Faculty Bibliography

Purpose/Objective(s): Radiation therapy-induced cell death produces cytosolic DNA that activates the cyclic GMP-AMP synthase (cGAS)-STimulator of INterferon Genes (STING) pathway, crucial for the induction of Type I interferons (IFN-I). Checkpoint inhibitor (CPI) resistance mechanisms have been linked to impaired IFN signaling. Preclinical data have shown STING agonists to reverse CPI resistance in tumors with prior exposure, particularly when used with anti-PD-1/PD-L1 therapies. TAK-676 (a synthetic STING agonist) potently modulates the innate immune system, leading to cytokine release, adaptive immune activation, and antitumor responses in preclinical studies (Appleman et al., AACR 2022). TAK-676 is being investigated as a single agent, and in combination with pembrolizumab, for advanced solid tumors, in a first-in-human phase 1 study (NCT04420884). TAK-676 is optimally designed for intravenous (IV) delivery, with a prolonged half-life in serum and enhanced tissue permeability, allowing access to tumor sites and lymphatic tissue. Following radiation therapy, TAK-676 has the potential to stimulate T-cell mediated antitumor immunity via STING-mediated IFN-I release, particularly when used with anti-PD-1/PD-L1 therapies. Here, we present a second phase 1 study to investigate the safety and preliminary antitumor activity of TAK-676 in combination with pembrolizumab following radiation therapy, in patients with advanced or metastatic NSCLC, TNBC, or SCCHN who have progressed on CPIs (NCT04879849). Materials/Methods: Patients aged >=18 years who progressed on CPIs and have >=2 lesions, of which one is targetable with radiation, are being enrolled. Patients receive 8 Gy x 3 followed by (after a minimum of 40 hours) escalating doses of IV TAK-676 on days 1, 8 and 15 of a 21-day cycle, and 200 mg of IV pembrolizumab on day 1 of each cycle until disease progression, intolerance, or withdrawal of consent. Dose escalation of TAK-676 will be guided by the Bayesian Optimal Interval design. At screening and between days 15-21 of cycle 1, patients with a safely accessible lesion outside of the radiation field will have paired biopsies collected once the pharmacologically active dose levels of TAK-676 have been observed. The primary objective is to determine the safety and tolerability of TAK-676 in combination with pembrolizumab following radiation therapy. Secondary objectives are to determine the recommended phase 2 dose of TAK-676 in combination with pembrolizumab following radiation therapy, and to assess the local (within the radiation field) and systemic (non-radiated lesions) preliminary antitumor activity. As of February 2022, ~10% of the planned patients have been enrolled.
Result(s): TBD
Conclusion(s): TBD
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PURPOSE/OBJECTIVE(S): Use of local therapy such as stereotactic body radiation therapy (SBRT) to treat oligometastatic malignancy is a well-established paradigm, but whether benefit extends to the oligoprogressive setting remains unclear. We present our institutional series of patients with oligometastatic or oligoprogressive malignancy treated with SBRT. MATERIALS/METHODS: We performed a retrospective study of patients with oligometastatic and oligoprogressive malignancy treated with SBRT between 2014 and 2019. Oligometastatic patients were defined as those with five or fewer metastatic lesions in total. Oligoprogressive patients were defined as those with more than five and up to twenty metastatic lesions in total, of which five or fewer metastases were progressing on current systemic therapy. Patients lacking complete treatment records or follow-up imaging were excluded. The study was approved by the NYU Institutional Review Board.
RESULT(S): A total of 114 patients were treated with 123 courses of SBRT, of which 96 treated oligometastasis and 27 treated oligoprogression. Primary sites of disease included lung (38%), prostate (20%), and GI (12%), as well as gynecologic, abdominal, and cutaneous malignancies. Median follow-up was 21 months. No grade 3 or higher radiation-related adverse events were reported. Patients with oligometastatic malignancy had longer 2-year overall survival (79% vs 59%; P=0.003), local control (73% vs 55%; P=0.01), and progression-free survival (26% vs 8%; P < 0.001), but similar freedom from new systemic therapy (36% vs 31%; P=0.8). This result held true in subgroup analysis regardless of lung vs non-lung primary site, and regardless of the presence or absence of a targetable mutation.
CONCLUSION(S): In this hypothesis-generating retrospective cohort study, patients with oligoprogressive malignancy treated with SBRT have similar freedom from new systemic therapy to patients with oligometastatic malignancy, strengthening the rationale for treating oligoprogressive malignancy with SBRT.
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Purpose: Multi-isocentric treatment delivery for CSI and TBI poses specific challenges for treatment delivery. We have developed a software tool to streamline all aspects of delivery for therapists and physicists at the machine, as well as to inform attending physicians of setup variability and image residuals at different locations.
Method(s): Our institution delivers VMAT-based CSI and TBI with up to 3 and 7 isocenters, respectively. A software tool was developed to assist with treatment delivery including initial patient setup, patient imaging, automatic calculation of the optimal global shift based on each isocenter's ideal shift, and automatic calculation of each isocenter's couch coordinates. Initial treatment couch coordinates are queried via the Eclipse scripting API. The global shift was calculated prioritizing the head isocenter for CSI treatments and the chest isocenter for TBI treatments by first maximizing residual tolerance at any other location prior to accepting any residual deviation at these locations. Maximum residuals tolerance was determined based on target margins, plan uncertainty and as per physician instructions. Delivery parameters are reported to a document uploaded to ARIA via API.
Result(s): The developed tool was employed for 11 cases. The software tool replaced the need for plan shift comments or instructions for therapists. In particular, its use eliminated the need to provide isocenter shifts to therapists by directly providing final couch parameters for treatment, greatly reducing the risk of delivery errors. The software effectively informed the therapists if any expected tolerance was surpassed, triggering a patient setup evaluation.
Conclusion(s): The described software tool is a core component to our multi-isocenter treatment programs and has streamlined delivery of these complex techniques that would otherwise require complicated instructions, including multiple shifts and on-the-fly calculations of optimal image alignment based on multiple imaging locations. This has substantially reduced the possibility of delivery errors

