Myxofibrosarcoma: Outcomes, Prognostic Factors, and Role of Neoadjuvant Radiation Therapy.

Purpose: Myxofibrosarcoma (MFS) is a subtype of soft tissue sarcoma with a highly infiltrative growth pattern that leads to a higher risk of inadvertent positive surgical margins and local relapse. Poorly defined tumor margins also pose a challenge for radiation therapy (RT) planning, in terms of treatment volumes and administration of pre- versus postoperative RT. This study aims to evaluate local control and patterns of recurrence in patients with MFS treated with neoadjuvant RT followed by definitive surgical excision. Methods and Materials: Multiple institutional databases were retrospectively searched for patients diagnosed with MFS between 2013 and 2021 who were exclusively treated with preoperative RT followed by definitive surgery at our institution. The endpoints of the study were defined as local tumor recurrence, distant metastasis, and death after the date of definitive surgery. Results: Forty-nine patients met the inclusion criteria and were included in the final study. The median age at diagnosis was 67 years, and 71% of patients were male. The tumor was superficially located in 63% of patients, and the mean tumor size at presentation was 7.8 cm. All patients received neoadjuvant RT and completed their planned course of treatment. Neoadjuvant chemotherapy was administered in 22% of patients. Inadvertent excision (IE) before definitive treatment was performed in 25 patients (51%), 84% of which had superficially located tumors. All margins were assessed using frozen section analysis at the time of definitive surgery, and 100% of patients had negative surgical margins, with 25% having no residual tumor. With a median follow-up of 4.7 years, the 5-year local control rate was 87%, and 5-year overall survival was 98%. Tumor depth was associated with distant metastasis (P < .01). Conclusions: Despite the infiltrative nature of MFS, preoperative RT followed by definitive surgical excision, especially in the setting of a reliable frozen section margin analysis, was associated with excellent local control.

Spatially Fractionated Radiation Therapy in Sarcomas: A Large Single-Institution Experience.

Purpose: Spatially fractionated radiation therapy (SFRT) is a recognized technique for enhancing tumor response in radioresistant and bulky tumors. We analyzed clinical and treatment outcomes in patients with bone and soft tissue sarcomas treated with modern SFRT techniques. Methods and Materials: Patients with metastatic or unresectable sarcoma treated with brass collimator, volumetric modulated arc therapy lattice, or proton SFRT from December 2019 to June 2022 were retrospectively reviewed. Consolidative external beam radiation therapy (EBRT) was delivered at the physician's discretion. Patient and treatment characteristics, treatment response (symptom improvement, local control, and imaging response), and toxicity data were collected. Results: The cohort consisted of 53 patients treated with 61 SFRT treatments. Median age at treatment was 60.0 years. The primary location was soft tissue in 46 courses (75%) and bone in 15 (25%). Fifty-three courses (87%) were treated for symptom relief. The most used SFRT technique was volumetric modulated arc therapy lattice (n = 52, 85%) to a dose of 20 Gy (n = 48, 79%; range, 16-20 Gy). EBRT was delivered post-SFRT in 55 (90%) treatment courses with a median time interval from SFRT to EBRT of 5 days (range, 0-14 days). Median physical EBRT dose and fractionation was 40 Gy (range, 9-73.5 Gy) and 10 fractions (range, 3-33 fractions). Median follow up was 7.4 months (range, 0.2-30 months). One-year overall survival and local control rates were 53% and 82%. Symptom relief was documented with 32 treatment courses (60%). Stable or partial response was observed with 47 treatment courses (90%). Four grade 3 to 4 acute and subacute toxicities were attributable to SFRT (8%). Conclusions: The current series is the largest to date documenting outcomes for SFRT in sarcomas. Our results suggest combined SFRT with EBRT is associated with a favorable toxicity profile and high rates of symptomatic and radiographic responses for metastatic or unresectable sarcomas.

Automated target placement for VMAT lattice radiation therapy: enhancing efficiency and consistency.

Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.

