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Early Outcomes of Preoperative 5-Fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection

Open AccessPublished:June 29, 2020DOI:https://doi.org/10.1016/j.adro.2020.06.024

      Abstract

      Purpose

      There are limited data regarding the use of hypofractionated radiation therapy (RT) for soft tissue sarcoma. We report early oncologic outcomes and wound complications of patients undergoing preoperative hypofractionated (5 fraction) RT followed by immediate surgical resection.

      Methods and Materials

      An institutional review board–approved database of patients treated with preoperative RT for soft tissue sarcoma was queried. Patients treated with a hypofractionated dosing regimen followed by immediate (within 7 days) planned wide surgical resection were identified.

      Results

      Between 2016 and 2019, 16 patients met eligibility criteria. The median patient age was 64 years old (range, 33-88). Ten of the sarcomas were located in the lower extremity, 4 in the upper extremity, and 2 were located in the trunk. Four patients had metastatic disease at diagnosis. The majority of the patients received a total radiation dose of 30 Gy in 5 fractions (range, 27.5-40 Gy) on consecutive days. All patients were planned with intensity modulated radiation therapy or volumetric arc therapy. The median time to surgical resection after the completion of RT was 1 day (range, 0-7 days). The median time from initial biopsy results to completion of primary oncologic therapy was 20 days (range, 16-35). Ten patients achieved R0 resection, whereas the remaining 6 patients achieved R1 resection. Of the 13 patients assessed for local control, no patients developed local failure. Within the median follow-up time of 10.7 months (range, 1.7-33.2), 5 patients developed wound healing complications (31%), of which only 3 patients (19%) required return to the operating room.

      Conclusions

      Treatment of soft tissue sarcoma with preoperative hypofractionated RT followed by immediate resection resulted in a median of 20 days from biopsy results to completion of oncologic therapy. Early outcomes demonstrate favorable wound healing. Further prospective data with long-term follow-up is required to determine the oncologic outcomes and toxicity of hypofractionated preoperative RT.