PURPOSE/OBJECTIVE:Treatment with radiation therapy (RT) can cause anxiety and distress for pediatric patients and their families. Radiation oncology teams have developed strategies to reduce the negative psychological impact. This survey study aimed to characterize these methods. METHODS AND MATERIALS/METHODS:A 37-item questionnaire was sent to all radiation oncology members of the Children's Oncology Group to explore strategies to improve the pediatric patient experience. The Wilcoxon rank-sum test was used to assess factors associated with use of anesthesia for older children. RESULTS:Surveys were completed by 106 individuals from 84/210 institutions (40%). Respondents included 89 radiation oncologists and 17 supportive staff. Sixty-one percent of centers treated ≤50 children per year. Respondents described heterogenous interventions. The median age at which most children no longer required anesthesia was 6 years (range: ≤3 years to ≥8 years). Routine anesthesia use at an older age was associated with physicians' lack of awareness of these strategies (P = .04) and <10 years of pediatric radiation oncology experience (P = .04). Fifty-two percent of respondents reported anesthesia use added >45 minutes in the radiation oncology department daily. Twenty-six percent of respondents planned to implement new strategies, with 65% focusing on video-based distraction therapy and/or augmented reality/virtual reality. CONCLUSIONS:Many strategies are used to improve children's experience during RT. Lack of awareness of these interventions is a barrier to their implementation and is associated with increased anesthesia use. This study aims to disseminate these methods with the goal of raising awareness, facilitating implementation, and, ultimately, improving the experience of pediatric cancer patients and their caregivers.

Management of patients with lung cancer continues to be challenging during the COVID-19 pandemic, due to the increased risk of complications in this subset of patients. During the COVID-19 surge in New York City, New York University Langone Health adopted triage strategies to help with care for lung cancer patients, with good surgical outcomes and no transmission of COVID-19 to patients or healthcare workers. Here, we will review current recommendations regarding screening and management of lung cancer patients during both a non-surge phase and surge phase of COVID-19.

The objectives for the treatment of Wilms tumor in both the Children's Oncology Group (COG) and the International Society of Paediatric Oncology (SIOP) have focused on improving cure rates and minimizing toxicity by limiting the use of radiation and doxorubicin. Although the timing of surgery is different in COG (upfront surgery) and SIOP (upfront chemotherapy with delayed surgery), both are effective strategies and have the same survival. Fewer patients are treated with radiotherapy in the SIOP trials but with higher doses. The prognostic significance of biological markers such as 1q gain and clinical outcomes with novel radiation techniques such as intensity modulated radiation therapy will be determined in upcoming clinical trials. A closer collaboration between COG and SIOP could help promote research and improve the clinical outcomes of children with Wilms tumor.

Purpose/UNASSIGNED:Quality assurance and continuing quality improvement are integral parts of any radiation oncology practice. With increasingly conformal radiation treatments, it has become critical to focus on every slice of the target contour to ensure adequate tumor coverage and optimal normal tissue sparing. Proton therapy centers open internationally with increasing frequency, and radiation oncologists with varying degrees of subspecialization apply proton therapy in daily practice. Precise treatment with proton therapy allows us to limit toxicity but requires in-depth knowledge of the unique properties of proton beam delivery. To address this need at our proton therapy center, we developed a comprehensive peer review program to help improve the quality of care that we were providing for our patients. Materials and Methods/UNASSIGNED:We implemented a policy of comprehensive peer review for all patients treated at our community proton facility starting in January 2013. Peer review begins at the time of referral with prospective cases being reviewed for appropriateness for proton therapy at daily rounds. There is then biweekly review of target contouring and treatment plans. Results/UNASSIGNED:During a 6-month period from June 2013 to November 2013, a total of 223 new patients were treated. Documentation of peer review at chart rounds was completed for 222 of the 223 patients (99.6%). An average of 10.7 cases were reviewed in each biweekly chart rounds session, with a total of 560 case presentations. The average time required for contour review was 145 seconds (±71 seconds) and plan review was 120 seconds (±64 seconds). Modifications were suggested for 21 patients (7.9%) during contour review and for 19 patients (6.4%) during treatment plan review. An average of 4 physicians were present at each session. Conclusions/UNASSIGNED:We demonstrated that the implementation of a comprehensive, prospective peer review program is feasible in the community setting. This article can serve as a framework for future quality assurance programs.