Central subfield thickness predicts visual acuity outcomes in plaque-irradiated eyes with choroidal melanoma.

OBJECTIVE: To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement. DESIGN: Single-center retrospective study. PARTICIPANTS: Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated. RESULTS: Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 µm (median 14.0, range - 60.0-182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch's membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02-1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01-1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections. CONCLUSION: Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy.

Clinical aspects of spatially fractionated radiation therapy treatments.

PURPOSE: To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach. METHODS: We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions. RESULTS: SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists. CONCLUSIONS: We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use.

Prognostic factors in patients with endometrial cancer with isolated lymphatic recurrence.

OBJECTIVE: To analyze the clinicopathological features and outcomes in patients with endometrial cancer with isolated lymphatic recurrence after lymphadenectomy, stratified by different isolated lymphatic recurrence sites and treatment approaches. METHODS: We retrospectively reviewed all surgically treated patients with endometrial cancer, identifying those with recurrence. We defined primary isolated lymphatic recurrence as the first and unique evidence of recurrence in lymph node-bearing areas, without concomitant vaginal, hematogenous, or peritoneal recurrence. Isolated lymphatic recurrences were classified as pelvic, para-aortic, distant, or multiple sites. Our primary outcome was cause-specific survival after diagnosis of the recurrence. RESULTS: Among 4216 patients with surgically staged endometrial cancer, we identified 66 (1.6%) women with isolated lymphatic recurrence. The overall median cause-specific survival for patients with isolated lymphatic recurrence was 24 months. Although cause-specific survival was not significantly different between the four isolated lymphatic recurrence groups (p=0.21), 7 of 15 (47%) patients with isolated lymphatic recurrence in the para-aortic area were long-term survivors. At multivariate Cox regression, the absence of lymphovascular space invasion and grade 1 histology in the primary tumor were significantly associated with improved cause-specific survival. In addition, patients with isolated lymphatic recurrence who underwent surgery for recurrence (with/without other associated therapies) had improved cause-specific survival compared with patients who did not undergo surgery, also after adjusting for age. CONCLUSIONS: Low-grade histology and absence of lymphovascular space invasion in the primary tumor were predictors of improved prognosis in patients with endometrial cancer with isolated lymphatic recurrence. In addition, in this retrospective cohort, patients with isolated lymphatic recurrence who were selected for eradicative surgical treatment had improved cause-specific survival.

Dosimetric comparison between proton beam therapy, intensity modulated radiation therapy, and 3D conformal therapy for soft tissue extremity sarcoma.

PURPOSE/OBJECTIVES: Proton beam therapy (PBT) may provide a dosimetric advantage in sparing soft tissue and bone for selected patients with extremity soft sarcoma (eSTS). We compared PBT with photons plans generated using intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS/METHODS: Seventeen patients previously treated with pencil beam scanning PBT were included in this study. Of these patients, 14 treated with pre-operative 50 Gy in 25 fractions were analyzed. IMRT and 3D-CRT plans were created to compare against the original PBT plans. Dose-volume histogram (DVH) indices were evaluated amongst PBT, IMRT, and 3D plans. Kruskal-Wallis rank sum tests were used to get the statistical significance. A p value smaller than .05 was considered to be statistically significant. RESULTS: For the clinical target volume (CTV), D2%, D95%, D98%, Dmin, Dmax, and V50Gy, were assessed. Dmin, D1%, Dmax, Dmean, V1Gy, V5Gy, and V50Gy were evaluated for the adjacent soft tissue. D1%, Dmax, Dmean, and V35-50% were evaluated for bone. All plans met CTV target coverage. The PBT plans delivered less dose to soft tissue and bone. The mean dose to the soft tissue was 2 Gy, 11 Gy, and 13 Gy for PBT, IMRT, and 3D, respectively (p < .001). The mean dose to adjacent bone was 15 Gy, 26 Gy, and 28 Gy for PBT, IMRT, and 3D, respectively (p = .022). CONCLUSION: PBT plans for selected patients with eSTS demonstrated improved sparing of circumferential soft tissue and adjacent bone compared to IMRT and 3D-CRT. Further evaluation will determine if this improved dosimetry correlates with reduced toxicity and improved quality of life.