      Introduction

      Soft tissue sarcomas are rare malignant tumors of mesenchymal origin. The mainstay of treatment is complete surgical resection and radiation therapy (RT), delivered either in the neoadjuvant or adjuvant setting. Local control and survival outcomes are similar when comparing neoadjuvant and adjuvant RT, though the toxicity profiles differ.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      ,
      • Davis A.M.
      • O'Sullivan B.
      • Turcotte R.
      • et al.
      Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma.
      Preoperative radiation therapy is known to have a higher rate of wound healing complications, but improved extremity function due to less fibrosis of the periarticular soft tissues.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      Conventional neoadjuvant RT regimens consist of 50 Gy in 25 fractions (fx) delivered over 5 weeks. When including a 3- to 6-week posttreatment period, time to surgical resection, and therefore completion of primary oncologic therapy, ranges between 8 to 11 weeks from the time RT is initiated.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      Hypofractionated RT, defined as >2.2 Gy delivered per fraction, has been shown to be efficacious in other cancer types, including breast,
      • Whelan T.J.
      • Pignol J.P.
      • Levine M.N.
      • et al.
      Long-term results of hypofractionated radiation therapy for breast cancer.
      • Haviland J.S.
      • Owen J.R.
      • Dewar J.A.
      • et al.
      The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials.
      • Livi L.
      • Meattini I.
      • Marrazzo L.
      • et al.
      Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial.
      rectal,
      • Erlandsson J.
      • Holm T.
      • Pettersson D.
      • et al.
      Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): A multicentre, randomised, non-blinded, phase 3, non-inferiority trial.
      and prostate cancer.
      • Lee W.R.
      • Dignam J.J.
      • Amin M.B.
      • et al.
      Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer.
      Prior experiences of preoperative hypofractionated regimens have used 3.5 to 8 Gy per fraction.
      • MacDermed D.M.
      • Miller L.L.
      • Peabody T.D.
      • et al.
      Primary tumor necrosis predicts distant control in locally advanced soft-tissue sarcomas after preoperative concurrent chemoradiotherapy.
      • Ryan C.W.
      • Montag A.G.
      • Hosenpud J.R.
      • et al.
      Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas.
      • Pennington J.D.
      • Eilber F.C.
      • Eilber F.R.
      • et al.
      Long-term outcomes with ifosfamide-based hypofractionated preoperative chemoradiotherapy for extremity soft tissue sarcomas.
      • Kubicek G.J.
      • LaCouture T.
      • Kaden M.
      • et al.
      Preoperative radiosurgery for soft tissue sarcoma.
      • Kosela-Paterczyk H.
      • Szacht M.
      • Morysinski T.
      • et al.
      Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.
      Hypofractionated regimens considerably shorten the entire treatment package time. This allows for quicker time receiving adjuvant therapies, undergoing physical therapy, and reintroduction of the patient back into society with less time off work. In 2014, Kosela-Paterczyk et al reported on a prospective single-arm study of 272 soft tissue sarcoma patients treated with 25 Gray in 5 fractions followed by immediate (within 3-7 days) surgical resection.
      • Kosela-Paterczyk H.
      • Szacht M.
      • Morysinski T.
      • et al.
      Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.
      Local control rate was lower than expected at 81% with a median follow-up of 35 months. However, the wound complication rate of 7% requiring reoperation was deemed favorable. Kalbasi et al reported on a single arm prospective study of patients with soft tissue sarcoma treated with 30 Gy in 5 fractions followed by delayed surgery (within 2-6 weeks).
      • Kalbasi A.
      • Kamrava M.
      • Chu F.-I.
      • et al.
      A phase II trial of 5-day neoadjuvant radiotherapy for patients with high-risk primary soft tissue sarcoma.
      The local control rates reported on 35 evaluable patients was 94.3% at 2 years. In this study, major wound complications occurred in 32%. At our institution, we have selectively used a high-dose preoperative hypofractionated regimen for patients with soft tissue sarcomas outside the abdomen and pelvis followed by immediate surgery. This represents a further advance combining the novel regimens previously published by Kosela-Paterczyk et al and Kalbasi et al.
      • Kosela-Paterczyk H.
      • Szacht M.
      • Morysinski T.
      • et al.
      Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.
      ,
      • Kalbasi A.
      • Kamrava M.
      • Chu F.-I.
      • et al.
      A phase II trial of 5-day neoadjuvant radiotherapy for patients with high-risk primary soft tissue sarcoma.
      Given the paucity of data (summarized in Table 1), we aimed to assess our early clinical, toxicity and histologic data of patients receiving hypofractionated RT followed by immediate surgical resection.

      Methods and Materials

      An institutional review board–approved database of patients treated with preoperative 5-fraction radiation regimens between 2016 and 2019 was queried. Patients with soft tissue sarcomas of the extremities or trunk treated with preoperative hypofractionated radiation therapy were included, whereas retroperitoneal sarcomas were excluded. The decision to use hypofractionated dosing regimen with immediate surgery was made as part of a multidisciplinary discussion and sarcoma tumor board. Patients with metastatic disease with long natural histories of disease, justifying aggressive local control or those with symptomatic primary tumors requiring local control and quick resumption of systemic therapy, were treated with short course radiation followed by immediate surgical resection. Patients with nonmetastatic disease were counseled regarding the current standard of care for preoperative long-course radiation therapy with conventional fractionation and delay to surgery. Patients consented to short course radiation therapy for various personal and logistical reasons. One patient treated with short course radiation therapy was an inmate at maximum security prison in a different city, who would not otherwise be able to receive preoperative radiation therapy. All patients were treated at a single institution. After surgical resection, patients were seen for surveillance every 3 to 6 months for the first 3 years. Surveillance imaging included a computed tomography (CT) chest without contrast and imaging of the primary tumor with magnetic resonance imaging (MRI).

      Network NCC. Soft tissue sarcoma (version 4.2019). Available at: https://www.nccn.org/. Accessed July 23, 2020.

