Radiation Therapy Combined With Checkpoint Blockade Immunotherapy for Metastatic Undifferentiated Pleomorphic Sarcoma of the Maxillary Sinus With a Complete Response

Background: Undifferentiated pleomorphic sarcoma (UPS) of the maxillary sinus is an extremely rare malignancy of the head and neck. Surgery is the mainstay of treatment for UPS; however, proximity to vital structures makes it challenging to achieve negative surgical margins. Adjuvant therapy including radiation therapy with or without chemotherapy is generally indicated. Despite advances in multimodality treatment, objective response rates to available therapies and prognosis of metastatic UPS remain dismal. Immunotherapy has become a fourth cornerstone of cancer therapy and checkpoint blockade immunotherapy is a standard of care for recurrent or metastatic cisplatin-refractory head and neck squamous cell carcinoma. Checkpoint blockade immunotherapy is being studied in metastatic sarcoma, including UPS, and while initial results are promising, objective response rates remain below 20%. However, adding radiation therapy to checkpoint blockade immunotherapy has been shown, in both preclinical and retrospective clinical studies, to have combinatorial effects on both local and metastatic disease. Thus, further investigation into the effects of radiation therapy combined with immunotherapy in head and neck sarcomas is warranted.Case Presentation: We present a case of metastatic, chemotherapy-refractory, UPS of the maxillary sinus in a 55-year-old male treated with checkpoint blockade immunotherapy combined with radiation, which resulted in a complete response.Conclusions: This is the first report to our knowledge of metastatic UPS treated with a combination of radiation and dual agent checkpoint blockade immunotherapy. Further investigation is warranted to study the effects of this combination in patients with metastatic UPS that fail to respond to currently available therapies

PREVIS: Predictive visual analytics of anatomical variability for radiotherapy decision support

Radiotherapy (RT) requires meticulous planning prior to treatment, where the RT plan is optimized with organ delineations on a pre-treatment Computed Tomography (CT) scan of the patient. The conventionally fractionated treatment usually lasts several weeks. Random changes (e.g., rectal and bladder filling in prostate cancer patients) and systematic changes (e.g., weight loss) occur while the patient is being treated. Therefore, the delivered dose distribution may deviate from the planned. Modern technology, in particular image guidance, allows to minimize these deviations, but risks for the patient remain. We present PREVIS: a visual analytics tool for (i) the exploration and prediction of changes in patient anatomy during the upcoming treatment, and (ii) the assessment of treatment strategies, with respect to the anticipated changes. Records of during-treatment changes from a retrospective imaging cohort with complete data are employed in PREVIS, to infer expected anatomical changes of new incoming patients with incomplete data, using a generative model. Abstracted representations of the retrospective cohort partitioning provide insight into an underlying automated clustering, showing main modes of variation for past patients. Interactive similarity representations support an informed selection of matching between new incoming patients and past patients. A Principal Component Analysis (PCA)-based generative model describes the predicted spatial probability distributions of the incoming patient's organs in the upcoming weeks of treatment, based on observations of past patients. The generative model is interactively linked to treatment plan evaluation, supporting the selection of the optimal treatment strategy. We present a usage scenario, demonstrating the applicability of PREVIS in a clinical research setting, and we evaluate our visual analytics tool with eight clinical researchers

Salvage image guided radiation therapy to the prostate after cryotherapy failure

Purpose: Cryotherapy is an option for the primary treatment of localized prostate cancer, along with radical prostatectomy, external beam radiation therapy, and brachytherapy. Although it is known that local recurrence can occur in >20% of patients treated with primary cryotherapy, unfortunately there is a paucity of data on later salvage treatments. The use of external beam radiation therapy is an attractive option after cryotherapy failure, but there is little data on its efficacy and toxicity. We evaluated the biochemical control and complication rates of salvage dose-escalated image guided intensity modulated radiation therapy (IG-IMRT) after cryotherapy failure. Methods and materials: Patients who were treated at our institution from 2005 to 2016 were reviewed for those who underwent cryotherapy as initial treatment followed by salvage IGRT. Patients were treated with dose-escalated IG-IMRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily cone beam computed tomography or kv imaging to implanted fiducial markers. Biochemical progression was defined in accordance with the Phoenix consensus conference definition. Results: Eight patients were identified as having received post-cryotherapy salvage radiation within the study period. The median total dose was 77.7 Gy (range, 75.6-81.0 Gy). Median follow-up was 55 months (range, 6-88 months). Six patients remained biochemically controlled at the latest follow-up. One patient developed distant metastases after 22 months and one experienced biochemical failure at 30 months with no evidence of distant metastases. No patients experienced acute gastrointestinal toxicities of grade 2 or higher. There were no cases of late gastrointestinal or genitourinary toxicity. Conclusions: High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study

Bladder runner:visual analytics for the exploration of RT-induced bladder toxicity in a cohort study