Trimodality Therapy Improves Disease Control in Radiation-Associated Angiosarcoma of the Breast.

PURPOSE: To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. EXPERIMENTAL DESIGN: With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. RESULTS: A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P < 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3-44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. CONCLUSIONS: Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.

Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy.

PURPOSE: Secondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized. METHODS AND MATERIALS: We reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI. RESULTS: A 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy. CONCLUSIONS: Our case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.

Treatment outcomes of extraskeletal Ewing sarcoma.

PURPOSE: Extraskeletal Ewing sarcoma (EES), is a rare soft tissue sarcoma. Treatment for EES commonly involves chemotherapy and surgical resection (ST) or less commonly combined chemotherapy, surgery, and radiotherapy (ST + RT). The purpose of the current study was to evaluate our institutional experience treating EES. METHODS: We reviewed 36 (18 males:18 females) patients (mean age 30 years) with a nonretroperitoneal/visceral EES treated with either ST (n = 24, 67%) or ST + RT (n = 12, 33%). All patients were treated with chemotherapy, most commonly vincristine, doxorubicin, cyclophosphamide/ifosfamide and etoposide (VDC/IE, n = 23, 66%) Radiotherapy was mostly delivered preoperatively (n = 9). The mean follow-up was 8 years. RESULTS: The 10-year disease specific survival for patients was 78%, with no difference in the survival between patients in the ST versus the ST + RT groups (83% vs. 71%, p = 0.86). There was no difference in the 10-year local recurrence (91% vs. 100%, p = 0.29) or metastatic free survival (87% vs. 75%, p = 0.45) between the ST and ST + RT groups. CONCLUSION: The results of the current study highlight the ability to achieve excellent local control with chemotherapy and surgery for EES. We recommend for multidisciplinary management of patients with EES, including chemotherapy and surgery, with use of radiotherapy if there is concern for a potentially close margin of resection.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Outcomes of Proton Beam Therapy Compared With Intensity-Modulated Radiation Therapy for Uterine Cancer.

Purpose: To compare Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in patients with endometrial cancer receiving adjuvant pelvic radiation therapy with proton beam therapy (PT) versus intensity-modulated radiation therapy (IMRT). Materials and Methods: Patients with uterine cancer treated with curative intent who received either adjuvant PT or IMRT between 2014 and 2020 were identified. Patients were enrolled into a prospective registry using a gynecologic-specific subset of PRO-CTCAE designed to assess symptom impact on daily living. Questions included gastrointestinal (GI) symptoms of diarrhea, flatulence, bowel incontinence, and constipation in addition to other pertinent gynecologic, urinary, and other general symptoms. Symptom-based questions were on a 0- to 4-point scale, with grade 3+ symptoms occurring frequently or almost always. Patient-reported toxicity was analyzed at baseline, end of treatment (EOT), and at 3, 6, 9, and 12 months after treatment. Unequal variance t tests were used to determine if treatment type was a significant factor in baseline-adjusted PRO-CTCAE. Results: Sixty-seven patients met inclusion criteria. Twenty-two received PT and 45 patients received IMRT. Brachytherapy boost was delivered in 73% of patients. Median external beam dose was 45 Gy for both PT and IMRT (range, 45-58.8 Gy). When comparing PRO-CTCAE, PT was associated with less diarrhea at EOT (P = .01) and at 12 months (P = .24) than IMRT. Loss of bowel control at 12 months was more common in patients receiving IMRT (P = .15). Any patient reporting grade 3+ GI toxicity was noted more frequently with IMRT (31% versus 9%, P = .09). Discussion: Adjuvant PT is a promising treatment for patients with uterine cancer and may reduce patient-reported GI toxicity as compared with IMRT.

