Clinical Evaluation and Treatment of Soft Tissue Tumors





Although soft tissue sarcomas are a heterogeneous group of neoplasms, their clinical evaluation and treatment follow common principles. This chapter focuses on the clinical evaluation, determinants of prognosis and outcome, and treatment of patients with soft tissue sarcoma.


Anatomically, the extremity is the most common anatomic site for soft tissue sarcoma, accounting for approximately half of all cases. Other important anatomic sites include the retroperitoneum, head and neck, and body wall. The site-specific distribution of histologic subtypes is outlined in Fig. 2.1 . Of note, the distribution of histologic subtypes depends greatly on the anatomic site; for example, in the extremities, undifferentiated pleomorphic sarcoma, liposarcoma, and synovial sarcoma are common. In contrast, in the retroperitoneum, synovial sarcoma and undifferentiated pleomorphic sarcoma are relatively uncommon; other histologic subtypes, particularly leiomyosarcoma and liposarcoma, predominate. The reasons for this regional variation in histologic subtype are not understood.




Fig. 2.1


Anatomic distribution and site-specific histologic subtypes of 7563 consecutive soft tissue sarcomas seen at the University of Texas MD Anderson Cancer Center. UPS, undifferentiated pleomorphic sarcoma (∗previously, malignant fibrous histiocytoma, MFH).

From MDACC Sarcoma Database, June 1996 to June 2006.


Clinical Evaluation


Clinical Presentation and Assessment


Most patients with suspected soft tissue neoplasms present with a painless mass, although pain is reported in one-third of cases. A delay in diagnosis is common; the most common misdiagnoses include posttraumatic or spontaneous hematoma and lipoma. A late diagnosis of patients with retroperitoneal sarcomas is common because of the large size of the retroperitoneal space, generally slow growth rate, and the tendency of sarcomas to gradually displace rather than to invade and compromise adjacent viscera. Therefore, retroperitoneal sarcomas can reach a considerable size before the diagnosis ( Fig. 2.2 ).




Fig. 2.2


Contrast-enhanced CT scan of a 52-year-old patient with retroperitoneal dedifferentiated liposarcoma. The CT findings illustrate features of both well-differentiated and dedifferentiated forms of liposarcoma that frequently coexist. The dedifferentiated component is the more solid-appearing, low-density mass situated in the right retroperitoneum, whereas the well-differentiated component has similar density to the subcutaneous (normal) fat and fills the retroperitoneum, displacing the contrast-filled small bowel to the anatomic left side and posterior.


The physical examination should include an assessment of tumor size, relative mobility, and fixation. Patients with extremity soft tissue tumors should be evaluated for tumor-related neuropathy. An examination of regional lymph node basins should also be performed, with the understanding that nodal metastases are relatively uncommon, occurring in less than 15% of patients with extremity soft tissue sarcoma. Functional assessment of the involved region is of paramount importance, as well as complete neurologic and vascular examinations.


Pretreatment Evaluation


The pretreatment evaluation of the patient with a suspected soft tissue malignancy includes a biopsy diagnosis and radiologic staging to establish the extent of the disease. Practical nomograms and algorithms for the evaluation of patients with extremity and retroperitoneal soft tissue masses are outlined in Figs. 2.3 and 2.4 .




Fig. 2.3


A, Nomogram for overall survival. B, Nomogram for distant metastases.

Reproduced with permission of The Lancet Ltd. From Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 2016;17(5):671–680.



Fig. 2.4


Pretreatment evaluation, staging, and treatment algorithm for assessment of the patient presenting with a retroperitoneal (nonvisceral) mass. Patients should undergo pretreatment cross-sectional imaging by CT or MRI. Localized, radiologically resectable masses believed to be neoplastic can be treated by diagnostic and therapeutic primary tumor resection. In clinical settings, where preoperative treatment protocols are available, pretreatment image-guided core-needle biopsy (CNB) should be used to establish the diagnosis of sarcoma for protocol eligibility. Patients with locally advanced (radiologically unresectable) or metastatic disease should undergo CNB for diagnosis followed by consideration of nonsurgical treatments. In general, CNB is sufficient for diagnosis, and surgery performed exclusively for diagnostic purposes (e.g., laparotomy for incisional biopsy) should be avoided whenever possible.


Biopsy.