      Radiation target delineation and treatment planning

      All patients received hypofractionated preoperative radiation therapy over 5 fractions. Tumor volumes were generally designed as was done on RTOG 0630.
      • Wang D.
      • Zhang Q.
      • Eisenberg B.L.
      • et al.
      Significant reduction of late toxicities in patients with extremity sarcoma treated with image-guided radiation therapy to a reduced target volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.
      The planning CT was registered with preoperative MRI imaging performed before or at the time of simulation. The gross tumor volume was defined based on preoperative MRI with sequence based on histology. The CTV was drawn to respect anatomic barriers to tumor spread. The planning target volume was generated by adding 5 mm to the CTV. Daily image guidance with cone beam computed tomography was used. Both step and shoot intensity modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT) radiation techniques were allowed. We attempted to limit bone in proximity to planning target volume to V15 Gy <50% and to spare a strip of skin >2 cm to less than 10 Gy. We also consulted with our orthopedic surgeons to avoid hotspots in the skin where the surgical wound was planned. Acute and late radiation-related toxicities as were graded per the Common Terminology Criteria for Adverse Events v4.0 toxicity criteria.

      Surgery and reconstruction

      Surgical resection was performed by an orthopedic oncologic surgeon (L.N. and N.M.), 0 to 7 days after completion of the preoperative RT. Timing decisions were based upon patient preference and surgeon schedules. Wound healing complications were defined as previously described by O’Sullivan et al.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      Major wound complications were those requiring return to the operating room, admission for intravenous antibiotics and wound packing >120 days, or aspiration of seroma.

      Statistical analysis and definitions

      Descriptive statistics were used to describe local failure, survival, toxicities, and wound complications of treatment. Local failure was assessed radiographically on surveillance MRI. Local failure was reported for patients who had >3 months of radiographic follow-up.

