Pathologic response rates after neoadjuvant therapy for sarcoma: A single institution study

(1) Background: Pathologic necrosis of soft tissue sarcomas (STS) has been used to determine treatment response, but its relationship to neoadjuvant treatments remains indeterminate. In this retrospective, single institution study, we hypothesized that neoadjuvant chemoradiation (NA-CRT) yields higher rates of pathologic complete response (pCR) than neoadjuvant radiation (NA-XRT) or chemotherapy (NA-CT) alone. (2) Methods: Patients with extremity STS between 2011–2020 who received neoadjuvant treatment were included. pCR was defined as percent necrosis of the surgical specimen greater than or equal to 90%. (3) Results: 79 patients were analyzed. 51.9% of the population were male with a mean age of 58.4 years. 49.4% identified as Non-Hispanic White. Twenty-six (32.9%) patients achieved pCR while 53 (67.1%) did not. NA-CT (OR 15.82, 95% CI = 2.58–96.9, p = 0.003 in univariate (UVA) and OR 24.7, 95% CI = 2.88–211.2, p = 0.003 in multivariate (MVA), respectively) and NA-XRT (OR 5.73, 95% CI = 1.51–21.8, p = 0.010 in UVA and OR 7.95, 95% CI = 1.87–33.7, p = 0.005 in MVA, respectively) was significantly associated with non-pCR when compared to NA-CRT. The analysis also demonstrated that grade 3 tumors, when using grade 2 as reference, also had significantly higher odds of achieving pCR (OR 0.23, 95% CI = 0.06–0.80, p = 0.022 in UVA and OR 0.16, 95% CI = 0.04–0.70, p = 0.015 in MVA, respectively). (4) Conclusion: NA-CRT yields superior pCR compared to other neoadjuvant regimens. This extends to higher grade tumors

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Adjuvant Therapies in Metastatic Bone Disease

Bone is a common site of metastatic disease in both solid tumor and hematologic malignancies. Skeletal involvement of cancer and the complications from these metastases can produce significant morbidity including, but not limited to, pathologic fractures and pain, hypercalcemia, and spinal cord or nerve root compression with neurologic compromise. Modern therapeutic advances have been developed towards the preservation of independence and improvement in quality of life, specifically with loss of mobility and social functioning in patients with metastatic bone disease. As such, the management of bone metastases is often complex, requiring an interdisciplinary and multimodal approach among surgeons, radiation oncologists, and medical oncologists. The aim of this discussion is to highlight the current recommendations regarding adjuvant treatments – local and systemic – in metastatic bone disease, including both radiotherapy and pharmaceutical interventions

Musculoskeletal Metastasis From Soft-tissue Sarcomas: A Review of the Literature

Soft-tissue sarcomas are a rare and extremely heterogeneous group of cancers, representing <1% of all human malignancies. The lungs are the most common site of distant metastasis, followed by the bone, lymph nodes, liver, brain, and subcutaneous tissue. Clinical experience suggests that skeletal metastasis is part of the natural history affecting the prognosis and quality of life in these patients. Approximately 2.2% of patients have skeletal metastasis at diagnosis. However, up to 10% will develop skeletal metastasis after a mean interval of 21.3 months. Although systemic therapy with conventional chemotherapy remains the primary treatment modality for those with metastatic sarcoma, increased survival has been achieved in selected patients who receive multimodality therapy, including surgery, for their metastatic disease. The 5-year overall survival of patients with isolated bone metastases was 41.2% (26.9% to 54.9%), which decreased to 32.9% (21.2% to 45.1%) in the setting of combined bone and lung metastases. Moreover, the resection of the primary soft-tissue sarcoma is a predictor of survival, resulting in a 58% decrease in mortality after surgery (hazard ratio, 0.42, P = 0.013). Understanding the effect of these metastases on patient survival may influence imaging, surveillance, and treatment decisions

Abstract PO-027: Associations of radiomics features with tumor necrosis following chemotherapy and/or radiation therapy in patients with extremity soft tissue sarcoma