A pretreatment biopsy of the primary tumor is essential for most patients presenting with soft tissue masses. In general, any soft tissue mass that is enlarging or is greater than 5 cm should be considered for biopsy. For more anatomically constrained areas such as the forearm and hand, lesions less than 5 cm should be considered for biopsy. The preferred biopsy method is generally the least invasive technique that allows for a definitive histologic assessment, including an assessment of grade. Grade is particularly important to clinicians because it impacts treatment planning and treatment options. Grading of soft tissue sarcomas is discussed in Chapter 1 .


A percutaneous core-needle biopsy (CNB) provides satisfactory diagnostic tissue for the diagnosis of most soft tissue neoplasms. A CNB can be performed “blindly” in the clinic by clinicians without real-time radiologic control. However, many centers have moved to an image-guided CNB performed by interventional radiologists. Image-guided approaches allow for a biopsy from the areas of the tumor believed to be most likely to harbor viable tumor (i.e., avoiding centrally necrotic areas). The use of real-time imaging also minimizes the risks for biopsy-related vascular or adjacent organ injury. In many centers, image-guided biopsy also allows for real-time pathology quality control by having a pathologist immediately available in the biopsy suite to evaluate the quality of tissue retrieved and its probable suitability for a definitive diagnosis. Studies comparing a CNB to the traditional open surgical biopsy have demonstrated the safety, reliability, and cost-effectiveness of this approach. Additional issues related to the pathologic interpretation of core-needle biopsies are discussed in Chapter 5 .


Tumor recurrence in the needle track after a percutaneous CNB is extremely rare. Indeed, there are only case reports in the literature. However, these rare cases have led some physicians to advocate tattooing the biopsy site for subsequent excision. Most experienced sarcoma surgeons take a practical approach to this issue and perform an en bloc resection of the needle track and percutaneous entry point when feasible, but not if a resection of the biopsy track requires a second incision or substantial modification of the surgical plan. The low risk of needle track recurrence does not justify the added morbidity risk imposed by major alterations in the surgical plan.


An incisional biopsy is occasionally required to establish a definitive diagnosis for some soft tissue neoplasms. It has the advantage over CNB of providing more tissue for pathologic analysis and often additional tissue for tumor banking or research purposes. However, the morbidity associated with an incisional biopsy can be considerable, including the risks for anesthesia, bleeding, and wound-healing problems. Furthermore, if additional cores can be obtained, CNB may suffice to facilitate research. Given these considerations and its greater cost, incisional biopsy is generally a secondary technique best reserved for cases where a definitive diagnosis cannot be established by CNB.


An excisional biopsy may be appropriate for some patients who present with small, superficial neoplasms located on the extremities, well away from critical structures, or the superficial body wall, where the morbidity from this procedure is minimal. Although an excisional biopsy may allow for a single diagnostic and therapeutic procedure in some clinical settings, its main disadvantage is that the malignant potential of the neoplasm is unknown at biopsy, and informed decisions on surgical margins are not possible. This leaves the operating surgeon with the choice of narrow or nonexistent surgical margins, with generally lower risks for wound and functional morbidity, or deliberately wide margins, with generally greater risks for wound and functional morbidity. The oncologic appropriateness of the surgical margin cannot be assessed preoperatively and is difficult to assess with precision intraoperatively. This disadvantage makes an excisional biopsy appropriate for only a small subset of patients who have small, superficial neoplasms and for whom a reexcision is feasible, if the final diagnosis indicates a malignant lesion with compromised margins.


A percutaneous fine-needle aspiration (FNA) biopsy can also be used for cytologic assessment of some soft tissue neoplasms. Accurate FNA diagnosis requires the availability of an expert cytopathologist experienced in the diagnosis of soft tissue sarcomas by cytology. From a practical standpoint, most centers (even academic centers) will not have a cytopathologist with sufficient experience to allow for the use of FNA for routine diagnosis and classification of primary soft tissue neoplasms. Additionally, even with experience, a risk of diagnostic error remains because the histologic architecture is not captured with FNA. Given the frequent difficulty in histopathologic diagnosis and classification of soft tissue sarcoma, the major utility of FNA cytology in most centers is for the diagnosis of patients with suspected recurrent sarcoma. In this setting, there is already an established pathologic diagnosis, such that only confirmation of a recurrence with similar features is required.


Staging.


The relative rarity of soft tissue sarcoma, the anatomic heterogeneity of these lesions, and the presence of more than 100 recognized histologic subtypes, of variable grades, have made it difficult to establish a functional system that can accurately stage all forms of this disease. The staging system (8th edition) of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC; formerly International Union Against Cancer) is the most widely used staging system for soft tissue sarcoma (see Chapter 1 ). The system is designed for optimal staging of extremity tumors but is also applicable to the torso, head and neck, and retroperitoneal lesions; it should not be used for sarcomas of the gastrointestinal tract or other parenchymal organs.




