and univariate Cox regression.
Results:
Median follow-up time after completion of RT was 36 months (range 1.4-112). Median tumor size was 14 cm (range 3.6 - 28 cm). The most prevalent histologies were liposarcoma in 10 (33%) patients and leiomyosarcoma in 10 (33%) with 21 patients (70%) having high-grade disease. Twenty-eight (93%) patients had surgical resection with 47% having positive margins. Chemotherapy was administered in 9 (30%) patients. RT was delivered pre-operatively in 11 (37%) patients, and post-operatively in 19 (63%) with 60% of patients receiving a simultaneous integrated boost. Pre-operative median RT dose to the high-risk area was 55 Gy (range, 43-66 Gy) while median post-operative dose was 60.4 Gy (range, 45-66.6 Gy). There was one acute grade 3 and one late grade 3 toxicity and no grade 4 or 5 toxicities. Three year actuarial LC, freedom from DM, and OS rates were 84%, 64%, and 68% respectively. Positive surgical margins were associated with a higher risk of local recurrence (p = 0.02) and decreased OS (p = 0.04). Pre-operative RT was associated with improved LC (p = 0.1) with a 5-year actuarial LC of 100%. Administration of chemotherapy, timing of RT, histology or grade was not predictive of OS.
Conclusions:
Patients with RPS treated with peri-operative IMRT at our institution had excellent local control and low incidences of toxicity.
... 34 However, adjuvant therapy including chemotherapy and radiotherapy are of few study-proven value and just benefit a minority of patients. [35][36][37] Furthermore, after 2 small randomized trials, Beane 38 Large tumor size should not be regarded as a contraindication to surgical resection. Even gigantic, complete surgical cure can also be achieved in giant RPLS with a thorough program. ...
Retroperitoneal liposarcoma (RPLS) is a rare tumor, especailly those over 20 kg that are called “giant liposarcoma”, whose characteristics and treatments remain relatively unknown. Herein, we report a giant RPLS measuring 65 × 45 × 30 cm in diameter and 31 kg in weight, which we successfully performed complete excision through interdisciplinary cooperation. The patient had an uneventful postoperative course and was discharged without complications. Afterwards he underwent radiotherapy and had no evidence of tumor recurrence or symptoms of metastasis at 3-month CT scan and 8-month follow-up. We also firstly review the thirteen cases reported in literature published in PubMed regarding giant RPLS. Giant RPLS commonly occurs in adults aged 40–60 years and presents atypical clinical manifestations. CT scan is the most useful examination and preoperative biopsy is controversial. Complete surgical resection still remains the principal treatment. Giant RPLS can also be removed, even reach to R0 excision, by a multidisciplinary team in a specialized center after meticulous planning even though its gigantic tumor size. Local radiotherapy following surgery may improve the rate of recurrence. Besides, closely follow-up and routine examinations are required.
... Similarly, perioperative chemotherapy is far from being standard treatment and is not currently supported by established consensus guidelines [23]. However, where histology is chemosensitive and the risk of systemic failure is high or a locally advanced tumour potentially rendered resectable, then perioperative chemotherapy can be considered [48,50,53,54]. Examples include leiomyosarcoma of the inferior vena cava, where the risk of pulmonary metastases is high, or a locally advanced synovial sarcoma [55e58]. ...
The management of soft tissue sarcoma is challenging and varied. Centralisation of management in high volume specialist centres has revolutionised outcomes. Surgery remains the mainstay of treatment and is currently the only potentially curative therapy. Retroperitoneal soft tissue sarcoma presents a particular challenge to the surgical oncologist and the concept of extended resection to include surrounding expendable organs taken en bloc with the tumour has now largely been adopted. The use of neoadjuvant and adjuvant therapies for retroperitoneal soft tissue sarcoma is still to be established, although they are employed on a case-specific basis. Guidance on the management of retroperitoneal recurrences and distant metastatic disease is now recognised. The approach to soft tissue sarcoma of the head and neck, trunk and abdominal wall remains largely extrapolated from experience of the management of extremity soft tissue sarcoma. Secondary angiosarcoma of the breast is becoming increasingly more common and presents a particular therapeutic challenge. Continued international collaboration is essential to ensure evolution of the optimal management of this rare group of cancers.
... Incidences of postoperative complications are also numerically less than that found in existing photon data (80). Additionally, publications of retroperitoneal PBT have produced a total of two toxicities amongst the 48 total patients in both reports, which is in stark contrast to an estimated 39% grade ≥3 toxicity rate seen in photon-based treatment as presented at ASTRO (81). ...
Background:
Proton beam radiotherapy (PBT) is frequently shown to be dosimetrically superior to photon radiotherapy (RT), though supporting data for clinical benefit are severely limited. Because of the potential for toxicity reduction in gastrointestinal (GI) malignancies, we systematically reviewed the literature on clinical outcomes (survival/toxicity) of PBT.
Methods:
A systematic search of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology was conducted for publications from 2000-2015. Thirty-eight original investigations were analyzed.
Results:
Although results of PBT are not directly comparable to historical data, outcomes roughly mirror previous data, generally with reduced toxicities for PBT in some neoplasms. For esophageal cancer, PBT is associated with reduced toxicities, postoperative complications, and hospital stay as compared to photon radiation, while achieving comparable local control (LC) and overall survival (OS). In pancreatic cancer, numerical survival for resected/unresected cases is also similar to existing photon data, whereas grade ≥3 nausea/emesis and post-operative complications are numerically lower than those reported with photon RT. The strongest data in support of PBT for HCC comes from phase II trials demonstrating very low toxicities, and a phase III trial of PBT versus transarterial chemoembolization demonstrating trends towards improved LC and progression-free survival (PFS) with PBT, along with fewer post-treatment hospitalizations. Survival and toxicity data for cholangiocarcinoma, liver metastases, and retroperitoneal sarcoma are also roughly equivalent to historical photon controls. There are two small reports for gastric cancer and three for anorectal cancer; these are not addressed further.
Conclusions:
Limited quality (and quantity) of data hamper direct comparisons and conclusions. However, the available data, despite the inherent caveats and limitations, suggest that PBT offers the potential to achieve significant reduction in treatment-related toxicities without compromising survival or LC for multiple GI malignancies. Several randomized comparative trials are underway that will provide more definitive answers.
... Historically, the 5-year survival rate and local control rate have varied widely depending on the series, ranging between 40-80% and 50-70%, respectively [2]. R0 margins are an acknowledged positive prognostic factor, associated with improved overall survival and local control [31][32][33]. Recently, surgeons in some high volume centers have routinely performed compartmental resection. ...
Background:
Retroperitoneal sarcomas are connective tissue tumors arising in the retroperitoneum. Surgical resection is the mainstay of treatment. Debate has arisen over extent of resection, changes in histological classification/grading, and interest in incorporating radiotherapy. Therefore, we reviewed our institution's experience to evaluate prognostic factors.
