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Radiation therapy is an integral component of local management with oncologic resection for soft tissue sarcoma. Radiotherapy is indicated in patients at an increased risk of local recurrence so that improved local control may be achieved. Sequencing of radiotherapy and resection should be determined by multidisciplinary input before treatment initiation. For most patients, preoperative delivery of radiation therapy is preferred. In patients initially thought to be at low risk for local recurrence and found to have unexpected adverse pathologic features at resection, postoperative radiation therapy is indicated. The use of radiation therapy for retroperitoneal sarcoma is controversial; when used, preoperative delivery of radiation is recommended.

PURPOSE/OBJECTIVE(S): This study describes the pattern of failure in patients with biochemical (BCR) recurrence after low-dose-rate (LDR) brachytherapy as a component of definitive treatment for prostate cancer. METHODS: Patients with BCR after LDR brachytherapy ± external beam radiation therapy (EBRT) were enrolled on prospective IRB approved advanced imaging protocols. Patients underwent 3T multiparametric MRI (mpMRI); a subset underwent prostate specific membrane antigen (PSMA)-based PET/CT. Pathologic confirmation was obtained unless contraindicated. RESULTS: Between January 2011 and April 2021, 51 patients with BCR after brachytherapy (n = 36) or brachytherapy + EBRT (n = 15) underwent mpMRI and were included in this analysis. Of 38 patients with available dosimetry, only two had D90 < 90%. The prostate and seminal vesicles were a site of failure in 66.7% (n = 34) and 39.2% (n = 20), respectively. PET/CT (n = 32 patients) more often identified lesions pelvic lymph nodes (50%; n = 16) and distant metastases (18.8%; n = 6), than mpMRI. Isolated nodal disease (9.8%; n = 5) and distant metastases (n = 1) without local recurrence were uncommon. Recurrence within the prostate was located in the transition zone in 48.5%, central or midline in 45.5%, and anterior in 36.4% of patients. CONCLUSION: In this cohort of patients with BCR after LDR brachytherapy ± EBRT, the predominant recurrence pattern was local (prostate ± seminal vesicles) with frequent occurrence in the anterior prostate and transition zone. mpMRI and PSMA PET/CT provided complementary information to localize sites of recurrence, with PSMA PET/CT often confirming mpMRI findings and identifying occult nodal or distant metastases. Published by Elsevier Inc. on behalf of American Brachytherapy Society.

Retroperitoneal sarcoma comprises a small subset of all soft tissue sarcoma and includes various histopathologic subtypes, each with unique patterns of behavior and differential risks for local recurrence and hematogenous metastatic spread. The primary treatment modality is surgery, although even with complete macroscopic resection, recurrence is common. The rationale for the addition of radiotherapy to resection is to improve local control; however, the use of radiation therapy for retroperitoneal sarcoma is controversial, and existing data are suboptimal to guide management. Treatment decisions should be determined with multidisciplinary input and shared decision-making. When used in selected patients, radiation therapy should be delivered preoperatively; postoperative treatment is not recommended.

Purpose This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults. Methods The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Results Multidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended. Conclusions Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life.

The goal of this article is to serve as a primer for the United States-based radiation oncologist who may be interested in learning more about radiopharmaceutical therapy (RPT). Specifically, we define RPT, review the data behind its current and anticipated indications, and discuss important regulatory considerations for incorporating it into clinical practice. RPT represents an opportunity for radiation oncologists to leverage 2 key areas of expertise, namely therapeutic radiation therapy and oncology, and apply them in a distinct context in collaboration with nuclear medicine and medical oncology colleagues. Although not every radiation oncologist will incorporate RPT into their day-to-day practice, it is important to understand the role for this modality and how it can be appropriately used in select patients.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts.

ImportancePathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).ObjectiveWe sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.Design, Setting, and ParticipantsRTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes.InterventionPatients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone.Main Outcomes and MeasuresOverall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017.ResultsOverall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45).Conclusions and RelevanceThis ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies.Trial RegistrationClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791)

In prone breast radiation, as the medial tangential beam usually passes through the immobilization board and couch, it is necessary to quantify the attenuation effect and the potential skin dose enhancement from these external structures. The prone breast board studied consists of an insert on which the contralateral breast rests and a board base indexed to the couch. Two different Varian couch systems were also studied. Transmission factors (TF) of the board were measured using a Farmer chamber at 4 cm depth. Couch TFs were measured using a thimble chamber centered in a cylindrical phantom. A custom support model was created in the treatment planning system (TPS). TFs were then computed in the TPS for comparison. Selected clinical plans were recomputed in the TPS incorporating external structures for target coverage evaluation. The correction for the attenuation effect in the TPS was also demonstrated. Skin dose effects were evaluated using a Markus parallel plate chamber with a 1 mm buildup cap. Measured insert TFs ranged 0.976 to 0.983 for 6 MV and 0.990 to 0.999 for 23 MV. Board base TFs ranged 0.979 to 0.985 for 6 MV and 0.989 to 0.998 for 23 MV. TPS values agreed within 0.9% and 0.5% for the insert and board base, respectively. Assigned Hounsfield units (HUs) providing the best agreement were 200, -100, and -900 for the insert, the board "base shell" and "base inside," respectively. Varian Exact Couch and Exact IGRT Couch TFs varied with respect to couch angle, with minimum values of 0.837 and 0.956, respectively, for 6 MV. The clinical treatment volume (CTV) and whole breast receiving 95% of the prescription dose (CTV-V95 and WB-V95) of selected patients demonstrated reduced coverage due to attenuation of external structures. Close proximity to the base increased skin dose by up to 25% to 30%. Contacting the insert increased skin dose by 65% to 93% for 6 MV and 117% to 157% for 23 MV, respectively. Results have shown reduced coverage by attenuating external structures. Proper modeling of immobilization devices and couch structures in the TPS should be implemented for accurate dose calculation. Increased surface doses were observed due to direct contact to the insert or close proximity to the base. Further study is required to quantify such a skin dose enhancement effect and its correlation to clinically apparent skin effects and toxicity.

Purpose Outcome data on hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2−) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+HER2− MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+HER2− MBC with prior exposure to everolimus while receiving palbociclib-based therapy. Patients and Methods A retrospective, single-institute review was conducted of HR+HER2− MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks. Results Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively. Conclusion There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings.

Purpose/Objective(s) Low dose rate (LDR) brachytherapy alone or with external beam radiation (EBRT) results in excellent rates of biochemical control in patients (pts) with prostate cancer (PCa). Understanding failure patterns in pts with biochemical recurrence (BCR) may inform implant technique or pt selection. The primary objective of this study was to describe locations of recurrence on multiparametric MRI (mpMRI) and prostate specific membrane antigen (PSMA) imaging in pts with BCR after LDR brachytherapy. Materials/Methods Pts with BCR after definitive LDR (± EBRT, ± androgen deprivation therapy (ADT)) referred for IRB approved imaging protocols were included. All pts underwent 3T mpMRI (T2 weighted, dynamic contrast-enhanced, and diffusion-weighted imaging) prospectively reviewed by prostate-dedicated radiologists. A subset of pts underwent PSMA-PET/CT imaging. Pathologic confirmation was obtained unless contraindicated. Prostate lesions were categorized as left (L)/right (R)/midline (ML); transitional zone (TZ)/peripheral zone (PZ); apical/mid/base; and anterior/posterior/central. Locations of recurrence (prostate, seminal vesicles (SV), lymph nodes (LN) and distant metastases (DM)) were recorded and reported descriptively. Results Between Jan 2011 and Feb 2021, 57 pts with BCR after LDR underwent prostate mpMRI. Treatment was LDR (n = 39) or EBRT + LDR (n = 18), ± ADT (n = 12). At time of LDR, initial Gleason score was ≤ 6 (n = 29), 7 (n = 19), 8-9 (n = 8), unknown (n = 1) and median PSA was 6 ng/mL (3.4-49). Of dosimetry available (n = 27), 2 had D90 Conclusion In this cohort of pts with BCR following LDR, the predominant locations of local recurrence were in the anterior/central TZ and SV. PSMA corroborated the majority of mpMRI findings and often demonstrated LN and DM. These findings may inform LDR technique and impact patient selection or pre-treatment imaging evaluation; and should be confirmed in larger subsets and correlated with post-implant dosimetry.