Prognostic Factors


Clinicopathologic Factors


Understanding the clinicopathologic factors that affect outcome is essential in formulating a treatment plan for the patient with soft tissue sarcoma. The three major clinicopathologic factors that establish the risk profile for a given patient are tumor size, histologic grade, and extent of disease (nodal or metastatic involvement), as reflected in the 8th edition of the AJCC staging system. The size of the tumor is now especially emphasized, with tumors grouped as 5 cm or less, greater than 5 cm, greater than 10 cm, and greater than 15 cm.


In addition to the previous factors, histologic subtype and margin status are also significant, but this information is not captured by the current staging system. Moreover, unlike other solid tumors, factors that predict local recurrence differ from those that predict distant metastasis and tumor-related death ( Table 2.1 ). In other words, patients with a constellation of adverse prognostic factors for local recurrence are not necessarily at increased risk for distant metastasis or tumor-related death, and vice versa. Therefore, clinicians and pathologists should be careful about using the terminology “high-risk disease” without qualification of the end point (i.e., local recurrence or overall survival) for which the patient is believed to be at increased risk.



Table 2.1

Multivariate Analysis of Prognostic Factors in Patients with Extremity Soft Tissue Sarcoma

From Pisters PW, Leung DH, Woodruff J, et al. Analysis of prognostic factors in 1041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14(5):1679−1689.







































































End Point Adverse Prognostic Factor Relative Risk (%)
Local recurrence Fibrosarcoma 2.5
Local recurrence at presentation 2.0
Microscopically positive margin 1.8
Malignant peripheral nerve sheath tumor 1.8
Age >50 yr 1.6
Distant recurrence High grade 4.3
Deep location 2.5
Size 5.0–9.9 cm 1.9
Leiomyosarcoma 1.7
Nonliposarcoma histology 1.6
Local recurrence at presentation 1.5
Size ≥10.0 cm 1.5
Disease-specific survival High grade 4.0
Deep location 2.8
Size ≥10.0 cm 2.1
Malignant peripheral nerve sheath tumor 1.9
Leiomyosarcoma 1.9
Microscopically positive margin 1.7
Lower-extremity site 1.6
Local recurrence at presentation 1.5

Adverse prognostic factors identified are independent by Cox regression analysis.


Classification and Prognostic Significance of Surgical Margins


Surgeons should use the UICC resection (designated by the letter R ) classification system for integration of the operative findings and the final microscopic surgical margins. Under this system, an R0 resection is defined as a macroscopically complete sarcoma resection with microscopically negative surgical margins; an R1 resection is a macroscopically complete sarcoma resection with microscopically positive surgical margins, and an R2 resection is a macroscopically incomplete (i.e., with gross residual disease) sarcoma resection with microscopically positive surgical margins.


All therapeutic surgical procedures should be described in medical records using the R classification. To do so, surgeons must await the final pathology report, including margin assessment, and then integrate the observed operative findings, including the presence or absence of a residual gross tumor, with the final assessment of microscopic surgical margins. The operative report, discharge summary, and related medical records should describe the procedure using the R classification. As an example, a surgical procedure that involved a wide local resection of a left anterior thigh soft tissue leiomyosarcoma with satisfactory gross tumor margins, no operatively defined residual gross tumor, and negative microscopic surgical margins would be described as “R0 resection of left anterior thigh leiomyosarcoma.”


The type of microscopically positive surgical margins also appears important. For example, an R1 resection for a low-grade liposarcoma or an R1 after preoperative radiation treatment in which a microscopically positive margin is anticipated (and accepted) in order to preserve critical structures has a relatively low risk (<10%) for local recurrence. Furthermore, an anticipated positive margin on a critical structure does not increase local recurrence rates, as described in the Toronto Margin Context Classification (TMCC). Using the TMCC, positive margins are separated into planned close but positive at critical structures, positive after an unplanned surgical resection or reexcision, and inadvertent positive margins.


Patients undergoing “unplanned” excision followed by a reexcision with positive margins (i.e., R1 re-resection) or patients with unanticipated positive margins after primary resection are at increased risk for local recurrence, with rates approaching 30%. Therefore the specific clinical setting needs to be considered when interpreting the relative risk for local recurrence after an R1 resection.