Methods:
Retrospective chart review of all primary RPS patients at Johns Hopkins Hospital from 1994 to 2010. Histologic diagnosis and grading were re-evaluated with current criteria. Prognostic factors for survival, and recurrence were assessed.
Results:
One hundred thirty-one primary RPS patients met inclusion criteria. Median survival for patients who undergo en-bloc resection to negative margins (R0/R1) is 81.7 months. Surgical margins and grade were the most important factors for survival along with age, gender, presence of metastases and resection of ≥5 organs. Five-year survival for R0/R1 resection was 60%, similar to compartmental resection. Radiotherapy significantly decreased local recurrence (P = 0.026) on multivariate analysis. Grade in leiomyosarcomas and dedifferentiation in liposarcomas dictated patterns of local versus distal recurrence.
Conclusions:
En bloc surgical resection to R0/R1 margins remains the cornerstone of therapy and provides comparable outcomes to compartmental resections. Grade remains important for prognosis, and histology dictates recurrence patterns. Radiotherapy appears promising for local control and warrants further investigation. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
... Frozen section analysis may be of assistance in particular circumstances, for instance, in cases of vascular LMS or to assess neural margins of excision (VA). [33][34][35][36][37][38][39][40][41][42] This is particularly relevant in the case of technically unresectable/borderline resectable RPS that could potentially be rendered resectable by downsizing, and also for chemo-sensitive histologies such as synovial sarcoma, 43 LMS of the inferior vena cava, and the like (VC). The sensitivity of solitary fibrous tumor to X-ray therapy (XRT) also should be considered (IVB). ...
Background
Retroperitoneal soft tissue sarcomas (RPS) are rare tumors that include several well-defined histologic subtypes. Although surgery is the mainstay of curative therapy, no universally accepted recommendations concerning the best management have been developed to date. Optimization of the initial approach is critical for maximizing patient outcomes. Methods
An RPS Trans-Atlantic Working Group was established in 2013. The primary aim was to evaluate the current evidence critically and to develop a consensus document on the approach to this difficult disease. The outcome applies to primary RPS that is nonvisceral in origin. The evaluation included sarcomas of major veins (inferior vena cava, renal vein, ovarian/testicular vein), undifferentiated pleomorphic sarcoma of the psoas, and ureteric leiomyosarcoma (LMS). It excluded desmoid, lipoma and angiomyolipoma, gastrointestinal stromal tumors, visceral sarcomas such as those arising from the gut or its mesentery, uterine LMS, prostatic sarcoma, paratesticular/spermatic cord sarcoma, Ewing’s sarcoma, alveolar/embryonal rhabdomyosarcoma, primitive peripheral neuro-ectodermal tumor, sarcoma arising from teratoma, carcinosarcoma, sarcomatoid carcinoma, clear cell sarcoma, radiation-induced sarcoma, paraganglioma, and malignant pheochromocytoma. ResultsManagement of RPS was evaluated from diagnosis to follow-up, and a level of evidence was attributed to each statement. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the statements included in this article. Conclusions
International collaboration is critical for adding to the current knowledge. A prospective registry will be set up.
... 3 The large potential space of the retroperitoneum and capacity for the abdominal cavity to expand allow for progressive growth of retroperitoneal sarcomas, which may remain undetected until late in the disease history. 4 If symptomatic, patients often suffer with abdominal distension, altered bowel motions and abdominal discomfort, 5 and occasionally weight loss and anaemia. 3 Often, the diagnosis is made incidentally following investigation for another indication. ...
Retroperitoneal sarcomas are a rare disease. The overall 5-year survival rate for these lesions remains low, and surgical management offers the only option for effective treatment and potential for cure. Radiotherapy is increasingly being employed in addition to standard surgical treatment. Improvements in cross-sectional imaging have also facilitated better characterisation of lesions, preoperative planning and long-term follow-up. This article reviews the current literature and documents the various types of retroperitoneal sarcomas with a particular approach to their imaging features. We also highlight the pathology, diagnostic methods and most current management of these tumours.
... Despite aggressive treatments, prognosis remains poor with 5y-OS typically between 35 and 50% (Table IV) (10). Our results with an actuarial 5y OS of 51% are in accordance with current literature. ...
The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <15 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p 5 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.
... Although some studies have reported that radiation therapy is beneficial for RPS, its effect on survival is still under debate. Morbidities due to toxicity on adjacent radiosensitive central organs remain an important obstacle [2,10,11,22-28]. ...
This is a report of the surgical treatment and prognosis of retroperitoneal liposarcoma (RPLS) in Koreans.
Nineteen patients treated for RPLS between July 1, 1984, and March 31, 2009, were included. Patient demographics, histopathologic subtypes, survival rate, disease recurrence rate and interval, and adjuvant therapy were reviewed and analyzed.
Of the 19 patients diagnosed with RPLS, 26.3% presented with well-differentiated RPLS, 10.5% with dedifferentiated RPLS, 15.8% with myxoid/round cell type, and 47.4% with mixed-type liposarcoma. The mean follow-up period was 66.8 months (range, 6 to 165 months). Primary RPLS was treated in 17 patients. Nine patients (52.9%) had recurrent disease, and recurrence developed at a mean of 47.7 months after primary or repeated surgical treatment. The overall survival rate was 84.2% during a mean follow-up of 66.8 months. The 3- and 5-year survival rates were 86.9%, and the 10-year survival rate was 69.5%. The recurrence interval was significantly shorter in recurrent RPLS cases (p=0.023). The mean growth rate of locally recurrent tumors was 0.34 cm per month.
The survival rates reported here were higher than in previous studies. Locally recurrent tumors presented with a low growth rate, which may have contributed to the relatively high survival rate. A high prevalence of mixed-type RPLS was also noted, and its cause and prognosis require further research.
Background
Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) after surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined because the natural history of RP-LPS after treatment is poorly understood. This study evaluated the long-term risk of recurrence and disease-specific survival (DSS) for a cohort of patients with at least 10 years of progression-free survival (10yr-PFS) from their primary resection.Methods
The prospective University of California, Los Angeles (UCLA) Sarcoma Database identified RP-LPS patients with 10yr-PFS after initial resection. The patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. The time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS.ResultsFrom 1972 to 2010, 76 patients with RP-LPS had at least 10 years of follow-up evaluation. Of these 76 patients, 39 (51%) demonstrated 10yr-PFS. The median follow-up period was 15 years (range 10–33 years). Among the 10yr-PFS patients, 49% (19/39) experienced a recurrence at least 10 years after surgery. Of those who experienced recurrence, 42% (8/19) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or perioperative treatment with radiation or chemotherapy.Conclusion
Patients who have primary RP-LPS treated with surgical resection ± multimodality therapy face a long-term risk of recurrence and disease-specific death unacknowledged by current surveillance imaging guidelines. Among the patients with 10yr-PFS, 49% experienced a recurrence, and 42% of those died of disease. These findings suggest a need for lifelong surveillance imaging for patients with RP-LPS.