Radiation induced lung injury (RILI) encompasses radiation induced pneumonitis, inflammation of the lung which may manifest as a dose-limiting acute or sub-acute toxicity, and radiation induced lung fibrosis, a late effect of lung exposure to radiation. This review aims to highlight developments in molecular radiation biology of radiation induced lung injury and their implications in clinical practice

Background and purpose: Both multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen (PSMA)-targeting positron emission tomography (PET) imaging have shown promise in early localization of prostate cancer (PCa) recurrence after primary external beam radiotherapy. Detecting recurrence after brachytherapy for PCa using MRI is significantly hampered by susceptibility artifacts secondary to brachy seeds. Here, we compare the efficacy of 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET/CT versus mpMRI for detecting sites of local recurrence after low dose rate (LDR) brachytherapy for prostate cancer. Materials and methods: A total of 155 patients with a history of recurrent PCa who underwent mpMRI at 3 Tesla and 18F-DCFPyL PET/CT were retrospectively reviewed. Patients who underwent LDR brachytherapy for PCa and had subsequent biochemical recurrence (BCR) followed by mpMRI and 18F-DCFPyL PET/CT were included in this study. mpMRI was performed on a 3T scanner with endorectal and surface coils and images were prospectively read by a single expert radiologist. The 18F-DCFPyL PET/CT scan was prospectively interpreted by one of two nuclear medicine physicians. Patients underwent targeted biopsy when deemed clinically necessary and specimens were interpreted by an expert GU pathologist. Positivity rates (PR) from mpMRI and 18F-DCFPyL PET/CT were compared, and pathology results were used to calculate the positive predictive value (PPV) of each imaging modality for detecting PCa recurrence.Results: 14 patients who underwent LDR brachytherapy and had subsequent biochemical failure were imaged with mpMRI and 18F-DCFPyL PET/CT. 17 lesions were identified on at least one imaging modality. The PR for detection of intraprostatic lesions was 71% (10/14) for PET/CT and 64.3% (9/14) for mpMRI. 18F-DCFPyL PET/CT identified pelvic and extra-pelvic lymph nodes in 8 (57%) patients, while mpMRI noted positive lymph node findings in only 2 (14%) patients. A total of 14 lesions corresponding to 8 patients were targeted for biopsy and in these, 18F-DCFPyL PET/CT performed better than mpMRI for the detection of local recurrence with a PPV of 81.8% vs. 66.7%. For the detection of intraprostatic lesions, 18F-DCFPyL PET/CT and mpMRI had a PPV of 87.5% and 71.4%, respectively. Conclusion: Our findings suggest that 18F-DCFPyL PET/CT detects local and regional recurrent PCa after LDR brachytherapy at a higher rate than mpMRI and has a much higher detection rate of suspicious pelvic lymph nodes. Further studies are needed to validate these findings in larger cohorts.