      Results

      Patient, tumor, and treatment characteristics

      A total of 16 patients met the study eligibility criteria. A summary of the patient, tumor, and treatment characteristics is included in Table 2. Ten patients had diagnoses of soft tissue sarcomas of the upper extremity, 4 lower extremity, and the remaining 2 patients had trunk sarcomas. The majority of the patients had localized disease; however 4 patients had metastatic disease at diagnosis. Of the 4 patients who had metastatic disease at diagnosis, 1 patient received chemotherapy within a short interval before preoperative radiation therapy and surgical resection and 1 patient received chemotherapy within a short interval after radiation therapy and surgical resection. The details of these 4 patients with metastatic disease can be found in the Supplementary Patient Data. Chemotherapy was not administered neoadjuvantly or adjuvant in nonmetastatic patients. Most patients received 30 Gy in 5 fractions, with a dose range of 27.5 Gy to 40 Gy. The median time from completion of radiation to surgical resection was 1 day (range, 0-7). Median time from initial biopsy results to completion of primary oncologic therapy was 20 days (range, 16-35) as shown in Figure 1. The median time from initial biopsy to completion of primary oncologic therapy was 27 days (range, 21-38).
      Table 1Summary of other studies employing hypofractionated preoperative radiation therapy for soft tissue sarcoma
      Author/institutionYearNo. of patientsDoseRadiation techniqueTime to surgeryPreoperative or concurrent chemotherapyLocal controlComplications requiring reoperation
      Ryan et al
      • Ryan C.W.
      • Montag A.G.
      • Hosenpud J.R.
      • et al.
      Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas.
      / Oregon Health and Science University
      20082528 Gy/ 8 fx3D conformal9 wkYes88% at 2 y20%
      MacDermed et al
      • MacDermed D.M.
      • Miller L.L.
      • Peabody T.D.
      • et al.
      Primary tumor necrosis predicts distant control in locally advanced soft-tissue sarcomas after preoperative concurrent chemoradiotherapy.
      / University of Chicago
      20103428 Gy/8 fx3D conformal4-8 wkYes89% at 5 y17.2%
      Kosela-Paterczyk et al
      • Kosela-Paterczyk H.
      • Szacht M.
      • Morysinski T.
      • et al.
      Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.
      / Maria Sklodowska Curie (Poland)
      201427225 Gy/5 fx3D conformal3-7 dYes81% at 3 y7%
      Pennington et al
      • Pennington J.D.
      • Eilber F.C.
      • Eilber F.R.
      • et al.
      Long-term outcomes with ifosfamide-based hypofractionated preoperative chemoradiotherapy for extremity soft tissue sarcomas.
      / University of California, Los Angeles
      201811628 Gy/8 fx3D conformal1-2 wkYes89% at 3 yNA
      Kubicek et al
      • Kubicek G.J.
      • LaCouture T.
      • Kaden M.
      • et al.
      Preoperative radiosurgery for soft tissue sarcoma.
      / Cooper University Hospital
      20181335 Gy-40 Gy/5 fx (every other d)Radiosurgery with CyberKnife4-8 wkOptional93% with median follow-up of 9.3 mo0%
      Kalbasi et al
      • Kalbasi A.
      • Kamrava M.
      • Chu F.-I.
      • et al.
      A phase II trial of 5-day neoadjuvant radiotherapy for patients with high-risk primary soft tissue sarcoma.
      /UCLA
      20205230 Gy/5 fxIMRT (76%), 3D conformal (20%), or electrons (4%)2-6 wkNone94% at 2 y32%
      Abbreviations: 3D = 3-dimensional; fx = number of fractions; IMRT = intensity modulated radiation therapy; UCLA = University of California, Los Angeles.
      The present study treated 16 patients with a mean dose of 30 Gy/5 fx on consecutive days followed by immediate surgical resection (within 7 days). All patients were treated with IMRT/volumetric arc therapy. Only patients with upfront metastatic disease were treated with preoperative chemotherapy. No local failures were observed within the follow-up time of 10.7 months. Complications requiring reoperation occurred in 19%.
      Table 2Patient, tumor, and treatment characteristics
      AgeMedian 64 y, (range, 33-88)
      Male9
      Female7
      Site
       Extremity14
       Upper extremity4
       Lower extremity10
       Trunk2
      Histology
       Dedifferentiated liposarcoma1
       CIC-rearranged sarcoma1
       Extraskeletal myxoid chondrosarcoma1
       Myxofibrosarcoma4
       Myxoid liposarcoma3
       Pleomorphic leiomyosarcoma1
       Synovial sarcoma2
       Undifferentiated pleomorphic/spindle cell sarcoma3
      Grade
      Grade not available for 5 patients.
       Grade 28
       Grade 33
      Greatest tumor dimension on final pathology
       ≤5 cm3
       >5 cm and ≤10 cm9
       >10 cm and ≤15 cm3
       >15 cm1
      Metastatic at diagnosis4
      PTV sizeMedian 485 cm3 (range, 56-4353)
      Radiation technique
       Step and shoot IMRT3
       VMAT16
      Radiation dose
       27.5 Gy/5 fx1
       30 Gy/5 fx14
       40 Gy/5 fx1
      Prior unplanned excision with longitudinal incision4
      Wound closure
       Primary closure13
       Regional/pedicled flap2
      One patient underwent closure with a regional pedicle flap and a skin graft.
       Free flap1
       Skin graft1
      One patient underwent closure with a regional pedicle flap and a skin graft.
      Incisional wound vacuum use with surgery13
      Pathologic margin status
       R010
       R16
       R20
      Abbreviations: fx = number of fractions; IMRT = intensity modulated radiation therapy; R0 = gross total resection; R1 = microscopically positive margins; R2 = macroscopically positive margins; volumetric arc therapy; VMAT = volumetric arc therapy.
      Grade not available for 5 patients.
      One patient underwent closure with a regional pedicle flap and a skin graft.
      Figure thumbnail gr1
      Figure 1Treatment schema for preoperative hypofractionated radiation therapy followed by immediate surgical resection. The median time from initial biopsy results to surgical resection was 20 days. Surgical resection occurred within 7 days of completion of radiation therapy. Abbreviation: SBRT = stereotactic body radiation therapy.