Purpose:
The role of radiation therapy (RT) in resectable retroperitoneal sarcoma (RPS) remains controversial; however, preoperative RT may play an important role in borderline-resectable (at risk of R2 resection) disease. We evaluated the outcome of such patients treated with preoperative dose-painting IMRT followed by planned resection.
Methods:
Between January 2001 and December 2017, 30 patients with borderline-resectable primary nonmetastatic RPS (after multidisciplinary review) received preoperative dose-painting IMRT in this retrospective cohort study.
Results:
Median follow-up for all patients was 32 months. Median dose to the whole tumor/high-risk margin was 50.4 Gy/60.2 Gy. Sixteen patients were female, 24 were >50 years. Median tumor size was 9.2 cm. After RT, 6 did not have surgery. Of the 24 who were explored, 20 underwent complete gross resection. During RT, 7 of 30 patients developed acute grade 2+ toxicities: 5 fatigue, 1 nausea and vomiting, and 1 cystitis. RT was completed in 29 of 30 patients. Postoperatively, 12 of 20 patients developed grade 2+ complications: 2 gastropathy, 5 intraabdominal collections requiring drainage, 1 retroperitoneal bleed, and 3 delayed wound healing. Late grade 2+ toxicity was observed in 3 of 20 patients: 1 lymphedema with recurrent cellulitis, 1 chronic diarrhea, 1 gastrointestinal bleeding from anastomosis requiring transfusions, and 2 renal insufficiency. In those who underwent complete gross resection (n = 20, median follow-up 47 months), the 5-year local control was 57%, and overall survival was 46%.
Discussion:
Preoperative dose-painting IMRT given to borderline-resectable RPS rendered 67% of patients resectable, provided a 5-year local control rate of 57%, which is similar to those with resectable disease, and had an acceptable morbidity profile.
Background
Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy.
Patients and methods
We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy.
Results
With a median follow-up of 24 months (2–114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2.
Conclusions
Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.
Retroperitoneale Sarkome gehören zur Klasse der Weichgewebssarkome und sind seltene maligne Tumore. Aufgrund ihrer Lage kommt es oft erst zu einer späten Diagnosestellung. Aktuell bestehen keine einheitlichen Daten aus Krebsregistern oder verbindliche Leitlinien bezüglich der primären Diagnostik und Behandlung dieser seltenen Tumorentität. Um einen Überblick über die aktuell bestehenden Behandlungsoptionen zu erhalten, erfolgte die Erstellung und Durchführung einer Online-Umfrage. Die vorliegende Umfrage wurde mithilfe einer Online-Plattform durchgeführt. Hierbei wurden alle chirurgischen Abteilungen und Kliniken deutscher Krankenhäuser angeschrieben. Der dabei auszufüllende Fragebogen konnte in vier Abschnitte unterteilt werden und enthielt Fragen zur üblichen Diagnostik, Behandlungsstrategien, multimodaltherapeutische Ansätze sowie einen allgemeinen Fragebogenteil. Insgesamt konnte ein Rücklauf von 20 Prozent verzeichnet werden. Die niedrige Inzidenz spiegelte sich in der Anzahl der behandelten Patienten wider, diese lag in den meisten Kliniken unter zehn Patienten pro Jahr. Die meisten Patienten erhalten im Rahmen der Diagnostik eine Schnittbildgebung des Abdomens. Zur Ausschlussdiagnostik einer Lungenmetastase kommt es in fast allen Kliniken zur Durchführung einer Computertomografie. Es zeigte sich, dass nur in gut der Hälfte eine präoperative Biopsieentnahme erfolgt. Als Operationsverfahren wird in den meisten Fällen eine radikale Kompartmentresektion durchgeführt. Erstaunlicherweise entscheiden sich 40 Prozent im Rahmen der Operation zu einer additiven Lymphadenektomie. Eine zusätzliche Radio-/ Chemotherapie erfolgt in den meisten Kliniken nicht regelhaft. Bei differenzierter Betrachtung der Ergebnisse zeigten sich teils deutliche Unterschiede der Vorgehensweisen abhängig von der jährlich behandelten Patientenzahl. Insgesamt unterstreichen die Ergebnisse der Umfrage, dass es aufgrund geringer Fallzahlen und fehlender S3-Leitlinien zu uneinheitlichen Vorgehensweisen in der Behandlung retroperitonealer Sarkome kommt. Zum Teil scheint es, dass Grundsätze der Karzinomchirurgie und Behandlung unkritisch auf die Sarkomchirurgie übertragen werden. Umso wichtiger scheint es, dass betroffene Patienten in Zentren behandelt werden, die eine vergleichsweise hohe Behandlungsrate vorweisen können. Dies wird auch durch aktuelle Daten aus Tumorzentren in Frankreich belegt. Die Vorstellung im Sarkomboard und damit die primäre Behandlung mit notwendiger Expertise verbessert das Überleben. In Deutschland wird aktuell durch die Krebsgesellschafft eine Struktur zertifizierter Sarkomzentren aufgebaut und eine aktuelle S3-Leitlinie entwickelt. Als Qualitätsindikatoren wurden hier u.a. prätherapeutische Biopsien und die Vorstellung in einem Sarkomboard definiert. Von großem Interesse wäre daher nachzuprüfen, ob in wenigen Jahren eine ähnliche Umfrage zu entsprechenden Ergebnissen führt. Die Motivation der Chirurgen zur Verbesserung der Behandlung zeigt sich nicht zuletzt durch die Teilnahme an dieser Umfrage und an der hohen Anzahl von Teilnehmern, die sich die Etablierung eines RPS-Registers und eines Workshops zu Diagnostik und Therapie retroperitonealer Sarkome wünschen.
Sarkome sind seltene Tumoren, die weniger als 1 % der neudiagnostizierten Malignome des Erwachsenen jährlich ausmachen. Weichteilsarkome können in jedem Teil des Körpers vorkommen; in abnehmender Inzidenz werden sie wie folgt diagnostiziert: Extremitäten (59 %), Rumpf (19 %), Retroperitoneum (13 %), Kopf und Hals (9 %). Gastrointestinale Stromatumore (GIST) sind auch seltene Neoplasien, die sich von den mesenchymatösen Zellen des gastrointestinalen Traktes entwickeln. Die meisten GIST werden im Magen diagnostiziert. Die Rezidivrate beider Tumorgruppen (Sarkome > GIST) ist relativ hoch einzuschätzen. Die Autoren dieses Kapitels stellen sowohl die epidemiologischen, klinischen und diagnostischen Grundlagen als auch die Prinzipien der operativen Therapie dieser Tumoren dar. Die Strategien der nichtoperativen Therapie dieser Entitäten werden diskutiert.
Background and objectives:
The multi-modal treatment of retroperitoneal sarcoma has seen increased use of neoadjuvant radiation. However, its effect on local recurrence and survival remain controversial. We aimed to synthesize and evaluate the literature.
Methods:
The review was conducted according the recommendation of the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) group with pre-specified inclusion and exclusion criteria.
