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Myxofibrosarcoma is one of the most common types of soft tissue sarcomas occurring in the lower limbs of male older adults. Mainstay treatment is surgical intervention with chemoradiotherapy with a combination of doxorubicin and ifosfamide with brachytherapy if advanced or metastatic. There are no guidelines on the combination of immunotherapy with radiation therapy for myxofibrosarcoma. We report the first documented case of unresectable multifocal myxofibrosarcoma that was treated with pembrolizumab and radiation therapy for first-line therapy with a significant response. We also highlight genomic markers and immune radiation priming therapy, forecasting favorable response in treatment with pembrolizumab. [ABSTRACT FROM AUTHOR]

Simple Summary: Y-90 Selective Internal Radiotherapy (SIRT) uses injectable radioactive microspheres to treat inoperable liver metastases. It is poorly understood how the effective local control of small-volume metastatic disease with Y-90 SIRT may improve patient survival. Here, we demonstrate that failure to locally control liver metastases with ytrritum-90 (Y-90) SIRT is associated with worse 1-year overall survival for patients with ≤5 metastases, emphasizing the importance of disease control in those with early metastatic disease. Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients. [ABSTRACT FROM AUTHOR]

Despite introduction of various novel therapies, treatment options for metastatic castrate resistant prostate cancer (mCRPC) remain limited. This is a retrospective, multi-institution study of 43 patients with mCRPC treated with oral metronomic cyclophosphamide (mCyc), which showed promising, rapid, durable activity and a tolerable toxicity profile in a heavily-pretreated mCRPC population with aggressive clinical, pathologic, and genomic disease features. Introduction: Despite the introduction of various novel therapies for management of metastatic castrate resistant prostate cancer (mCRPC) in recent decades, available treatment options are finite and remain limited. Multiple historical studies have demonstrated activity and a favorable toxicity profile of oral metronomic cyclophosphamide (mCyc) in prostate cancer (PCa). Unlike the cytotoxic immunosuppressive effects of high-dose intravenously-administered cyclophosphamide, continuous low doses of oral mCyc have a unique immune-stimulatory mechanism of action. Materials and Methods: This is a retrospective, multi-institution study of men with 43 patients with mCRPC treated mCyc. Patient demographic information as well as clinical, pathologic, and genomic characteristics of their PCa were extracted. The primary endpoint was the rate of PSA decline by = 50% (ie, PSA50). Additional efficacy and toxicity data as well as cost analysis compared to other commonly used agents in mCRPC was obtained. Results: PSA50 was noted in 20.9% of patients, while an additional 25.6% patients achieved < PSA50 and 6.9% reported improvement in prostate cancer-related symptoms without any PSA reduction. Meanwhile, 9.3% of patients required mCyc dose reduction, 11.6% needed dose interruption due to toxicity, and no treatment discontinuations due to toxicity were observed. mCyc was also cost effective compared to other agents commonly used in mCRPC. Conclusions: Despite the small sample size and retrospective nature of this dataset, mCyc demonstrated promising rapid activity and a tolerable toxicity profile in a heavily pretreated mCRPC population with aggressive clinical, pathologic, and genomic disease features. [ABSTRACT FROM AUTHOR]

The prognosis for patients with penile squamous cell carcinoma metastatic to regional lymph nodes or distant sites remains poor with limited treatment options, especially after the failure of first-line chemotherapy. Clinical trials evaluating the use of checkpoint inhibitor therapy, or the use of checkpoint inhibitor therapy with stereotactic body radiation therapy for the treatment of metastatic penile squamous cell carcinoma, are currently unavailable. In this case report, we present a patient with relapsed advanced penile squamous cell carcinoma and an unknown (human papilloma virus) HPV status and borderline programmed death-ligand 1 (PD-L)1 status who was treated with pembrolizumab and stereotactic body radiation therapy. This patient achieved a complete durable treatment response despite having genomic features of an immunologically "cold" tumor. This case highlights the importance of investigating more into the treatment of these tumors that lack genomic features that classically have been observed to be susceptible to treatment with immunotherapy or immunotherapy augmented with stereotactic body radiation therapy in solid tumors, particularly in metastatic penile squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk. Methods: Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions). Results: For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT and IMPT. Conclusions: BgRT has the potential to reduce the radiation dose to proximal critical structures but requires further detailed investigation. [ABSTRACT FROM AUTHOR]