      Oncologic outcomes

      The median follow-up time was 10.7 months (range, 1.7-32.0). Within the follow-up time, 2 out of 16 patients died. Both of these patients had metastatic disease at the time of radiation and surgical resection, and continued to have distant progression, ultimately leading to demise. Within the follow-up time, no local failures were observed in the 13 patients with >3 months of radiologic follow-up. Gross total resections (R0) were achieved in 10 patients. In the remaining 6 patients, microscopically positive margins were identified. Five patients had planned marginal (R1) resections. One patient with myxofibrosarcoma had persistently positive margins outside of the radiation field after reresection. This patient underwent postoperative reirradiation conventional fractionation to 66 Gy in 33 fractions.

      Wound complications and toxicity

      No acute or late grade 3 or higher radiation-related toxicities were observed, including lymphedema, fibrosis, joint stiffness, skin hyperpigmentation, atrophy, or pain. Major wound complications requiring reoperation occurred in 3 out of 16 patients (18.8%). Minor wound complications occurred in 2 out of 16 patients (12.5%). Major and minor wound complications included dehiscense, skin necrosis, and seroma. Figure 2 demonstrates representative images of wound complications.
      Figure thumbnail gr2
      Figure 2Minor wound complication. This patient with skin necrosis, which ultimately led to cellulitis requiring short-term intravenous antibiotics, was characterized as a minor complication. This patient did not require reoperation.