Results:
Of 8,701 citations collected, 15 articles reported on 464 patients. The median age was 56 years (45-64). The predominant histological subtypes were liposarcoma (51.54%) and leiomyosarcoma (23.26%). Tumor differentiation composed of 37.1% well-, 12.8% moderate-, 46.0% poorly-, and 4.1% undifferentiated. Most studies featured external beam radiation therapy (EBRT) treatment regimen with some who included patients treated with IMRT instead. Median follow-up averaged 41.4 months (19-106 months). Median 5-year OS, PFS, and LRR rates were 58%, 71.5%, and 25%. Using the NCI CTCAE, toxicities from Grade 1 (Mild) through Grade 5 (death) were experienced by 18.8%, 10.2%, 16.3%, 0.7%, and 1.6% of patients.
Conclusions:
NART is a safe to use for RPS, but its effect toward survival and local control remains unclear. Without randomized control trials, common reporting criteria for pro- and retrospective studies are needed to allow comparison between studies. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
Objectives:
Controversy persists on the use of adjuvant radiotherapy (RT) in patients with retroperitoneal sarcoma (RPS). High-grade disease is known to be associated with decreased local control and overall survival (OS). Because RT has proven beneficial for local control and OS in patients with high-grade extremity soft tissue sarcoma, we evaluated the efficacy of adjuvant RT in high-grade RPS.
Methods:
The Surveillance, Epidemiology, and End Results database was used to identify patients with pathology-confirmed RPS from 1973 to 2010. Clinical characteristics and outcomes were analyzed.
Results:
Of 480 total patients, 144 (30.0%) received postoperative radiation. Patients who received adjuvant RT had improved median OS (36 mo) compared with those who did not (27 mo, hazard ratio [HR]=0.79, P=0.023). On multivariate analysis the use of adjuvant RT (HR=0.80; 95% confidence interval [CI], 0.65-0.98; P=0.029), male sex (HR=1.32; 95% CI, 1.10-1.59; P=0.003), age above 65 years (HR=1.38; 95% CI, 1.15-1.67; P=0.001), and increasing the Surveillance, Epidemiology, and End Results historical stage (HR=1.46; 95% CI, 1.21-1.76; P<0.001) were all prognostic factors for OS.
Conclusions:
In a large retrospective analysis, postoperative RT improved OS in high-grade RPS patients. As such, adjuvant RT should be strongly considered in all patients with high-grade RPS. The optimal timing of RT relative to surgery requires further study.
The malignant peripheral nerve sheath tumor (neurofibrosarcoma, malignant Schwannoma) is rare, the 65% is associated with neurofibromatosis type 1 (Von- Recklinghausen disease), 20% - 50% of 5 years survival and retroperitoneal location represents a surgical challenge and controversies regarding for the use radiotherapy. We report the case of 50 years old man, who suffered sporadic type of this tumor of recto bladder retro peritoneum, resection with gross residual disease, chemotherapy (ifosfamide + doxorubicin) and survival of 10 months. The poor response to conventional treatment is encouraging clinical and translational research on new alternatives and multimodality.
The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS).
We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n=42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy).
Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P<.001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P<.001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P<.001) and RT dose of ≥60 Gy (P<.001).
Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended.
Copyright © 2015 Elsevier Inc. All rights reserved.
Background:
Radiation delivered as brachytherapy (BRT) via catheters placed during extremity soft tissue sarcoma (STS) resection results in acceptable local control rates; however, there are limitations in deep cavities. (125)I seeds embedded in mesh provide a flexible BRT platform that may be contoured to irregular deep cavities surfaces, but the risks and benefits are unknown.
Methods:
Patients with thoracic, abdominal, pelvic, retroperitoneal, and deep truncal STS undergoing resection and implantation of permanent (125)I mesh BRT at our institution were reviewed. Local recurrence rates within the tumor bed covered by mesh (in field) and postoperative complications were analyzed.
Results:
Between 2000 and 2010, a total of 46 patients were treated for primary (n = 8, 17 %) or recurrent (n = 38, 83 %) deep cavity STS (median follow-up 34.8 months); 74 % received external-beam radiotherapy for this or a prior presentation. In-field recurrences were observed in 9 patients (19.5 %). Crude cumulative incidences of in-field, regional, and distant recurrences at 5 years were 26.3, 54.2, and 54.1 %, respectively. 5-year overall survival rate was 47.2 %; median survival was 44.0 months. Twenty-two patients (48 %) experienced complications, half of whom (24 %) developed grade III/IV complications requiring percutaneous intervention (n = 6) or reoperation (n = 5) at a median of 35.5 days. There were no postoperative deaths.
Conclusions:
To our knowledge, this is the first study to report safety and efficacy for permanent (125)I mesh BRT implantation after resection of deep cavity STS. Local in-field recurrence rates were relatively low in this high-risk population. However, 24 % developed complications requiring intervention. (125)I mesh BRT appears effective, but it should be used with caution.
Purpose:
To determine the positional and volumetric changes of retroperitoneal sarcomas (RPS) during pre-operative external beam radiotherapy (PreRT).
Material and methods:
After excluding 2 patients who received chemotherapy prior to PreRT and 15 RPS that were larger than the field-of-view of cone-beam CT (CBCT), the positional and volumetric changes of RPS throughout PreRT were characterized in 19 patients treated with IMRT using CBCT image guidance. Analysis was performed on 118 CBCT images representing one image per week of those acquired daily during treatment. Intra-fraction breathing motions of the gross tumor volume (GTV) and kidneys were measured in 22 RPS patients simulated using 4D-CT. Fifteen other patients were excluded whose tumors were incompletely imaged on CBCT or who received pre-RT chemotherapy.
Results:
A GTV volumetric increase (mean: 6.6%, p=0.035) during the first 2 weeks (CBCT1 vs. CBCT2) of treatment was followed by GTV volumetric decrease (mean: 4%, p=0.009) by completion of radiotherapy (CBCT1 vs. CBCT6). Internal margins of 8.6, 15 and 15 mm in the lateral, anterior/posterior and superior/inferior directions would be required to account for inter-fraction displacements. The extent of GTV respiratory motion was significantly (p<0.0001) correlated with more superiorly positioned tumors.
Conclusion:
Inter-fraction CBCT provides important volumetric and positional information of RPS which may improve PreRT quality and prompt re-planning. Planning target volume may be reduced using online soft-tissue matching to account for interfractional displacements of GTVs. Important breathing motion occurred in superiorly placed RPS supporting the utility of 4D-CT planning.
Purpose:
To examine the value of surgical resection combined with preoperative external beam radiation therapy and intraoperative radiation therapy (Surg-RT) for retroperitoneal sarcoma (RPS).
Methods:
Review of 63 consecutive patients with RPS from 1996 to 2011.