Current guidelines recommend neoadjuvant (NAC) and/or adjuvant chemotherapy for locally advanced gastric cancers (LAGCs). However, the choice and duration of NAC regimen is standardized, rather than personalized to biologic response, despite the availability of several different classes of agents for the treatment of gastric cancer (GC). The current trial will use a tumor-informed ctDNA assay (Signatera™) and monitor response to NAC. Based on ctDNA kinetics, the treatment regimen is modified. This is a prospective single center, single-arm, open-label study in clinical stage IB-III GC. ctDNA is measured at baseline and repeated every 8 weeks. Imaging is performed at the same intervals. The primary end point is the feasibility of this approach, defined as percentage of patients completing gastrectomy. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review describes recent data supporting locoregional ablative radiation in the treatment of oligometastatic colorectal cancer liver metastases. Recent Findings: Stereotactic body radiotherapy (SBRT) demonstrates high rates of local control in colorectal cancer liver metastases when a biologically equivalent dose of > 100 Gy is delivered. Future innovations to improve the efficacy of SBRT include MRI-guided radiotherapy (MRgRT) to enhance target accuracy, systemic immune activation to treat extrahepatic disease, and genomic customization. Selective internal radiotherapy (SIRT) with y-90 is an intra-arterial therapy that delivers high doses to liver metastases internally which has shown to increase liver disease control in phase 3 trials. Advancements in transarterial radioembolization (TARE) dosimetry could improve local control and decrease toxicity. Summary: SBRT and SIRT are both promising options in treating unresectable metastatic colorectal cancer liver metastases. Identification of oligometastatic patients who receive long-term disease control from either therapy is essential. Future advancements focusing on improving radiation design and customization could further improve efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Patients diagnosed with metastatic sarcoma have limited options for achieving both local and distant tumor control. While SBRT can achieve local control, distant response rates remain low. There is limited evidence demonstrating the safety and efficacy for combining SBRT with concurrent PD-1 checkpoint blockade in metastatic sarcoma. In this prospective case-series, we examined five patients with metastatic sarcoma on pembrolizumab treated concurrently with SBRT from July 1, 2016–October 30, 2018. Acute and chronic toxicity were recorded using Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). SBRT-treated tumor control was assessed using Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). With median follow-up of 14.9 months, three patients with undifferentiated pleomorphic sarcoma, one with intimal, and one with chondroblastic osteosarcoma received SBRT with concurrent pembrolizumab to 10 sites of metastatic disease. No grade 5 toxicities were observed. There was a single incidence of transient grade 4 lymphopenia which resolved without intervention. Grade 3 toxicities included anemia, thrombocytopenia, lymphopenia and colitis. One tumor demonstrated local progression after SBRT, and all others remained stable or with response. In conclusion, combining SBRT with PD-1 inhibition appeared to be safe in this patient population. Expected high rates of treated-tumor local control after SBRT were observed. Two of five patients demonstrated either enhanced local tumor regression, or possible abscopal effect. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection. Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1. Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months. Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed. [ABSTRACT FROM AUTHOR]

Aim: To explore management trends in preinvasive and cT1-T3 penile cancer. Materials & methods: The National Cancer Database was queried (2004-2013) for cT1-T3 M0 penile cancer with specified nonpalliative surgical techniques and histologies (n = 5,728). Results: Local excision (39%) and partial penectomy (38%) were most commonly utilized. Patients with cTis/Ta or cT1 disease more often received nonpenectomy approaches (p < 0.05); cT2-T3 cases more likely underwent penectomy (p < 0.001). No survival differences were observed between penectomy (49.3 months) and nonpenectomy approaches (50.3 months) in the overall cohort (p = 0.107) and when stratifying by T-stage (p > 0.20 for all). Conclusion: This study provides contemporary insight into the landscape for management of this rare disease and can serve as a benchmark for future evaluation of treatment trends. [ABSTRACT FROM AUTHOR]

Aims: To analyze outcomes in primary anorectal melanoma, a rare disease with limited data and treatment guidelines. Materials & methods: We analyzed 305 subjects in the National Cancer Database from 2004 to 2015. The primary end point was overall survival (OS). Results: Surgery was predictive of OS (median 2.24 vs 1.18 years; p = 0.009) with no survival difference between local and transabdominal approaches (p = 0.77). No OS benefit was seen with chemotherapy (p = 0.16), radiotherapy (p = 0.31) or adjuvant therapy post surgery (p > 0.05 for all groups). Targeted therapy trended toward higher survival in metastatic patients (1.33 vs 0.55 years; p = 0.06). Conclusion: In nonmetastatic patients, surgery of any method is associated with a survival benefit. The trend for improved survival following targeted therapy in metastatic patients merits further exploration. [ABSTRACT FROM AUTHOR]