\u3cp\u3eWe present the Bladder Runner, a novel tool to enable detailed visual exploration and analysis of the impact of bladder shape variation on the accuracy of dose delivery, during the course of prostate cancer radiotherapy (RT). Our tool enables the investigation of individual patients and cohorts through the entire treatment process, and it can give indications of RT-induced complications for the patient. In prostate cancer RT treatment, despite the design of an initial plan prior to dose administration, bladder toxicity remains very common. The main reason is that the dose is delivered in multiple fractions over a period of weeks, during which, the anatomical variation of the bladder – due to differences in urinary filling – causes deviations between planned and delivered doses. Clinical researchers want to correlate bladder shape variations to dose deviations and toxicity risk through cohort studies, to understand which specific bladder shape characteristics are more prone to side effects. This is currently done with Dose-Volume Histograms (DVHs), which provide limited, qualitative insight. The effect of bladder variation on dose delivery and the resulting toxicity cannot be currently examined with the DVHs. To address this need, we designed and implemented the Bladder Runner, which incorporates visualization strategies in a highly interactive environment with multiple linked views. Individual patients can be explored and analyzed through the entire treatment period, while inter-patient and temporal exploration, analysis and comparison are also supported. We demonstrate the applicability of our presented tool with a usage scenario, employing a dataset of 29 patients followed through the course of the treatment, across 13 time points. We conducted an evaluation with three clinical researchers working on the investigation of RT-induced bladder toxicity. All participants agreed that Bladder Runner provides better understanding and new opportunities for the exploration and analysis of the involved cohort data.\u3c/p\u3

A case-control study using motion-inclusive spatial dose-volume metrics to account for genito-urinary toxicity following high-precision radiotherapy for prostate cancer.

Background and purposeThe risk of genitourinary (GU) toxicity is dose-limiting in radiotherapy (RT) for prostate cancer. This study investigated whether motion-inclusive spatial dose/volume metrics explain the GU toxicity manifesting after high-precision RT for prostate cancer.Material and methodsA matched case-control was performed within a cohort of 258 prostate cancer patients treated with daily cone-beam CT (CBCT)-guided RT (prescription doses of 77.4-81.0 Gy). Twenty-seven patients (10.5%) presented late RTOG GU ≥ Grade 2 toxicity and those without symptoms of toxicity prior treatment (N = 7) were selected as cases. Each case was matched with three controls based on pre-treatment GU symptoms, age, Gleason score, follow-up time, and hormone therapy. Thirteen CBCTs per patient were rigidly registered to the planning CT using the recorded treatment shifts, and the bladder was manually contoured on each CBCT. Planned and actually delivered dose/volume metrics (the latter averaged across the CBCTs) were extracted from the bladder and its subsectors, and compared between cases and controls (two-way ANOVA test).ResultsThere were no significant differences between planned and delivered dose/volume metrics; also, there were no significant differences between cases and controls at any dose level, neither for planned nor delivered doses. The cases tended to have larger bladder volumes during treatment than controls (221 ± 71 cm3 vs 166 ± 73 cm3; p = 0.09).ConclusionsHigh-precision RT for prostate cancer eliminates differences between planned and delivered dose distributions. Neither planned nor delivered bladder dose/volume metrics were associated to the remaining low risk of developing GU toxicity after high-precision radiotherapy for prostate cancer

A case-control study using motion-inclusive spatial dose-volume metrics to account for genito-urinary toxicity following high-precision radiotherapy for prostate cancer

Background and purpose: The risk of genitourinary (GU) toxicity is dose-limiting in radiotherapy (RT) for prostate cancer. This study investigated whether motion-inclusive spatial dose/volume metrics explain the GU toxicity manifesting after high-precision RT for prostate cancer. Material and methods: A matched case-control was performed within a cohort of 258 prostate cancer patients treated with daily cone-beam CT (CBCT)-guided RT (prescription doses of 77.4–81.0 Gy). Twenty-seven patients (10.5%) presented late RTOG GU ≥ Grade 2 toxicity and those without symptoms of toxicity prior treatment (N = 7) were selected as cases. Each case was matched with three controls based on pre-treatment GU symptoms, age, Gleason score, follow-up time, and hormone therapy. Thirteen CBCTs per patient were rigidly registered to the planning CT using the recorded treatment shifts, and the bladder was manually contoured on each CBCT. Planned and actually delivered dose/volume metrics (the latter averaged across the CBCTs) were extracted from the bladder and its subsectors, and compared between cases and controls (two-way ANOVA test). Results: There were no significant differences between planned and delivered dose/volume metrics; also, there were no significant differences between cases and controls at any dose level, neither for planned nor delivered doses. The cases tended to have larger bladder volumes during treatment than controls (221 ± 71 cm3 vs 166 ± 73 cm3; p = 0.09). Conclusions: High-precision RT for prostate cancer eliminates differences between planned and delivered dose distributions. Neither planned nor delivered bladder dose/volume metrics were associated to the remaining low risk of developing GU toxicity after high-precision radiotherapy for prostate cancer. Keywords: Prostate cancer, Bladder, Genitourinary toxicity, CBCT, DVH, Spatia