Nomograms for Assessment of Individual Patient Prognosis


Several prognostic nomograms have been developed for patients with soft tissue sarcomas in the extremity and retroperitoneum. The results have been used to construct and internally validate a nomogram to predict sarcoma-specific death ( Fig. 2.5 ). These nomograms match a patient’s prognostic score against those of previously treated patients with comparable tumor and clinical factors to estimate individual patient risk for sarcoma-related death.




Fig. 2.5


Postoperative nomogram for 12-year sarcoma-specific deaths in 2163 patients treated at the MSKCC. Fibro, Fibrosarcoma; Lipo, liposarcoma; Leiomyo, leiomyosarcoma; MPNST, malignant peripheral nerve sheath tumor; SSD, sarcoma-specific death; UPS, undifferentiated pleomorphic sarcoma (∗formerly called malignant fibrous histiocytoma, MFH).

From Kattan MW, Leung DH, Brennan MF. Postoperative nomogram for 12-year sarcoma-specific death. J Clin Oncol 2002;20(3):791−796.




Treatment of Localized Primary Extremity Sarcomas


Surgery


Surgical resection remains the cornerstone of therapy for localized primary soft tissue sarcoma. This discussion focuses on soft tissue sarcoma in the limbs, the most common anatomic site of origin, but the principles of treatment are generally applicable for patients with sarcomas at other anatomic sites.


While historically regarded as the primary treatment of extremity soft tissue sarcoma, amputation has now become much less common. Improvements in advanced imaging have also enabled a better understanding of the anatomic extent of the tumor and its viability in relation to critical structures. With the widespread application of multimodality treatment strategies, the vast majority of patients with localized soft tissue sarcoma of the extremities undergo limb-sparing treatment, and less than 10% of patients presently undergo amputation.


Satisfactory local resection involves resection of the primary tumor with a margin of normal tissue around the lesion. Dissection along the tumor pseudocapsule ( enucleation or “shelling out”) is associated with local recurrence rates ranging between 33% and 63%.


In contrast, wide local excision with a margin of normal tissue around the lesion is associated with lower local recurrence rates in the range of 10% to 31%, as demonstrated in the surgery-alone control arms of randomized trials evaluating postoperative radiotherapy (RT) and in single-institution reports.


The issue of what constitutes an acceptable gross surgical margin is complex, with limited prospective data specifically addressing surgical margins in soft tissue sarcoma surgery. The ongoing Children’s Oncology Group prospective study investigating neoadjuvant chemotherapy in children and young adults with nonrhabdomyosarcoma soft tissue sarcoma hopes to address this using data collected on the quantity and quality of the margin. Nonetheless, circumferential margin assessment in sarcomas is imprecise because of the complex anatomy of each tumor, as well as the tendency of soft tissue around the tumor to collapse and adopt its inherent shape when not under the continuous tension that is applied to the tissues as part of modern soft tissue surgery. This can result in significant discordance between the intraoperative perception and the pathologic evaluation of the gross surgical margin.


At sarcoma centers with experienced surgeons, in order to do limb-sparing resections in particularly challenging cases and in the setting of preoperative radiotherapy, occasionally a “planned positive margin” is accepted. This occurs intentionally when the surgeon dissects along critical neurovascular structures to maintain a functioning limb, anticipating a possible microscopic positive margin. Recurrence rates with this attentive technique approach those of true R0 resections.


Unlike resections for cutaneous melanoma in which gross surgical margins can be measured with a ruler at surgery, a gross margin assessment for soft tissue sarcoma cannot be measured so precisely. In addition, it is likely that not all soft tissues provide an equivalent barrier to tumor extension. For example, it is believed that a smaller gross margin that includes a fascial barrier is generally a more secure margin than a comparable gross margin that does not include fascia. For these reasons, a margin assessment for sarcomas by both surgeons and pathologists will continue to have an unavoidable degree of imprecision that probably exceeds the inherent imprecision in the assessment of gross margins of other solid tumors.


Combined-Modality Limb-Sparing Treatment.


Currently, greater than 90% of patients with localized extremity sarcomas undergo limb-sparing treatment. The use of limb-sparing multimodality treatment approaches for extremity sarcoma was based on an important Phase III trial from the U.S. National Cancer Institute (NCI) in which patients with extremity sarcomas amenable to limb-sparing surgery were randomly assigned to receive amputation or limb-sparing surgery with postoperative RT.


Both arms of this trial included postoperative chemotherapy with doxorubicin, cyclophosphamide, and methotrexate. With more than 9 years of follow-up data, this study established that for patients for whom limb-sparing surgery is an option, limb-sparing surgery combined with postoperative RT and chemotherapy yielded disease-related survival rates comparable to those for amputation and simultaneously preserved a functional extremity.