PURPOSE/OBJECTIVE(S) Increasingly hypofractionated dose schedules for post prostatectomy radiotherapy to the prostate bed were investigated on a phase I trial. The final toxicity results for patients treated on Arm 2 (no visible recurrence on pelvic MRI) are reported here. The primary objective of this trial was to determine the maximal tolerated hypofractionated dose (MTHD) regimen. MATERIALS/METHODS Patients were treated on 1 of 3 dose levels (DL): 56.4 Gy in 20 fractions (DL1), 51.2 Gy in 15 fractions (DL2), and 44.2 Gy in 10 fractions (DL3). Patients underwent treatment to the prostate bed (RTOG Consensus); pelvic nodal irradiation was not allowed. Concurrent androgen deprivation therapy (ADT) was used at the discretion of the treating physician. Dose escalation followed a standard 3+3 design with an expansion for 6 additional patients at the maximal tolerated dose (MTHD). Dose limiting toxicity (DLT) was defined as grade 3 (G3) toxicity lasting > 4 days that occurred during or up to 21 days following RT. Toxicity was scored during RT and for 2 years following completion using the CTCAE v4.0. Toxicity was considered acute within 90 days of RT and late after 90 days. RESULTS Between 01/2018 and 08/2019, 15 patients with a median age of 70 (47-76) underwent RT. Nine patients (60%) underwent concurrent ADT. Patients were classified as NCCN favorable-intermediate (n = 3), unfavorable-intermediate (n = 2), high-risk (n = 9), and very-high risk (n = 1). Three patients were treated at DL1, 3 at DL2, and 9 at DL3. Median follow up was 24 months (9.7-24.0). One patient was removed from study at 9.7 months for PSA progression. There were no DLTs, and no patients required a treatment break. Nine patients (60%) experienced a maximum acute G2 GI toxicity. Within these 9 patients there were 11 total acute G2 GI events consisting of diarrhea in 1 patient (duration: 37 days), proctitis in 5 patients (median duration: 25 days), and worsening hemorrhoids in 5 patients (median duration: 17 days, all occurred in patients with baseline G1 hemorrhoids). One patient developed acute G3 GI toxicity (proctitis) on DL3 which resolved to G2 with medical management in < 4 days. No acute G2 or G3 GU toxicities were observed, however acute G1 dysuria was common (n = 6). Late G2 GI and GU toxicity each occurred in 3 patients respectively. Late G3 GU toxicity occurred in 2 patients (self-limited hemorrhagic cystitis in a patient on DL2, worsening of baseline incontinence in a patient on DL3). There were no ≥ G4 acute or late toxicities. CONCLUSION The MTHD for hypofractionated post-operative radiotherapy to the prostate bed was 44.2 Gy in 10 daily fractions. Consistent with recent reports on hypofractionation in the intact prostate setting, acute ≥G2 GI toxicity was observed frequently. Late toxicity rates were similar to rates reported in these prior studies.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

Background: Primary (PAS) and secondary angiosarcoma (SAS) of breast account for < 1% of all breast neoplasms. SAS develops following radiation therapy (RT) to the breast or chest wall for treatment of breast cancer. The rarity of this tumor type makes it challenging to determine prognostic factors and develop optimal treatment strategies. Historically, large NCI cancer centers have reported a median overall survival ranging from 28 – 100 months with recurrence rate of 55%. Methods: We reviewed demographic, tumor, and treatment characteristics of breast AS patients diagnosed and treated at our institution between 1990 and 2015. Overall (OS) and recurrence free (RFS) survival were compared using standard statistical methods at a significance level of 0.05. Results: Of 12155 breast cancers, 22 patients (0.008%) with AS (PAS in 34%, SAS in 66%) were identified. Median age of PAS patients was significantly lower than SAS – 45 vs 71 years (p < 0.001). Median tumor size was 6.9 cm (7.3 cm vs 6.9 cm, p = 0.93) with multifocal disease seen in 22.7%. Tumor was high grade in 14 (50% vs 83.3%, p = 0.34). Median time from RT to SAS diagnosis was 7.8 years. Treatment included: mastectomy in 17 (77.3%), wide excision in 4 (18.2%), adjuvant RT in 4 (18.2%), taxane based chemotherapy in 11 (50%) and chemo-RT in 1 (4.5%). No significant differences were noted in tumor (p = 0.9) or treatment characteristics (p = 0.4) between PAS and SAS. Recurrence rate (mainly distant) was 36% (8 pts). The 5-year OS and RFS rates were 51% (95% CI 27–72%) and 36% (95% CI 14–58%) with estimated medians of 64.2 and 55.5 months, respectively with no significant difference between the two groups. Black ethnicity (11.6 vs 64.2 months, p = 0.015), multifocal disease (15.5 vs 64.2 months, p = 0.004) and tumor size of > 6.9 cm (8.3 vs 64.2 months, p = 0.03) were associated with poorer outcomes. Tumor grade was not related to OS. Adjuvant treatment (RT p = 0.49, chemotherapy p = 0.36) conferred no RFS or OS benefit. Conclusions: Patients with PAS were younger than SAS. Black race, multifocal presentation and larger tumor size predict worse clinical outcomes. Our institutional experience confirms the poor prognosis of angiosarcoma, and highlights the need for further research. Citation Format: Ammannagari N, Attwood K, Cheney R, Young JS, Kane JM, Salerno KE, Opyrchal M. Factors predicting treatment outcomes of angiosarcoma of breast: A 25 year single institution experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-41.

