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Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.

IMPORTANCE Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases.OBJECTIVE To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases. DESIGN, SETTING, AND PARTICIPANTSThis prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for Ն4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions. MAIN OUTCOMES AND MEASURESThe primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (Ն2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT. RESULTSIn this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT.CONCLUSIONS AND RELEVANCE Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival.

OBJECTIVEEnhanced Recovery After Surgery (ERAS) programs follow a multimodal, multidisciplinary perioperative care approach that combines evidence-based perioperative strategies to accelerate the functional recovery process and improve surgical outcomes. Despite increasing evidence that supports the use of ERAS programs in gastrointestinal and pelvic surgery, data regarding the development of ERAS programs in spine surgery are scarce. To evaluate the impact of an Enhanced Recovery After Spine Surgery (ERSS) program in a US academic cancer center, the authors introduced such a program and hypothesized that ERSS would have a significant influence on meaningful clinical measures of postoperative recovery, such as pain management, postoperative length of stay (LOS), and complications.METHODSA multimodal, multidisciplinary, continuously evolving team approach was used to develop an ERAS program for all patients undergoing spine surgery for metastatic tumors at The University of Texas MD Anderson Cancer Center from April 2015 through September 2016. This study describes the introduction of that ERSS program and compares 41 patients who participated in ERSS with a retrospective cohort of 56 patients who underwent surgery before implementation of the program. The primary objectives were to assess the effect of an ERSS program on immediate postoperative pain scores and in-hospital opioid consumption. The secondary objectives included assessing the effect of ERSS on postoperative in-hospital LOS, 30-day readmission rates, and 30-day postoperative complications.RESULTSThe ERSS group showed a trend toward better pain scores and decreased opioid consumption compared with the pre-ERSS group. There were no significant differences in LOS, 30-day readmission rate, or 30-day complication rate observed between the two groups.RESULTSAn ERSS program is feasible and potentially effective on perioperative pain control and opioid consumption, and can expedite recovery in oncological spine surgery patients. Larger-scale research on well-defined postoperative recovery outcomes is needed.

BackgroundSoft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.MethodsThere is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy.DiscussionThis study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma.Trial registrationClinicalTrials.gov NCT03307616, registered October 12, 2017.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4829-0) contains supplementary material, which is available to authorized users.