Results:
Thirty-seven patients (59%) underwent Surg-RT and 26 (41%) had surgery alone. 51% of tumors were high grade and 36% of patients had locally recurrent disease. Final margin status was: R0 73%, R1 16%, R2 6%, and unknown 5%. Of those with R0 resections, 67% received Surg-RT. Median follow-up was 45 months. The 5-year local control rate was 89% for Surg-RT patients and 46% for surgery alone patients (P = 0.03). On multivariate analysis, Surg-RT was the only variable associated with a lower risk of LR (HR 0.19; CI 0.05-0.69, P = 0.003). The actuarial 5-year OS was 60% for patients receiving either Surg-RT or surgery alone.
Conclusions:
The combination of pre-operative radiation, surgical resection, and intraoperative radiation produces excellent local disease control for RPS. Combination therapy was associated with improved local control but not with overall survival.
Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS.
From June 1996 to October 2000, eligible patients with resectable RPS were entered onto a phase II trial of preoperative XRT (45-50Gray) plus postoperative BT (20-25Gray). Kaplan Meier survival curves were constructed and compared by log rank analysis (SPSS 21.0).
All 40 patients had preoperative XRT and total gross resection as part of the prospective trial, nineteen received BT (48%). Median follow-up was 106months. For the entire cohort, OS at 5 and 10years was 70% and 64%, respectively; RFS at 5 and 10years was 69% and 63%. RFS was significantly reduced in high versus low grade RPS at 5years (53% vs. 88%, p=0.016), but not at 10years (53% vs. 75%, p=0.079). RFS and OS at 10years were reduced in patients who presented with recurrent compared to primary disease (RFS 30% vs. 74%, p=0.015; OS 36% vs. 76%, p=0.036). At 10years, neither RFS nor OS was improved in patients who received BT compared to those who did not (RFS 56% vs. 69%, p=0.54; OS 52% vs.76%, p=0.23).
In this prospective trial with mature follow-up, long-term OS and RFS in patients who underwent combined preoperative XRT plus resection of RPS compare favourably with those reported in retrospective institutional and population-based series. Postoperative BT was associated with unacceptable toxicity and did not contribute to disease control.
In a prospective trial with mature follow-up, preoperative radiation combined with complete resection of retroperitoneal sarcoma resulted in favourable long-term RFS and OS compared to historical controls. Dose escalation with postoperative brachytherapy was not associated with better disease control.
To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS).
Patients received three cycles of HLI (14g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4Gy. Surgery was scheduled 4-6weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC_∗II_2004_003.
Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120mm (interquartile (IQ) range=82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8years (IQ range=3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06).
The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone.
This is a pure academic trial. No funding sources contributed to it.
Background:
Locoregional recurrence (LRR) rates following preoperative radiation therapy (RT) and radical resection for retroperitoneal sarcoma (RPS) are high. Targeted radiation dose escalation has been proposed as a means to decrease LRR, but is applicable only if LRRs are confined to within the RT field. We analyzed predictors for LRR and examined LRR locations to determine the potential benefit of dose escalation.
Methods:
For 33 patients treated with preoperative RT and radical resection, we determined high-risk tumor volumes appropriate for boost and identified the number of recurrences within this volume. Clinical and pathologic variables predictive of overall survival (OS), freedom from progression (FFP), LRR, and distant recurrence (DR) were evaluated.
Results:
Median follow-up was 32.9 months. At 1 and 3 years, OS was 87 and 64 %, FFP rates were 71 and 45 %, cumulative incidences of LRR were 19 and 37 %, and of DR were 13 and 21 %. On multivariate analysis, multifocal disease was a significant predictor of increased incidence of LRR. At first relapse, 6 patients had isolated LR, 2 isolated RR, 6 isolated DR, 1 synchronous LR and RR, and 1 synchronous LR, RR, and DR. Ultimately, 4 patients (25 % of those who recurred) had isolated in-field recurrences within the hypothetical high-risk dose-painting boost volumes and that thus might have been prevented with dose-escalation.
Conclusion:
Following preoperative RT and resection, LRR rates are high and associated with multifocal disease. Preoperative dose escalation to high-risk tumor volumes may perhaps benefit only a limited subset of patients, and therefore strategies are needed to select appropriate patients for consideration of this approach.
To compare three-dimensional conformal proton radiotherapy (3DCPT), intensity-modulated photon radiotherapy (IMRT), and 3D conformal photon radiotherapy (3DCRT) to predict the optimal RT technique for retroperitoneal sarcomas.
3DCRT, IMRT, and 3DCPT plans were created for treating eight patients with retroperitoneal or intra-abdominal sarcomas. The clinical target volume (CTV) included the gross tumor plus a 2-cm margin, limited by bone and intact fascial planes. For photon plans, the planning target volume (PTV) included a uniform expansion of 5 mm. For the proton plans, the PTV was nonuniform and beam-specific. The prescription dose was 50.4 Gy/Cobalt gray equivalent CGE. Plans were normalized so that >95% of the CTV received 100% of the dose.
The CTV was covered adequately by all techniques. The median conformity index was 0.69 for 3DCPT, 0.75 for IMRT, and 0.51 for 3DCRT. The median inhomogeneity coefficient was 0.062 for 3DCPT, 0.066 for IMRT, and 0.073 for 3DCRT. The bowel median volume receiving 15 Gy (V15) was 16.4% for 3DCPT, 52.2% for IMRT, and 66.1% for 3DCRT. The bowel median V45 was 6.3% for 3DCPT, 4.7% for IMRT, and 15.6% for 3DCRT. The median ipsilateral mean kidney dose was 22.5 CGE for 3DCPT, 34.1 Gy for IMRT, and 37.8 Gy for 3DCRT. The median contralateral mean kidney dose was 0 CGE for 3DCPT, 6.4 Gy for IMRT, and 11 Gy for 3DCRT. The median contralateral kidney V5 was 0% for 3DCPT, 49.9% for IMRT, and 99.7% for 3DCRT. Regardless of technique, the median mean liver dose was <30 Gy, and the median cord V50 was 0%. The median integral dose was 126 J for 3DCPT, 400 J for IMRT, and 432 J for 3DCRT.
IMRT and 3DCPT result in plans that are more conformal and homogenous than 3DCRT. Based on Quantitative Analysis of Normal Tissue Effects in Clinic benchmarks, the dosimetric advantage of proton therapy may be less gastrointestinal and genitourinary toxicity.
We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection.
Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin.
Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence.
Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease.
To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT).
From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15 Gy/9meV. EBRT dose varies between 45-50 Gy.
There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases.Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively.
EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.
The reported data on surgery plus radiotherapy for retroperitoneal soft tissue sarcomas (RPS) have been mostly from retrospective studies. We evaluated the long-term outcome of patients with operable RPS who were treated with protocol-based preoperative radiotherapy followed by complete surgical resection.
Data from two prospective trials that included preoperative radiotherapy and surgery for patients with radiographically resectable RPS were combined to define long-term relapse rates and survival.