TPS4599 Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.

Purpose Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume–to–planning target volume (CTV-to-PTV) margin. Methods and materials Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. Results The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations ( P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction ( P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. Conclusions The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.

In the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer, among adjuvant radiotherapy options for whole-breast irradiation after breast-conserving surgery, hypofractionation is preferred. For the use of accelerated partial-breast irradiation, the NCCN Guidelines have adopted the updated definition of "suitability" used by the American Society for Radiation Oncology. Regional nodal irradiation is indicated-either in the setting of breast-conserving surgery or after mastectomy-for women with ≥4 positive nodes and should be strongly considered for 1 to 3 positive lymph nodes and select patients with node-negative disease deemed at high risk for recurrence.

The potentially curative treatment for soft tissue sarcomas is wide resection. When located on the scalp, this can require removal of significant volumes of adjacent soft tissues as well as the skull periosteum. Consequently, reconstruction of the surgical defect is challenging. For patients receiving preoperative radiation or chemotherapy, gradual tissue expansion through the placement of a preoperative tissue expander can allow for primary closure of the wide resection defect, typically with hair-bearing scalp.

Background Malignant adnexal tumors of the skin (MATS) are rare. We aimed to measure the survival of patients with MATS and identify predictors of improved survival. Methods A retrospective review of MATS treated at our institution from 1990 to 2012. Results There were 50 patients within the time period. Median age was 59.5 years (range 22–95); primary site was the head and neck (52%); most common histologic subtypes were skin appendage carcinoma (20%) and eccrine adenocarcinoma (20%); and the vast majority were T1 (44%). Most patients (98%) underwent surgical treatment. Chemotherapy and radiation were administered to 8 and 14% of patients, respectively. Recurrence rate was 12%. Median OS was 158 months (95% CI, 52–255). OS and recurrence-free survival at 5 years were 62.4 and 47.4% and at 10 years 56.7 and 41.5%, respectively. Five-year and 10-year disease-specific survival (DSS) was 62.9%. Age > 60 years was an unfavorable predictor of OS (HR 12.9, P

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

This chapter describes the evolution of therapy for locally advanced breast cancer. Optimal management requires coordinated multidisciplinary care. Current treatment paradigms for LABC include use of neoadjuvant chemotherapy; resection, usually with mastectomy and axillary lymph node dissection; and adjuvant radiation to the chest wall or breast and regional nodes.

Purpose Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results Treatment guidelines for preoperative RT for RPS are presented. Conclusions An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity.

Background Given the propensity for hematogenous metastases, neoadjuvant chemotherapy (NAC) could treat occult metastatic disease early, potentially improving survival and better defining which primary angiosarcomas (AS) benefit from surgical resection. Methods A retrospective comparison was performed of 23 patients with resectable, localized cutaneous/soft tissue primary AS treated with surgery alone (S, n = 13) or NAC followed by surgery (NAC-S, n = 12). Results Primary sites included breast/chest (n = 9), head/neck (n = 9), extremity (n = 3), and other (n = 2). 23% S versus 40% NAC-S had prior radiation (RT). NAC regimens were paclitaxel (n = 6) or gemcitabine/docetaxel (n = 4). Seventy percent were high grade. Distant metastases were found in 17% after NAC. Non-primary wound closure was required in 54 %S versus 30%NAC-S (P = 0.4). R0 resections were achieved in 85% S versus 80% NAC-S (30% had a complete pathologic response). Two-year local recurrence (LR)-free, disease-free, and overall survivals were 67.1, 38.5, and 61.5% for S versus 68.6, 54.9, and 68.6% for NAC-S (P = 0.52, 0.67, and 0.58). The mean number of surgical resections/patient to maintain local control was 1.8 S versus 1.3 NAC-S (P = 0.06). Conclusions NAC for primary AS was well tolerated. Although there was no statistically significant survival benefit, NAC helped define who would benefit from surgical resection. J. Surg. Oncol. 2015 111:829–833. © 2014 Wiley Periodicals, Inc.