This trial established limb-sparing treatment as the standard treatment for patients with localized extremity soft tissue sarcoma. Amputation is used in only clinical settings where local tumor anatomy precludes limb-sparing approaches, most often as a result of tumor involvement of functionally significant neurovascular structures.


Currently, a discussion of limb-preserving approaches must be linked to a discussion of the role of adjuvant therapies, most frequently radiation treatment. Several randomized controlled trials have addressed issues surrounding the use of adjuvant therapy and collectively have established important milestones in the evolution of the local management of soft tissue sarcoma.


Yang et al. randomized 91 patients with high-grade extremity lesions after limb-sparing surgery to receive adjuvant chemotherapy alone or concurrent chemotherapy and RT. An additional 50 patients with low-grade tumors were to receive adjuvant RT or no further treatment after limb-sparing surgery. The local control rate for those who received RT was 99% compared to 70% in the non-RT group ( P <0.0001). The results were similar for high- and low-grade tumors ( Table 2.2 ).



Table 2.2

Phase III Trials of Adjuvant Radiotherapy for Localized Extremity and Trunk Sarcoma Stratified by Grade











































































Histologic Grade First Author/Institution Treatment Group Radiation Dose, Gy No. of Patients No. of Local Failures (%) LRFS (%) OS (%)
High grade Pisters/MSKCC Surgery + BRT 42-45 56 5 (9) 89 27
Surgery 63 19 (30) 66 67
Yang Surgery + XRT 45 + 18 (boost) 47 0 (0) 100 75
Surgery 44 9 (20) 78 74
Low grade Pisters Surgery + BRT 42-45 22 8 (36) 73 96
Surgery 23 6 (26) 73 95
Yang Surgery + BRT 45 + 18 (boost) 26 1 (4) 96 NR
Surgery 24 8 (33) 63 NR

MSKCC, Memorial Sloan-Kettering Cancer Center; BRT, brachytherapy; LRFS, local recurrence-free survival; OS, overall survival; NCI, National Cancer Institute; XRT, external-beam radiotherapy; NR, not reported.


Adjuvant radiation using brachytherapy (BRT) has also been evaluated. High-dose-rate brachytherapy (HDR BRT) can yield acceptable results when there is a high risk of a compromised surgical margin and no planned complex soft tissue reconstruction.


In one study, patients with localized extremity and superficial trunk sarcomas undergoing surgery were randomly assigned to be treated by surgery alone or by a combination of surgery and BRT. BRT was administered postoperatively through an iridium-192 implant that delivered 42 to 45 Gy over 4 to 6 days. At 5 years, the local control rate for high-grade tumors was 91% with BRT compared to 70% in surgery-alone controls ( P <0.04). Of note, no improvement in local control with BRT was evident for patients with low-grade tumors. The local control rate was 74% with surgery alone and 64% with BRT. The full explanation for grade-specific differences in local control with BRT remains unresolved, although one suggestion implicates the relatively long cell cycle of low-grade tumors; low-grade tumor cells may not enter the radiosensitive phases of the cell cycle during the relatively short BRT time.


These studies have provided the evidence to support surgery plus radiation as the standard approach for most patients with operable extremity and superficial trunk sarcomas. At this time, there are no controlled trials evaluating the use of radiation treatment for patients with sarcomas in nonextremity sites. However, most multidisciplinary groups have extrapolated from the foregoing data and have assumed that radiation improves local control for patients with nonextremity sarcomas as well.


Treatment by Surgery Alone—without Radiotherapy.


Radiation provides the unquestioned clinical benefit of decreasing local recurrence for the majority of patients with soft tissue sarcoma. However, the known secondary adverse effects of radiation, which include edema, fibrosis, and radiation-induced second malignancies, have also prompted clinicians to try to identify a subset of patients who could be treated by surgery alone without compromising local disease control. Careful patient selection for unimodality treatment by surgery alone is essential. Important criteria include an R0 resection in clinical settings where the anatomic site clearly allows for adequate surgical margins. The importance of anatomic site in considering treatment by surgery alone is illustrated by the hypothetical cases of two patients with 4-cm, high-grade sarcomas: one in the anterior thigh and the second case with an identically sized tumor located in the wrist. Clearly, the first patient could undergo satisfactory treatment by surgery alone because the surgical margins can and should be satisfactory. However, this is not the case for the second patient because the wrist or other anatomically similar site is not amenable to wide margins without amputation and sacrifice of neurovascular structures. Table 2.2 summarizes recent reports of patients treated by surgery alone.