Seventy-two patients with intermediate- or high-grade RPS were treated with preoperative radiotherapy (median dose, 45 Gy; range, 18.0-50.4 Gy). Fifty-four patients (75%) had primary RPS, whereas 18 (25%) had recurrent disease. The median tumor size was 15.5 cm. Sixty-four patients completed the planned preoperative radiotherapy; 57 (89%) underwent laparotomy with curative intent, and 54 (95%) had a macroscopically complete (R0 or R1) resection. With a median follow-up of 40.3 months, 28 patients (52%) who received preoperative radiotherapy and underwent a macroscopically complete resection had recurrences. For the 54 patients who underwent R0 or R1 resection after preoperative radiotherapy, the 5-year local recurrence-free, disease-free, and overall survival rates were 60%, 46%, and 61%, respectively. The median overall survival has not been reached (>60 months).
Patients with intermediate- or high-grade RPS treated with preoperative radiotherapy plus complete resection had a median survival >60 months. This compares favorably to historical data for similar patients treated with surgery alone.
Purpose: To evaluate the feasibility of Helical TomoTherapy for stereotactic radiosurgery, and to compare the dose conformity, dose uniformity, and dose gradient between plans of Helical TomoTherapy and step?and?shoot intensity?modulated radiotherapy(IMRT) generated by the NOMOS CORVUS system.. Method and Materials: Thirteen patients with intracranial tumors treated with stereotactic radiosurgery by step?and?shoot IMRT were analyzed.Tumor sizes varied from 1.45 cc to 40.78 cc. Two step?and?shoot IMRT treatment plans, one (IMRT I) with gantry angle restriction due to the existence of beam stopper at our institute and the other (IMRT II) with those constraints removed, were generated using the CORVUS system. Helical TomoTherapy treatment plans were generated for each case with identical anatomic contouring and prescription. The three plans were compared using dose conformity index, homogeneity index and dose gradient score index. Results:IMRT II plans without field angle constraints resulted in better dose conformity and steeper dose drop?off outside the targets compared to IMRT I with beam stopper restriction. Statistical analysis showed that TomoTherapy plans were better compared to the two step?and?shoot IMRT plans by dosimetric study. The average dose conformity index for TomoTherapy is 1.33 (range: 1.14 ? 1.60). For IMRT II plans, it is 1.39 (range: 1.17 ? 1.89). The dose gradient score index, with 100 being optimal, is 37.3 (range: 16.5 ? 52.7) for TomoTherapy plans, and 18.9 (range: ?31.1 ? 36.2) for IMRT II. Dose homogeneity index does not show statistical difference for the three treatment plans. The average treatment time for TomoTherapy plans is 47 minutes. Conclusion: TomoTherapy treatment planning showed significantly better results compared to the step?and?shoot IMRTtreatment planning in dose conformity and dose gradient for intracranial stereotactic radiosurgery. The treatment time using TomoTherapy was comparable to that using step?and?shoot IMRT.Conflict of Interest: Research partially supported by TomoTherapy Incorporated.
In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed.
For random samples of size N the product-limit (PL) estimate can be defined as follows: List and label the N observed lifetimes (whether to death or loss) in order of increasing magnitude, so that one has Then , where r assumes those values for which and for which measures the time to death. This estimate is the distribution, unrestricted as to form, which maximizes the likelihood of the observations.
Other estimates that are discussed are the actuarial estimates (which are also products, but with the number of factors usually reduced by grouping); and reduced-sample (RS) estimates, which require that losses not be accidental, so that the limits of observation (potential loss times) are known even for those items whose deaths are observed. When no losses occur at ages less than t the estimate of P(t) in all cases reduces to the usual binomial estimate, namely, the observed proportion of survivors.
Local recurrence remains the major cause of death in patients with retroperitoneal sarcoma (RPS). There is no consensus regarding management of patients with recurrent RPS.
We performed a retrospective review of patients with recurrent RPS managed at 2 tertiary care centers between 1983 and 2008. Presentation, treatments, and outcomes were analyzed.
Seventy-eight patients were identified and analyzed. Sixteen patients (22%) presented with concurrent metastatic disease; survival in this subset of patients was poor (median 12 months). Forty-eight patients underwent resection of the first local recurrence of RPS. Palliation of tumor-related symptoms was achieved in 79% with operation. Survival was significantly better in patients having complete (p = 0.001) and incomplete resection (p = 0.02) compared with patients having biopsy only. Among patients with first local recurrence, high grade tumor (p = 0.0001) and no resection (p = 0.007) were significantly associated with reduced survival. On multivariate analysis, radiation therapy, multifocality, histologic subtype, and time to local recurrence did not significantly correlate with survival. Second and third local recurrences occurred at shorter intervals compared with first local recurrence and were less likely to be completely resectable. Patients undergoing resection of second and third local recurrences had survival similar to that in patients undergoing resection of first local recurrence.
Tumor biology (high grade) is a significant prognostic factor for patients with recurrent RPS. Resection should be considered in patients with first and subsequent local recurrences (even if multifocal) of RPS because it is associated with improved survival. Operation should also be considered for palliation of symptoms in patients in whom resection is not possible.
To explore whether the adoption of a systematic attempt to perform wider resections may lead to prognostic improvements in retroperitoneal soft tissue sarcoma (RSTS).
Two hundred eighty-eight consecutive patients who were surgically treated at a single referral center were analyzed. Because a shift toward a systematic, more aggressive surgical approach (ie, liberal en bloc resection of adjacent organs) was in place from 2002 onward, patients were divided in two groups accordingly. Overall survival, crude cumulative incidence (CCI) of local recurrence, and distant metastases were estimated. Univariable and multivariable analyses were carried out.
Patients who underwent operation in the early period had a 5-year local recurrence rate of 48% compared with 28% for patients who were treated in the recent period. The number of distant metastases was greater in the recent group (22% v 13%), and overall survival was similar. In addition to the period of treatment, important independent determinants for local recurrence-free survival were histologic grade, histologic subtype, and radiation therapy. Overall, liposarcomas and grades 1 to 2 tumors had the greatest local benefit at 5 years.
In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.
Only 50% of patients with retroperitoneal sarcomas undergo complete resection and of these, 47% develop local tumor recurrence. To determine whether irradiation with dose escalation improves locoregional control, we reviewed the experience with adjuvant radiotherapy in the treatment of retroperitoneal sarcomas at the Fox Chase Cancer Center and the Hospital of the University of Pennsylvania.
Twenty-one patients with retroperitoneal sarcomas were treated with curative intent with surgical resection and radiation therapy at Fox Chase Cancer Center or the Hospital of the University of Pennsylvania between May 1965 and July 1992. Follow-up ranged from 14-340 months. Nineteen patients were treated postoperatively and 2 preoperatively. Radiation doses were between 36.0 Gy and 90.0 Gy (median 54.0 Gy).
The 2-year rates of local control and survival were 72% and 69%, respectively. Tumor size, stage, grade, and histology did not influence local control. Two of eight patients (25%) who received a total dose of > 55.2 Gy experienced local failure compared to 5 of 13 (38%) who received < or = 55.2 Gy. One patient experienced a small bowel obstruction that required surgical intervention. There were no other severe complications.