Angiosarcoma (AS) and epithelioid hemangioendothelioma (EHE) are rare but clinically disparate vascular sarcomas. Common AS scenarios include the head and neck/scalp region in older patients or in association with chronic lymphedema or radiation therapy (often in the setting of breast cancer treatment). AS behaves like a high-grade tumor with a propensity for multifocality and hematogenous metastases. The potentially curative treatment is negative margin wide resection. Adjuvant radiation may be considered to does not reduce the risk of local recurrence. Unresectable localized tumor can be treated with definitive radiation therapy. Although data are limited, neoadjuvant and adjuvant chemotherapy are occasionally used. Extensive primary tumor or metastatic disease is treated with systemic therapy. EHE can arise in the liver, bone, lung, pleura, or skin/soft tissue and can also metastasize hematogenously. The tumor is frequently asymptomatic and can be clinically indolent. Therefore, specific therapy is reserved for documented progression. Limited primary tumor is treated with surgical resection and occasionally adjuvant radiation. There is no proven benefit to adjuvant chemotherapy. Liver-directed therapy and occasionally transplantation are used for unresectable hepatic disease. Metastatic disease is treated with systemic therapy, but only in the setting of clinical progression. Key words: angiosarcoma, breast, cutaneous, epithelioid hemangioendothelioma, lymphedema, neoadjuvant chemotherapy, radiation associated, visceral

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The NCCN Guidelines specific to management of large clinical stage II and III tumors are discussed in this article. These guidelines are the work of the members of the NCCN Breast Cancer Panel. Expert medical clinical judgment is required to apply these guidelines in the context of an individual patient to provide optimal care. Although not stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer.

76 Background: Use of prostate stereotactic body radiotherapy (SBRT) as treatment for localized prostate cancer (PCa) is increasing. Given the high dose (>5Gy) per fraction (Fx) being delivered, SBRT requires careful preparation and delivery to ensure accuracy and precision. Guidelines and data on best practice for bowel and bladder preparation are lacking. Therefore, we surveyed practicing radiation oncologists (RO) to document practice patterns for prostate SBRT. Methods: From June to October 2018 we completed a nationwide survey of 1395 American Society for Therapeutic Radiology and Oncology (ASTRO) members who self-identified as managing PCa. A SurveyMonkey link was sent via email, and analysis included practicing RO who treat PCa with SBRT. Results: 204 responses were received with 32% (64/204) using SBRT. 80% (51/64) provided the fractionation used: 33% (17/51) use 35Gy to 36.25Gy, and 17.6% (9/51) use >40Gy in 5 Fx, and 1 used >9Gy Fx. 94% use implantable devices for localization (83% fiducial markers, 17% radiofrequency transponders). 65% (42/64) use a hydrogel spacer. 75% (48/64) use daily cone beam CT (CBCT) for image guidance. The majority use a 5 mm PTV, with 3 mm posteriorly. For bladder and bowel preparation 97% (62/64) provided preferences. For bladder, 90.3% (56/62) required a comfortably full bladder for both simulation and treatment. For simulation, 92% (57/62) have a bowel protocol (BP) to optimize rectal reproducibility. 51.6% (31/62) have patients empty their bowels prior, and 51.6% (31/62) prescribe a BP. Diet alteration was recommended by 77% (48/62). 86% (53/62) used a BP during SBRT treatment. Of those using a BP, 67% (43/64) continued it throughout SBRT with 30% (19/64) continuing BP unless symptoms change management. Only 3% (2/64) stop BP after simulation. Conclusions: The variability of data in the literature on effective BP for treatment reproducibility for PCa is reflected in the varied patterns of practice seen in our survey. Consensus on bladder preparation is seen for a majority of practitioners. A variety of BP regimens are employed.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