      Discussion

      We present early oncologic and toxicity outcomes of treating soft tissue sarcomas with a 5-fraction preoperative hypofractionated radiation therapy courses followed by immediate surgical resection. This strategy significantly reduces the overall treatment time compared with conventional preoperative radiation therapy followed by delayed surgery, which generally ranges between 8 to 12 weeks. Our data demonstrate the median time from obtaining the biopsy results to surgical resection of the primary tumor, including preoperative radiation, was less than 3 weeks. In this way, the treatment package time was reduced by 5 to 9 weeks. This allows patients less absences from work and quicker resumption of activities of daily living. Additionally, for metastatic patients shortening the treatment course allows quicker resumption of systemic therapy.
      With only 3 of 16 patients requiring reoperation for wound healing complications, our data demonstrate a rate comparable to that reported in the literature for standard fractionation radiation therapy.
      • Karthik N.
      • Ward M.C.
      • Juloori A.
      • Scott J.
      • Mesko N.
      • Shah C.
      Factors associated with acute and chronic wound complications in patients with soft tissue sarcoma with long-term follow-up.
      In the National Cancer Institute of Canada study reported by O’Sullivan et al, acute wound complications were recorded in 35% of patients who received preoperative radiation therapy versus 17% in those that received postoperative radiation therapy. Of the patients who underwent preoperative radiation therapy, 16% of patients required reoperation owing to treatment complications.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      This is comparable to our series, in which nearly 19% of patients required a reoperation. To date, most preoperative short course radiation therapy series have used 3-dimensional conformal techniques over more modern techniques. Older 3-dimensional conformal techniques, as were used in the original National Cancer Institute of Canada study of preoperative versus postoperative therapy, demanded larger target volumes without dose painting to avoid normal structures.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      In our series, we uniquely used either step and shoot IMRT or volumetric arc therapy with image guidance for all patients. O’Sullivan et al demonstrated the use of IMRT with image guidance and that restricting radiation dose to future surgical skin flaps and bone reduced the risk of toxicity.
      • O'Sullivan B.
      • Griffin A.M.
      • Dickie C.I.
      • et al.
      Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma.
      Wang et al (RTOG 0630) further used image guidance to reduce target volumes, which led to decreased late toxicities without an increase in the risk of recurrence.
      • Wang D.
      • Zhang Q.
      • Eisenberg B.L.
      • et al.
      Significant reduction of late toxicities in patients with extremity sarcoma treated with image-guided radiation therapy to a reduced target volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.
      The radiation techniques used in this study were modeled after RTOG 0630. Surgical efforts to decrease wound healing complications in this study included immediate surgical resection, layered closure when possible, use of deep drains to prevent seroma formation, and standard use of incisional wound negative pressure therapy techniques. No patients received concurrent chemotherapy with radiation therapy, and only 2 patients received chemotherapy within a short interval of radiation therapy (one patient received doxorubicin/temsirolimus 1 week before radiation, and 1 patient received gemcitabine/docetaxel 6 weeks after surgical resection). Therefore, the effects of chemotherapy on wound complications cannot be ascertained in this study.
      Local control in this study is favorable, although our follow-up interval is too short to make definitive statements. There were no local failures observed within the follow-up period. Maturation of data are important to ensure longer term control remains favorable. A recent study of hypofractionated preoperative radiation (30 Gy in 5 fractions) followed by surgical resection within 2 to 6 weeks reported by Kalbasi et al demonstrated a 2-year local control rate of 94.3%.
      • MacDermed D.M.
      • Miller L.L.
      • Peabody T.D.
      • et al.
      Primary tumor necrosis predicts distant control in locally advanced soft-tissue sarcomas after preoperative concurrent chemoradiotherapy.
      This can be compared with the historical standard 5-year local control of 93%.
      • O'Sullivan B.
      • Davis A.M.
      • Turcotte R.
      • et al.
      Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial.
      Table 2 summarizes the local control rates for prior experiences with hypofractionated preoperative radiation therapy. The largest reported series to date demonstrated an unexpectedly low 3-year local control rate of 81%.
      • Kosela-Paterczyk H.
      • Szacht M.
      • Morysinski T.
      • et al.
      Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.
      This may be attributed to a low total radiation dose of 25 Gy in 5 fractions without chemotherapy. We chose to treat all patients with doses greater than 25 Gy (EQD2 = 40, calculated at alpha-beta ratio of 3) owing to the lower local control observed in that report. Most patients received radiation doses of 30 Gy in 5 fractions (EQD2 = 54, calculated at alpha-beta ratio of 3) before surgery with favorable toxicity profiles. In our series, immediate surgical resection was used in an effort to shorten the overall treatment course, similar to the treatment regimen published by Kosela-Paterczyk et al.
      • Kosela-Paterczyk H.
      • Szacht M.
      • Morysinski T.
      • et al.
      Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.
      New approaches in oncology are evaluated not only based on outcomes but value. Traditionally, preoperative radiation therapy consists of 25 fractions of radiation and postoperatively 30 to 33 fractions. A 5 fraction IMRT approach would provide great value compared with a 25 or 30 to 33 fractions of radiation delivered with IMRT. Data have demonstrated that 5 fractions of IMRT is reimbursed less than 15 fractions of 3-dimensional CRT so even if standard preoperative or postoperative radiation was delivered with 3-dimensional CRT compared with IMRT, a cost savings would be realized.
      • Shah C.
      • Ward M.C.
      • Tendulkar R.D.
      • Cherian S.
      • Vicini F.
      • Singer M.E.
      Cost and cost-effectiveness of image guided partial breast irradiation in comparison to hypofractionated whole breast irradiation.
      Finally, indirect costs that patients cover including missed work, travel and childcare are reduced with a shorter course of radiation therapy.
      As a retrospective study design, this investigation has inherent limitations. The primary limitation is a selection bias of patients who have tumors felt to be amenable to hypofractionated radiation therapy and excluded cases at high-risk for toxicity (such as circumferential tumor close to bone). Longer follow-up and a larger cohort of patients is necessary to accurately determine the risk of severe wound complications, which may be underestimated in this study. The short follow-up in this study may underestimate late toxicities such as lymphedema and soft tissue fibrosis which may have not yet manifested. Additional limitations include a small number of patients as well a heterogeneous group to stage, histology, location, and range of RT doses. Further prospective studies are required employing modern techniques of preoperative hypofractionated radiation therapy and immediate surgical resection.

      Conclusions

      Our use of hypofractionated preoperative RT for soft tissue sarcoma with immediate resection resulted in a median of 20 days from biopsy results to resection of the primary tumor, reducing the time from diagnosis to completion of primary oncologic therapy by nearly 3 months for these patients. Early outcomes demonstrate an acceptable rate of wound healing complications comparable to standard therapy. Further prospective data with long-term follow-up is required to determine the oncologic outcomes and toxicity of preoperative hypofractionated RT.

      Acknowledgments

      We thank the following specialists who helped us to care for the patients in the study: nurses, therapists, dosimetrists, and physicists.

      Supplementary data

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