Lack of radiosensitivity predicts poor disease specific survival in myxoid liposarcoma.

BACKGROUND: Compared to other sarcomas, myxoid liposarcoma (ML) is known to be radiosensitive, with improved oncologic outcomes. Although these tumors "shrink" following radiotherapy, there is a paucity of data examining the degree of radiosensitivity and oncologic outcome. The purpose of the study was to evaluate pre- and postradiotherapy tumor volume to determine if size reduction impacts outcome. METHODS: We reviewed 62 patients with ML undergoing surgical resection combined with preoperative radiotherapy, with pre- and postradiotherapy MRI. This included 34 (55%) males, with a mean age of 47 ± 14 years. All tumors were deep to the fascia, and 12 (19%) patients had tumors with a >5% round-cell component. RESULTS: The mean volume reduction was 54% ± 29%. Compared to patients with >25% volume reduction, patients with reduction ≤25% had worse 10-year disease specific survival (86% vs. 37%, p < 0.01), in addition to an increased risk of metastatic disease (HR 4.63, p < 0.01) and death due to disease (HR 4.52, p < 0.01). CONCLUSION: Lack of volume reduction is a risk factor for metastatic disease and subsequent death due to disease in patients with extremity ML treated with combined preoperative radiotherapy and surgery. This data could be used to stratify patients for adjuvant therapies and follow-up intervals.

NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer.

OBJECTIVE: To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). METHODS: We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. RESULTS: Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

High Positive Predictive Value of Multitarget Stool DNA After Aerodigestive Tract Radiotherapy.

BACKGROUND AND AIMS: Multitarget stool DNA (mt-sDNA) is approved for average-risk colorectal cancer screening; test performance in persons with prior radiation therapy (RT) has not been studied. RT can induce gastrointestinal bleeding and alter DNA methylation, which may affect mt-sDNA accuracy. Among patients previously treated with RT, we aimed to measure the positive predictive value (PPV) of mt-sDNA and compare these results to historical estimates of mt-sDNA PPV among average-risk patients. METHODS: After institutional review board approval, we conducted a retrospective cohort study of a multisite academic and community-based practice. Patients with RT and subsequent mt-sDNA use during the study period (2014-2016) were identified. The findings at diagnostic colonoscopy were compared with published reports among average-risk patients. Nominal P values were generated by 2-tailed Fisher's exact testing in comparisons of colorectal neoplasia (CRN) rates between groups. RESULTS: There were 220 patients who had RT before mt-sDNA testing. RT was delivered along the aerodigestive tract in 108 patients. Mt-sDNA tests were positive in 45 of 220 patients (20%), and colonoscopy findings were available for 42; 31 of 42 patients (74%) had CRN. PPV by mt-sDNA was similar when stratified by site of prior RT (along vs outside the aerodigestive tract; P = 1.00). Detection of advanced CRN (36%) was nominally higher than previously published retrospective (27%) and prospective (20%) studies. The median time from the start of RT to mt-sDNA use was 7 (interquartile range, 3-14) years. CONCLUSION: With a test positivity rate and PPV for CRN similar to reports among average-risk patients, prior RT does not appear to adversely affect mt-sDNA performance.

Early Experience Using Proton Beam Therapy for Extremity Soft Tissue Sarcoma: A Multicenter Study.