Amputation.


Although sparingly used, amputation is still the appropriate treatment for a subset of patients who present with locally advanced primary tumors. The criteria for patient selection for amputation include the following:




  • Radiologically defined major vascular, bony, or nerve involvement, such that a “limb sparing” primary tumor resection will result in critical loss of function or tissue viability.



  • Localized nonmetastatic disease (amputation is usually not considered for patients with established metastatic disease).



  • When a sarcoma extensively involves the foot and ankle, a below-knee amputation may lead to a more ideal functional result than a limb-sparing surgery, especially if radiation is involved. This decision is certainly discretionary.



For patients without limb-sparing surgical options, amputation offers excellent local tumor control and the prospect of prompt rehabilitation; therefore a small but well-defined role remains for amputation in the management of patients with extremity soft tissue sarcoma.


Management of Regional Lymph Nodes


There is no role for routine regional lymph node dissection in most patients with localized soft tissue sarcoma, given the low (2% to 5%) incidence of lymph node metastasis in adults with sarcomas.


However, patients with angiosarcoma, embryonal/alveolar rhabdomyosarcoma, clear cell sarcoma, and epithelioid sarcoma are at increased risk for lymph node metastasis and should be carefully examined for lymphadenopathy. These patients should be considered for either positron emission tomography (PET) scan or sentinel lymph node biopsy as part of definitive treatment. A therapeutic lymph node dissection should be considered for patients with pathologically proven lymph node involvement who do not have radiologically defined metastatic disease. A therapeutic lymph node dissection may result in survival rates as high as 34%.


The prognosis of patients with pathologically positive metastatic disease to lymph nodes has been generally regarded as similar to patients with visceral metastatic disease. However, one study described a series of patients with isolated lymph node metastasis treated intensively with combined-modality treatment showing somewhat better outcomes, approaching those of patients with localized, high-risk (stage III) disease. However, controversy remains because lymph node involvement has also been shown to confer a poor prognosis. Accordingly, in the latest AJCC staging system, N1 is designated stage IV.


Radiotherapy


Rationale for Combining Radiotherapy with Surgery.


The use of RT in combination with surgery for soft tissue sarcoma is supported by two Phase III clinical trials (see Table 2.2 ) and is based on two premises: (1) microscopic foci or residual disease can be destroyed by RT, and (2) less radical surgery can be performed when surgery and RT are combined. Although the traditional belief was that soft tissue sarcoma is resistant to RT, radiosensitivity assays performed on sarcoma cell lines grown in vitro have confirmed that the radiosensitivity of sarcomas is similar to that of other malignancies; this confirmation supports the first premise. The second premise stresses the philosophy of preservation of form (including cosmesis where possible) and function as a goal for many patients with extremity, truncal, breast, and head and neck sarcomas. Similar principles govern the frequent use of RT for sarcomas at anatomically challenging sites, such as the retroperitoneum, head and neck, or paravertebral regions.


Sequencing of Radiotherapy and Surgery.


The optimal sequencing of surgery and radiation is controversial. Advantages of preoperative radiation include a generally lower radiation dose (50 Gy) and small field size, with reduced risks for long-term treatment sequelae, including edema and fibrosis. These advantages occur at the cost of increased risk for surgical wound complications resulting from radiation-related impairment in wound healing. Advantages of postoperative radiation treatment include the ability to treat pathologically diagnosed and staged patients with known margin status. However, postoperative radiation is usually administered at a higher dose (65 Gy) and is associated with greater risks for treatment-related, long-term complications, including edema and fibrosis. Therefore, treatment sequencing involves complicated trade-off issues that need to be individualized and carefully discussed with the patient.


The NCI of Canada/Canadian Sarcoma Group SR2 clinical trial ( Fig. 2.6 ) provided a prospective randomized comparison of preoperative versus postoperative RT. Patients were randomly assigned to be treated by surgery with either preoperative or postoperative radiation (with a radiation boost dose for patients with microscopically positive surgical margins). The primary end point of the trial was major wound complications. The SR2 trial demonstrated that wound complications were twice as common with preoperative RT as with postoperative RT (35% vs. 17%, respectively), although the increased risk was almost exclusively confined to patients with sarcomas of the lower extremity. Other studies have supported these findings.


Mar 10, 2020 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Clinical Evaluation and Treatment of Soft Tissue Tumors
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