Postoperative treatment with radiotherapy using a dose > 55.0 Gy is recommended for patients with retroperitoneal sarcomas following surgical resection due to the significant likelihood of local recurrence. Innovative adjuvant radiation techniques to escalate doses to greater than 55.0 Gy including intraoperative radiation therapy, brachytherapy, or use of small bowel exclusion devices to reduce small bowel toxicity should be considered for retroperitoneal sarcomas.
Thirty-five patients with surgically resected sarcomas of the retroperitoneum were enrolled in a prospective, randomized, clinical trial comparing 20-Gy intraoperative radiotherapy in combination with postoperative low-dose (35- to 40-Gy) external-beam radiotherapy with postoperative high-dose (50- to 55-Gy) external-beam radiotherapy alone. Chemotherapy with doxorubicin hydrochloride, cyclophosphamide (anhydrous), and methotrexate sodium was used for a portion of the trial. Fifteen patients who received intraoperative radiotherapy and 20 control patients were followed up for a minimum of 5 years (median follow-up, 8 years). Median survival times were similar for the group that received intraoperative radiotherapy (45 months) and the control group (52 months). There were no indications of benefit from adjunctive chemotherapy. The number of locoregional recurrences was significantly lower among those who received intraoperative radiotherapy (six of 15) than control patients (16 of 20). Patients who received intraoperative radiotherapy had fewer complications of disabling radiation-related enteritis (two of 15) than control patients (10 of 20), but radiation-related peripheral neuropathy was more frequent among those who received intraoperative radiotherapy (nine of 15) than among control patients (one of 20).
This trial was performed to evaluate the impact of adjuvant brachytherapy on local and systemic recurrence rates in patients with soft tissue sarcoma.
In a single-institution prospective randomized trial, 164 patients were randomized intraoperatively to receive either adjuvant brachytherapy (BRT) or no further therapy (no BRT) after complete resection of soft tissue sarcomas of the extremity or superficial trunk. The adjuvant radiation was administered by iridium-192 implant, which delivered 42 to 45 Gy over 4 to 6 days. The two study groups had comparable distributions of patient and tumor factors, including age, sex, tumor site, tumor size, and histologic type and grade.
With a median follow-up time of 76 months, the 5-year actuarial local control rates were 82% and 69% in the BRT and no BRT groups (P = .04), respectively. Patients with high-grade lesions had local control rates of 89% (BRT) and 66% (no BRT) (P = .0025). BRT had no impact on local control in patients with low-grade lesions (P = .49). The 5-year freedom-from-distant-recurrence rates were 83% and 76% in the BRT and no BRT groups (P = .60), respectively. Analysis by histologic grade did not demonstrate an impact of BRT on the development of distant metastasis, despite the improvement in local control noted in patients with high-grade lesions. The 5-year disease-specific survival rates for the BRT and no BRT groups were 84% and 81% (P = .65), respectively, with no impact of BRT regardless of tumor grade.
Adjuvant brachytherapy improves local control after complete resection of soft tissue sarcomas. This improvement in local control is limited to patients with high-grade histopathology. The reduction in local recurrence in patients with high-grade lesions is not associated with a significant reduction in distant metastasis or improvement in disease-specific survival.
This randomized, prospective study assesses the impact of postoperative external-beam radiation therapy on local recurrence (LR), overall survival (OS), and quality of life after limb-sparing resection of extremity sarcomas.
Patients with extremity tumors and a limb-sparing surgical option were randomized to receive or not receive postoperative adjuvant external-beam radiotherapy. Patients with high-grade sarcomas received postoperative adjuvant chemotherapy whereas patients with low-grade sarcomas or locally aggressive nonmalignant tumors were randomized after surgery alone.
Ninety-one patients with high-grade lesions were randomized; 47 to receive radiotherapy (XRT) and 44 to not receive XRT. With a median follow-up of 9.6 years, a highly significant decrease (P2 = .0028) in the probability of LR was seen with radiation, but no difference in OS was shown. Of 50 patients with low-grade lesions (24 randomized to resection alone and 26 to resection and postoperative XRT), there was also a lower probability of LR (P2 = .016) in patients receiving XRT, again, without a difference in OS. A concurrent quality-of-life study showed that extremity radiotherapy resulted in significantly worse limb strength, edema, and range of motion, but these deficits were often transient and had few measurable effects on activities of daily life or global quality of life.
This study indicates that although postoperative external-beam radiotherapy is highly effective in preventing LRs, selected patients with extremity soft tissue sarcoma who have a low risk of LR may not require adjuvant XRT after limb-sparing surgery (LSS).
Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients.
Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12-15 Gy. Additional EBRT was given to 78% of patients to a dose of 45-50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140-160 Gy. The median follow-up was 33 months (range 1-77 mo).
The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease (p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%).
We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.
Surgical resection alone does not cure the majority of patients with retroperitoneal sarcoma (RPS). We evaluated the effects of preoperative external-beam radiotherapy (XRT) and postoperative brachytherapy (BT) combined with complete surgical resection.
Fifty-five patients with primary or locally recurrent RPS judged to be resectable were entered onto a trial of combined therapy and observed prospectively. Forty-six patients underwent complete gross resection with curative intent. Of these, 41 patients completed preoperative XRT and 23 patients received BT. Outcome measures were treatment toxicity, overall survival, and disease-free survival (DFS).
Preoperative XRT was very well tolerated and was associated with Radiation Therapy Oncology Group acute toxicity scores of < or = 2 in all patients. Acute postoperative and BT-related toxicity resulted in modified RTOG scores of > or = 3 in 39.1% (18 of 46) of patients. Late toxicity was associated with death in 4.3% (2 of 46) and with life-threatening illness in 2.2% (1 of 46) of patients, all of whom had been treated with BT to the upper abdomen. The 2-year overall survival and DFS for resected RPS were 88% and 80%, respectively. Significantly better 2-year DFS was achieved in patients with primary RPS and in those with low-grade tumors (93% and 95%, respectively).
The initial results of combined therapy are promising. Although preoperative XRT was very well tolerated, BT to the upper abdomen was associated with substantial toxicity. Our current protocol includes selective application of BT to the lower abdomen only.
To evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival.
Between January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control.
The actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p = 0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p = 0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs. 52% for patients with positive margins at 5 years, p = 0.04). Gender was borderline significant (85% for female patients vs. 54% for male patients at 5 years, p = 0.06). On multivariate analysis, only surgical margin status remained significant (p = 0.032). The distant metastasis-free survival rate at 5 and 10 years was 58% and 54%, respectively. The median time to distant metastases was 15.6 months. The lungs were the most common site of metastases. The only significant factor associated with distant metastasis-free survival was local control (73% for patients with locally controlled tumors vs. 19% for patients with local recurrence at 5 years, p = 0.0013). The actuarial 5- and 10-year overall survival rate was 56% and 47%, respectively. Gender (74% for female patients vs. 37% for male patients at 5 years), surgical margin status (66% for patients with negative or close margins vs. 48% for patients with positive margins at 5 years), and local control (64% for patients with locally controlled tumors vs. 21% for patients with uncontrolled primary tumors at 5 years) were significant predictors on both univariate and multivariate analyses (p <0.05).