Purpose: Proton beam therapy (PBT) may provide an advantage when planning well-selected patients with extremity soft tissue sarcoma (eSTS), specifically for large, anatomically challenging cases. We analyzed our early experience with PBT on toxicity and outcomes. Materials and Methods: A retrospective study was performed for eSTS treated between June 2016 and October 2020 with pencil beam scanning PBT at 2 institutions. Diagnostic, treatment, and toxicity characteristics were gathered from baseline to last follow-up or death. Wound complications were defined as secondary operations for wound repair (debridement, drainage, skin graft, and muscle flap) or nonoperative management requiring hospitalization. Statistical analysis was performed with R software. Results: Twenty consecutive patients with a median age 51.5 years (range, 19-78 years) were included. Median follow-up was 13.7 months (range, 1.7-48.1 months). Tumor presentation was primary (n = 17) or recurrent after prior combined modality therapy (n = 3). Tumor location was either lower extremity (n = 16) or upper extremity (n = 4). Radiation was delivered preoperatively in most patients (n = 18). Median pretreatment tumor size was 7.9 cm (range, 1.3 -30.0 cm). The 1-year locoregional control was 100%. Four patients (20%) had developed metastatic disease by end of follow-up. Maximum toxicity for acute dermatitis was grade 2 in 8 patients (40%) and grade 3 in 3 patients (15%). After preoperative radiation and surgical resection, acute wound complications occurred in 6 patients (35%). Tumor size was larger in patients with acute wound complications compared with those without (medians 16 cm, range [12-30.0 cm] vs 6.3 cm, [1.3-14.4 cm], P = .003). Conclusion: PBT for well selected eSTS cases demonstrated excellent local control and similar acute wound complication rate comparable to historic controls. Long-term follow-up and further dosimetric analyses will provide further insight into potential advantages of PBT in this patient population.

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

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

A Dosimetric Comparison of Lattice, Brass, and Proton Grid Therapy Treatment Plans.

PURPOSE: Our purpose was to dosimetrically compare volumetric modulated arc therapy (VMAT) lattice radiation therapy (LRT), brass, and proton grid therapy planning techniques and suggest potential clinical applications for each. METHODS AND MATERIALS: Four plans delivering 20 Gy in 1 fraction were created for each of 22 patients. Brass and proton grid plans used a single static field and the same beam angle. Proton grid plans used the same beam size and spacing as the brass block. Two VMAT LRT plans were generated for each patient: one with 1-cm diameter lattice points spaced 2-cm center-to-center (2-cm VMAT) and another with 1.5-cm diameter lattice points spaced 3-cm center-to-center (3- cm VMAT). Maximum, minimum, mean, and equivalent uniform dose and the dose to 90%, 50%, 20%, 10%, and 5% (D90%[%], D50%[%], etc) of gross tumor volume (GTV) were reported. D10%/D90% characterized dose heterogeneity. Normal tissue dose was generalized by the maximum dose and volume in cubic centimeters of tissue outside the GTV receiving 30% and 50% of prescription (body-GTV V30%[cm3]; body-GTV V50%[cm3]). RESULTS: VMAT LRT plans delivered the highest maximum GTV doses while brass and proton plans delivered higher D5%(%), D10%(%), and D20%(%) values. D50%(%), D90%(%), and minimum dose varied little between plan types. Proton and brass plans had the highest dose heterogeneity. Two-centimeter VMAT and brass grid plans had the highest mean GTV doses. Two-centimeter VMAT plans had the highest equivalent uniform dose, followed by 3-cm VMAT, brass, and proton plans. VMAT LRT plans exhibited the lowest normal tissue maximum and body GTV V30%(cm3) and body GTV V50%(cm3) values. CONCLUSIONS: An in-depth comparison of target and normal tissue dosimetric parameters for common photon and proton grid therapy planning techniques was made. Strengths of each plan type were noted leading to general recommendations on usage.

Preoperative Radiation for Soft Tissue Sarcomas: How Much Is Needed?

OPINION STATEMENT: Preoperative radiation therapy is an important component of curative treatment for extremity and superficial trunk soft tissue sarcomas. It has traditionally been delivered to a dose of 50 Gy in 2 Gy fractions over 5 weeks. With significant advances in the multidisciplinary approach to soft tissue sarcomas, preoperative radiation therapy may be omitted for certain cases, delivered over a shortened period of time (1-3 weeks), deintensified for myxoid liposarcomas, or combined with systemic therapy to improve the therapeutic ratio. This article reviews the innovative preoperative radiation therapy strategies currently used to treat extremity and superficial trunk soft tissue sarcomas.