Abstract Introductory sentence: The purpose of this study is to identify MRI radiomic features of sarcomas pre and post treatment with radiation and/or chemotherapy that correlate with the level of necrosis demonstrated on pathology report upon tumor excision. Experimental procedures: Patients with soft tissue upper and lower extremity sarcomas and available pre- and post-treatment MRI exams were included in the study. For the purposes of this study we utilized T2 fat saturated imaging sequences. We employed MINT Lesion radiomics software for extraction of quantitative imaging data. The lesions Regions of Interest (ROIs) were manually contoured MRI scans before and after chemotherapy and/or radiation therapy. Following treatment, patients had their tumors excised with corresponding tumor necrosis data recorded. Using Pearson correlation statistics, the percent necrosis was compared to radiomic changes (delta-radiomics). Summary of data: Fifty-two patients, treated between 2012 and 2020 were included in the study. The clinical characteristics were: male – (56%) and female- (44%); type of sarcomas ranged from Liposarcoma, Leiomyosarcoma, Myxofibrosarcoma, among others; Grade 2-3; Treatment with radiation and/or chemotherapy of different doses and regimens. MRIs were acquired within 3 months before initiation of treatment and within 2 months after treatment. Surgery was subsequently performed within 2 months of last MRI scan. The average necrosis on final pathology was 68% +/- 33% std. Total of 41 radiomic features were extracted from the ROIs. Five of the delta-radiomics parameters were significantly correlated with necrosis (p-value < 0.05) and sixteen were marginally associated (p-value < 0.1). The significantly correlated radiomic features includes first and second order values representing the distribution of voxel intensities within the segmented image regions and the statistical inter-relationships between neighboring voxels, respectively. Conclusions: In this pilot study we identified delta-radiomics features, related to first order radiomic data, or increased voxel intensity, and second order radiomics, or increased vowel heterogeneity, associated with the level of necrosis within sarcomas post radiation and/or chemotherapy. This data will be followed up with larger patient samples and including additional sequences for delta-radiomics analysis, such as Diffusion Weighted Imaging and Dynamic Enhanced Contrast to develop prediction models for necrosis levels. Citation Format: James Grosso, Ty Subhawong, Radka Stoyanova, Raphael Yechieli, Crystal Seldon, Blase Prosperi. Associations of radiomics features with tumor necrosis following chemotherapy and/or radiation therapy in patients with extremity soft tissue sarcoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-027

A Review of Boron Neutron Capture Therapy: Its History and Current Challenges

MECHANISM OF ACTION: External beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when (10)B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting (10)B(n,α)(7)Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei ((4)He), and recoiling lithium-7 ((7)Li) atoms. The short range (5-9 μm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles. HISTORY: BNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use. CURRENT LIMITATIONS AND PROSPECTS: Recently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency

Bone marrow sparing in prostate cancer patients treated with Post-operative pelvic nodal radiotherapy – A proton versus photon comparison

•Pelvic salvage RT improves oncologic outcomes in prostate cancer patients.•Large treatment volumes can lead to unintended bone marrow suppression.•Bone marrow toxicity is represented by leukopenia and lymphopenia.•Bone marrow sparing can be achieved with IMPT and VMAT treatment plan optimization.•Mean dose to the bone marrow can be lowered more with IMPT compared to VMAT. Extending salvage radiotherapy to treat the pelvic lymph nodes (PLNRT) improves oncologic outcomes in prostate cancer (PCa). However, a larger treatment volume increases the extent of bone marrow (BM) exposure, which is associated with hematologic toxicity (HT). Given the potential long-term impact of BM dose in PCa, clinical studies on BM sparing (BMS) are warranted. Herein, we dosimetrically compared photon and proton plans for BMS. Treatment plans of 20 post-operative PCa patients treated with volumetric-modulated arc photon therapy (VMAT) PLNRT were retrospectively identified. Contours were added for the whole pelvis BM (WPBM) and BM sub-volumes: lumbar-sacral (LSBM), iliac (ILBM), and lower pelvis (LPBM). Three additional plans were created: VMAT_BMS, intensity-modulated proton therapy (IMPT), and IMPT_BMS. Normal tissue complication probabilities (NTCP) for grade >3 hematologic toxicity (HT3+) were calculated for the WPBM volumes. Compared to the original VMAT plan, mean doses to all BM sub-volumes were statistically significantly lower for VMAT_BMS, IMPT, and IMPT_BMS resulting in average NTCP percentages of 20.5 ± 5.9, 10.7 ± 4.2, 6.1 ± 2.0, and 2.5 ± 0.6, respectively. IMPT_BMS had significantly lower low dose metrics (V300cGy-V2000cGy) for WPBM and sub-volumes except for LPBM V2000cGy compared to VMAT_BMS and ILBM V20Gy compared to IMPT. In most cases, V4000cGy and V5000cGy within ILBM and LSBM were significantly higher for IMPT plans compared to VMAT plans. BMS plans are achievable with VMAT and IMPT without compromising target coverage or OARs constraints. IMPT plans were overall better at reducing mean and NTCP for HT3+ as well as low dose volumes to BM. However, IMPT had larger high dose volumes within LSBM and ILBM. Further studies are warranted to evaluate the clinical implications of these findings