The results of this study demonstrate the paramount importance of local control and complete surgical resection in the management of soft-tissue sarcoma of the retroperitoneum and deep trunk.
The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS).
Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy).
Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections.
Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.
In the management of retroperitoneal sarcomas it is necessary to achieve local control to ensure survival. The role of adjuvant radiation therapy (RT), either pre- or postoperative, remains controversial.
Outcomes for 40 patients with retroperitoneal sarcoma treated with surgery and postoperative RT (n = 25) or preoperative RT (n = 15) were analyzed for variables prognostic for local control, survival, and associated complications.
Patterns of failure for patients treated by resection and postoperative RT were local (n = 4), local and distant (n = 3), and distant (n = 3). The failure patterns for preoperative RT cases were local (n = 2), local and distant (n = 2); and distant (n = 4). Median time to local recurrence in the postoperative and preoperative RT series were 1 year and 2.5 years respectively. The margin status was predictive for local control (P = 0.0065) and survival (P = 0.0012), regardless of treatment sequence. Absolute 5-year survival was 12% with positive margins versus 69% if negative. Histologic grade was indicative of the risk for distant metastasis (low grade 8% vs high grade 64%; P = 0.1373), and significantly predicted 5-year absolute survival (low grade 77% vs high grade 34%; P = 0.0267). Postoperative RT was associated with significant complications (infection, hemorrhage, and bowel obstruction--2 cases each).
Compared with the surgery-alone series, adjuvant RT appears to improve the probability of local control. Preoperative RT may be the preferred sequence potentially to improve tumor resectability and local-regional control with less risk of complications than with postoperative RT.
Retroperitoneal sarcomas (RPSs) are rare tumors with poor survival rates due to difficult resectability and high local and distant recurrence rates. Preoperative radiation therapy appears to have dosimetric advantages to utilize the tumor as a tissue expander to limit exposure of small bowel to higher radiation doses.
Between June 1999 and December 2003, 16 consecutive patients with biopsy-proven RPS were treated with preoperative radiation with selective dose escalation. This included 45 grays (Gy) in 25 fractions to the entire tumor plus margin and a boost dose of 57.5 Gy to the volume predicted as high risk for positive surgical margins. Treatment toxicity and local control were evaluated prospectively as primary endpoints. The secondary goal was the theoretical calculation of future dose escalation and feasibility. Each patient underwent laparotomy. Tumor response was judged using computed tomography (CT) scan and by necrosis on final pathology. Theoretical treatment plans evaluated the potential for additional radiation dose escalation.
All patients completed the radiation protocol. The most common acute side effects were nausea/vomiting, which affected 4 patients (25%), with only 1 patient requiring inpatient intravenous hydration. There was no severe late postoperative morbidity or mortality. Twelve tumors (75%) decreased in maximum dimension, with a median decrease of 9.4%. Fourteen of 16 patients (88%) underwent complete macroscopic resection. With a median follow-up of 28 months (range, 7-52 months), there were only 2 local recurrences. The actuarial 2-year local control rate was 80%. Theoretical treatment plans suggest that significant dose escalation (up to 80 Gy) may be possible.
Preoperative radiation therapy with selective dose escalation to the margin at risk is tolerable and allows higher radiation dose to the volume judged to be at greatest risk for local tumor recurrence.
To compare step-and-shoot intensity-modulated radiation therapy (SAS-IMRT) and helical tomotherapy (Tomo) dosimetry plans for patients who have received adjuvant radiation therapy for retroperitoneal sarcomas (RSTS).
A retrospective review was performed for seven patients who received either SAS-IMRT or Tomo as adjuvant radiation therapy for RSTS. In each case, a treatment plan of the other modality was generated so that SAS-IMRT and Tomo could be compared.
The average percentage of clinical target volume (CTV) that received less than the prescription dose was 1.4% for Tomo compared to 3.8% for SAS-IMRT. Both SAS-IMRT and Tomo plans provided comparable and significant reductions in volume of small bowel receiving greater than 45 Gy compared to simple opposing standard radiation fields. For the ipsilateral kidney, Tomo significantly reduced the volume of kidney that received at least 15 Gy (average 22% for Tomo vs. 56% for SAS-IMRT).
Both SAS-IMRT and Tomo can encompass the large CTV often required for patients with RSTS, although Tomo provides superior dose uniformity. Both SAS-IMRT and Tomo can minimize the volume of small bowel receiving greater than 45 Gy. Tomo was superior to SAS-IMRT in minimizing the volume of ipsilateral kidney irradiated to greater than 15 Gy when the CTV is adjacent to a kidney. Dose escalation and target margin expansion may thus become realistic possibilities.
To determine the long-term outcomes after multimodality treatment of retroperitoneal, pelvic, and deep truncal sarcomas and to identify the factors associated with local control (LC), distant metastasis (DM), and overall survival (OS).
A total of 85 patients with retroperitoneal, pelvic, and deep truncal sarcomas were treated with radiotherapy (RT) between 1987 and 2005. A retrospective analysis of LC, DM, and OS was conducted using log-rank and Cox regression statistical methods.
The 2- and 5-year LC, DM, and OS rates were 66% and 51%, 38% and 58%, and 70% and 34%, respectively. Negative surgical margins and a higher radiation dose were associated with greater LC rates on both univariate and multivariate analyses, and female gender was significantly associated with greater LC on multivariate analysis only. None of the analyzed risk factors was significantly associated with DM, although patients with high-grade tumors showed a trend toward an increased risk of DM. Gross residual disease after resection and high tumor grade were associated with worse OS rates on univariate and multivariate analyses, and male gender was significantly associated with worse OS on multivariate analysis only. A time-dependent analysis of LC in relation to DM demonstrated that patients with local failure had a hazard ratio of 19.7 for DM compared with patients without local failure (p < 0.0001). Of the 85 patients, 5 and 8, respectively, had clinically significant acute and late toxicity.
The results of this study emphasize the importance of LC in patients with retroperitoneal sarcoma. Radiation dose escalation or radiosensitization strategies to enhance LC are warranted.
Common Terminology Cri-teria for Adverse Events v4
- Dctd
- Nci
- Dhhs Nih
Cancer Therapy Evaluation Program. Common Terminology Cri-teria for Adverse Events v4.0, DCTD, NCI, NIH, DHHS. http:// ctep.cancer.gov/protocolDevelopment/electronic_applications/ docs/ctcae_index.pdf#search =''commonterminology''. Updated April 15, 2010. Accessed June 4, 2010.
Adjuvant radiation therapy for resectable retroperitoneal soft tissue sarcoma: The University of Florida experience
- Ra Zlotecki
- Katz
- Morris Ts
- Cg
Zlotecki RA, Katz TS, Morris CG, et al. Adjuvant radiation therapy for resectable retroperitoneal soft tissue sarcoma: The University of Florida experience. Am J Clin Oncol 2005;28: 310–316.