The updates to management of early invasive breast cancer in 2016 are minor but have important treatment implications for patients. The NCCN Guidelines Panel for Breast Cancer has added endocrine therapy to its recommendations for the neoadjuvant treatment of patients with ER-rich tumors. For women who are premenopausal at diagnosis, the NCCN Guidelines suggest tamoxifen for 5 years, with or without ovarian suppression, or an aromatase inhibitor for 5 years combined with ovarian suppression or ablation. For HER2-positive patients, neoadjuvant pertuzumab is acceptable, and in advanced estrogen receptor-positive disease, palbociclib can be given with endocrine therapy. Hypofractionation is now the preferred approach for whole-breast irradiation after breast-conserving therapy. Regional nodal irradiation should be strongly considered for women with 1 to 3 positive lymph nodes and is indicated for those with 4 or more positive nodes.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org.

Female breast cancer accounts for 14% of all new cancer cases in the United States. Metaplastic breast carcinomas (MpBC) are less than 1% of all mammary tumors. Limited clinical information exists on the prognosis and treatments for MpBC due to its rarity and the histological diversity of the tumor cells. We report a case of metastatic MpBC with osseous differentiation who had a marked response to liposomal doxorubicin. This 54-year-old female presented with a 2.5 x 2.6 cm oval-shaped irregularly marginated density in the outer lower quadrant of the left breast, cT2N0M0. Biopsy revealed an invasive metaplastic carcinoma, triple negative, with osseous and focal chondroid differentiation. Genetic testing showed a mutation in the BRCA1 gene. Approximately seven months after a left mastectomy, the patient presented with biopsy-proven metastatic disease and was initiated on therapy with a single agent, liposomal doxorubicin, 50 mg/m(2) every 28 days. The patient achieved maximum response after cycle three and continued to have stable disease for 18 months (20 cycles). Based on the pathologic phenotype, we would have predicted that she would have had a poor and short response to anthracycline. This case illustrates an increased sensitivity of BRCA1-mutated cancers to anthracycline therapies, irrespective of pathologic classification.

Soft tissue sarcomas (STS) are a rare and heterogeneous group of tumors arising from mesenchymal tissue comprising 1% of all adult cancers. The prognosis of metastatic STS is dismal. As there are few active drugs, there is a critical need to find new therapeutic alternatives in order to improve outcomes. Most sarcoma subtypes are fairly resistant to standard chemotherapy regimens and/or have a short duration of response. The era of molecular targeted therapy may present new treatment options for metastatic STS and an opportunity to drive biomarker discovery and personalized medicine. This case report describes a patient with a synchronous metastatic high-grade sarcoma who was treated with BRAF-targeted therapy with resolution of his metastatic lesions. To our knowledge, this exceptional response has not been described in sarcoma literature. The patient presented with a large anterior abdominopelvic wall mass. Biopsy showed a high-grade spindle cell sarcoma. Staging scans confirmed two pulmonary metastases. He was initiated on combination chemotherapy with mixed results. He received 50 Gy of radiation to the primary tumor followed by two additional cycles of combination chemotherapy, with an interval increase in the size of the pulmonary metastases. Molecular testing revealed a BRAF V600E mutation in the primary tumor. The patient was initiated on dabrafenib/trametinib with a dramatic response and resolution of his pulmonary metastases. The patient underwent surgical resection of his primary mass, and pathology confirmed no evidence of residual disease. Detailed genetic characterization of STS coupled with novel therapeutic strategies, including molecular targeted therapy, may have the potential to transform the care of patients diagnosed with sarcoma.

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.

e23525Background: PAS and SAS are very rare tumors that share similar clinical presentations despite biological difference. Literature provides scarce and often conflicting description of variables...