Aims: To analyze outcomes in primary anorectal melanoma, a rare disease with limited data and treatment guidelines. Materials & methods: We analyzed 305 subjects in the National Cancer Database from 2004 to 2015. The primary end point was overall survival (OS). Results: Surgery was predictive of OS (median 2.24 vs 1.18 years; p = 0.009) with no survival difference between local and transabdominal approaches (p = 0.77). No OS benefit was seen with chemotherapy (p = 0.16), radiotherapy (p = 0.31) or adjuvant therapy post surgery (p > 0.05 for all groups). Targeted therapy trended toward higher survival in metastatic patients (1.33 vs 0.55 years; p = 0.06). Conclusion: In nonmetastatic patients, surgery of any method is associated with a survival benefit. The trend for improved survival following targeted therapy in metastatic patients merits further exploration. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the utility of pretreatment and 3-month 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) standardized uptake value (SUV) in predicting and assessing recurrence in T3-T4 laryngeal carcinoma treated with definitive radiation therapy (RT). Methods: Patients with newly diagnosed T3-T4 laryngeal squamous cell carcinoma treated with definitive RT from 2004 to 2014 were reviewed. Patients who underwent pretreatment or 3-month PET/CT 2 to 4 months after treatment were included. Those with prior systemic, surgical, or RT treatment were excluded. The primary objective was to assess whether pretreatment or posttreatment maximum SUV of the primary site (pSUV) of disease was associated with local recurrence-free survival. Overall survival was a secondary end point. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the accuracy of 3-month PET/CT at the larynx primary. Results: Twenty-eight patients were eligible for analysis. Median follow-up time was 34.7 months (range, 5.3-138.7 months), and median age was 57 years. Most patients had supraglottic (71.4%), T3 (89.3%), N2 (50.0%) disease, received chemotherapy (96.4%), and had histories of tobacco use (96.4%). On univariate analysis, 3-month posttreatment pSUV was associated with local recurrence-free survival (P < .01), while pretreatment pSUV was not (P = .41). No other associations were found with local recurrence-free survival. Neither pretreatment nor 3-month pSUV was significantly associated with overall survival. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of 3-month PET/CT at the primary site were 33%, 85%, 40%, and 81%, respectively. Conclusions: High initial fluorodeoxyglucose uptake in T3-T4 laryngeal primaries did not show an association with the risk for postradiation local relapse or overall survival, while increased fluorodeoxyglucose uptake at 3 months was associated with increased local recurrence. At 3 months, the relatively low sensitivity and positive predictive value may limit the utility of PET/CT in the assessment of persistent advanced laryngeal cancer after definitive radiation. [ABSTRACT FROM AUTHOR]

Background: Malignant melanomas on skin graft recipient sites are rare, with few cases reported in the literature. Methods: We present a case report of a patient with recurrent cutaneous melanoma in the grafted anterolateral thigh flap of the tongue. Results: A patient underwent hemiglossectomy with free flap reconstruction for squamous cell carcinoma of the tongue. Five years later the patient was seen with a 1‐cm nodule and surrounding erythroplakia at the recipient site of the graft. Analysis revealed cutaneous malignant melanoma. Patient then related a remote history of a suspected skin melanoma of the donor leg that had been treated with excision, with unknown histology. Conclusion: This may be the first reported case of a cutaneous malignant melanoma in the oral cavity following an anterolateral thigh free flap reconstruction, emphasizing the importance of obtaining a comprehensive history of skin cancers and closely inspecting the donor site prior to graft harvesting. [ABSTRACT FROM AUTHOR]

Background: In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1) and secondary (S2) somatosensory cortical activation, whereas a preceding painful stimulus results in facilitation. Methodology/Principal Findings: Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS) and in subjects with masochistic behaviour (MB) by means of a 122-channel whole-head magnetoencephalography (MEG) system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS) followed by a tactile test stimulus (TS) 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency. Conclusion: The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience. [ABSTRACT FROM AUTHOR]

The ability of tumors to evade detection by the immune system via inducing immunosuppression prompted the therapeutic development of immune checkpoint inhibitors. In our recent review, we discussed findings from preclinical and clinical investigations of these agents utilized in combination with radiation inducing abscopal (systemic) antitumor effects. [ABSTRACT FROM PUBLISHER]