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Purpose Interprofessional education (IPE) is gaining recognition as a means of improving health care delivery and patient outcomes. A primary goal of IPE is improved interprofessional collaboration (IPC). The multidisciplinary team in the radiation oncology clinic requires effective IPC for optimal delivery of radiation therapy. However, there are limited data on IPE and IPC in radiation oncology. This qualitative study aims to characterize IPC in radiation oncology. Methods and Materials Semistructured phone interviews were performed from June to August 2019 with radiation oncologists, nurses, dosimetrists, radiation therapists, medical physicists, and medical students across a single academic medical center and affiliated network sites. Interviews were recorded, de-identified, and transcribed verbatim. Resulting transcripts were analyzed using thematic analysis. Results Seventeen interviews were performed with 4 radiation oncologists, 2 nurses, 2 dosimetrists, 4 radiation therapists, 2 medical physicists, and 3 medical students. Thematic analysis identified 4 themes: (1) management of the radiation oncology clinic, (2) potential impact of interprofessional training in radiation oncology, (3) current climate of interprofessional education in radiation oncology, and (4) creating an interprofessional training program in radiation oncology. Each theme elicited between 2 and 7 subthemes. Conclusions From the analytical themes that emerged, it is hypothesized that misunderstanding professionals’ roles can lead to communication breakdown, which creates less efficient clinic management and disorganized patient care. Although other medical professionals shadow physicians during their training, physicians are not learning about other professions in the same way. Interviewees from each professional category recommend a formal shadowing program for radiation oncology trainees at the medical student or resident level. Having structured opportunities for IPE is important given competing demands of learners during medical student rotations and residency. This study suggests an unmet need for exposure of radiation oncology medical trainees to IPE with the ultimate goal of improving IPC in the radiation oncology clinic.

In this review, we discuss the oligometastatic state, with a focus on its current and future relevance within the field of radiation therapy. We first outline the scope of the problem and the evolving understanding of metastatic disease existing along a spectrum. We then transition to a discussion of the clinical data that led to the formulation of the oligometastatic hypothesis, delving in some detail into the clinical factors associated with improved outcomes in the setting of local therapy-whether surgical or radiotherapeutic. In particular, we highlight the marked limitations of using clinical criteria alone to determine the absence or presence of true extracranial oligometastatic disease. After this, we briefly discuss the radiation therapy literature that has recently demonstrated benefits in cancer-specific outcomes with ablative treatment of oligometastatic disease. We emphasize data in the setting of non-small cell lung cancer and prostate cancer and briefly discuss the importance of our enhanced ability to detect occult metastatic disease with improved imaging technologies. After noting that resulted and ongoing prospective trials of ablative radiation therapy use the most rudimentary of oligometastatic classifiers-number of metastases-as their inclusion criteria, we transition to our core argument: a growing body of preclinical and translational work aims to refine the definition of oligometastatic disease using molecular features. We address genomic, epigenetic, and immunologic features that have, across histology, demonstrated an improved ability to prognosticate when combined with classic clinical correlates of oligometastatic disease. We also discuss studies that suggest particular molecular targets which, when manipulated for therapeutic purposes, have the potential to revert the polymetastatic phenotype to the oligometastatic one. We conclude with what we believe are the repercussions of this work for radiation therapy trials and clinical practice, and the importance of enriching and supporting these inquiries for the future of our field.

In the era of cancer immunotherapy, there is significant interest in combining conventional cancer therapies, such as radiotherapy, with drugs that stimulate the immune system. The observation that ionizing radiation applied to murine tumors delays the growth of distant tumors (“abscopal effect”) and that this effect is potentiated by immunostimulatory drugs, led to clinical trials in which often only one lesion is irradiated in combination with immunotherapy drugs. The results of these initial clinical trials combining radio therapy and immunotherapy show that a meaningful abscopal effect is still infrequent. Recent preclinical data suggest that preexistent intratumoral T cells can survive radiation and contribute to its therapeutic effect. In this review, we discuss possible mechanisms underlying the preclinical/clinical discrepancies regarding the abscopal effect, and we propose the irradiation of multiple or all tumor sites in combination with systemic immunotherapy as a possible avenue to increase the efficacy of radio-immunotherapy.

Background Several studies have suggested that antiplatelet (AP) or anticoagulant (AC) therapy may improve outcome in men with prostate cancer. We evaluated the effects of AP/AC therapy and tested the hypothesis that platelet count may also be associated with outcomes. Methods A total of 482 patients received primary radiotherapy (median dose 72 Gy) for nonmetastatic prostate cancer; 49% received androgen deprivation therapy. NCCN risk was low/intermediate/high risk in 39%/39%/22%. AP/AC therapy and platelet counts were analyzed with respect to freedom from biochemical failure (FFBF, nadir+2), distant metastasis (FFDM), and cause specific survival (CSS). Results After a median follow‐up of 103 months, 10‐year FFBF, FFDM, and CSS were 77%, 92%, and 96%, respectively. The 10‐year cumulative incidence of BF and DM (with death as a competing event) was 19% and 7.0%, respectively. The 32% of men on AP/AC therapy had a lower incidence of 10‐year BF (P = .016) and a trend toward a lower incidence of DM (P = .084) and CSS (P = .091). In the entire cohort, lowest platelet quartile (platelet count, 482 men received primary radiotherapy for non‐metastatic prostate cancer and those men with pre‐treatment platelet count in the lowest quartile experienced worse 10‐year freedom from biochemical failure (61% vs 81%, P

Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02–2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21–3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Background Given similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs. Methods A total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment–related, physician-defined Radiation Therapy Oncology Group gastrointestinal (GI) and genitourinary (GU) toxicity. Covariates identified on univariate analysis for toxicity and disease control were examined on multivariable analysis. All statistical tests were 2-sided, and a P less than .05 was considered statistically significant. Results A total of 155 of 587 men (26.4%) had 1 or more MAs, most commonly to penicillin (n = 71), sulfa (n = 35), and aspirin or nonsteroidal antiinflammatory drugs (n = 28). On univariate analysis, men with MAs had superior 10-y FFBF (71.5% vs 63.5%, P = .02) and higher incidence of late GI grade 2 or higher (G2+; 20.6% vs 13.2%, P = .04) and grade 3 or higher (G3+; 7.5% vs 3.9%, P = .08) as well as late GU G2+ (42.5% vs 33.2%, P = .04) and G3+ (7.5% vs 3.0%, P = .02) toxicity than men without MAs. On multivariable analysis, MA history remained a statistically significant predictor of FFBF (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.43 to 0.93, P = .02), late G2+ GI (HR = 1.76, 95% CI = 1.06 to 2.90, P=.03), and G3+ GU (HR = 2.69, 95% CI = 1.16 to 6.27, P = .02) toxicity after controlling for corresponding covariates in each model. Conclusions Men with MAs had improved FFBF and increased treatment-related toxicity following radiotherapy for prostate cancer. MA history could be a relevant consideration in the management of men with localized prostate cancer.

Purpose: Immune checkpoint blockade (ICB) has improved outcomes for patients with non-small cell lung cancer (NSCLC). However, most patients experience disease progression. There is limited data regarding molecular predictors of progression, particularly in those patients predicted to respond most favorably. We used a next-generation sequencing (NGS) platform to identify genomic aberrations associated with clinical outcomes following ICB in NSCLC. Methods: We retrospectively reviewed stage III/IV NSCLC patients who received radiotherapy (RT) in our department and underwent NGS with OncoPlus, a 1212-gene hybrid capture genomic sequencing assay. We characterized tumor mutations and insertions/deletions for patients who received ICB as well as other systemic therapies and investigated their associations with clinical outcome. Results: 149 patients with stage III/IV NSCLC received RT from 2011-2019 and underwent OncoPlus. Median age was 65, median ECOG was 1, and 125 had a smoking history. 87% had adenocarcinoma. AJCC 8th edition staging: IIIA (n=24), IIIB (n=14), IIIC (n=3), IVA (n=16), and IVB (n=92). 79% had PD-L1 staining: 0% in 45 patients (38%), 1-49% in 34 (29%), and ≥50% in 38 (32%). All received RT to a median of 2 lesions (range 1-15); 48% received palliative RT and 52% received ≥1 course of definitive RT (conventional or ablative). The majority received systemic therapy: 68% (n=102) received chemotherapy, 55% (n=82) received ICB, and 30% (n=44) received targeted therapies. Median follow-up was 18 months (range 1-95); most experienced isolated distant failure (n=64, 43%) or regional/distant failure (n=35, 23%) following their first RT course. The most frequent pathogenic mutations/indels were TP53 (68%, n=101), KRAS (31%, n=45), CDKN2A (27%, n=40), STK11 (26%, n=39), EGFR (19%, n=28), and TP53/KRAS co-mutation (17%, n=26). We found CDKN2A mutation (25%)/deletion (75%) was associated with inferior median recurrence-free survival (RFS; 3 vs. 6 mo., p=0.013) and more markedly median OS (13 vs. 38 mo., p=0.015) compared to wild-type tumors. On multivariate Cox proportional hazards analysis including stage, ECOG, PD-L1 %, TMB, type of RT, and # of RT sites, CDKN2A loss was independently associated with 2.5-fold risk of progression (p=0.018) and 3.3-fold risk of death (p=0.05). In high TMB (top 25th%; n=21) or high PD-L1 (>50%; n=30) NSCLCs, CDKN2A loss was negatively associated with RFS (TMB p=0.005; PD-L1 p=0.034) and in the high PD-L1 cohort with a trend towards inferior OS (p=0.08). Conclusions: In a large cohort of stage III/IV NSCLC patients treated with systemic therapy and RT, NGS identified CDKN2A mutation/deletion as a predictor of ICB resistance and poor outcome. In the context of recent evidence for sensitivity to CDK4/6 inhibition of CDKN2A-deficient tumors, our findings raise the possibility of utilizing currently available targeted agents in the treatment of CDKN2A-deficient NSCLC patients progressing on ICB. Citation Format: Stanley I. Gutiontov, Sean Pitroda. CDKN2A mutation predicts immunotherapy resistance in stage III/IV NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 799.

Purpose: Some patients with previously treated, unresectable, recurrent or metastatic head and neck malignancies are not amenable to curative-intent treatment. Here, we investigated the quad-shot (RTOG 8502) regimen of hypofractionated proton radiotherapy (RT) in that patient population. Materials and Methods: From 2013 to 2015, 26 patients with recurrent or metastatic cancers were treated with palliative proton RT to the head and neck with quad shot (3.7 Gy twice daily for 2 days). Patient characteristics and survival data were reviewed. Results: Seventeen (65%) patients received ≥ 3 quad-shot cycles and 23 (88%) had prior head and neck RT. Overall palliative response was 73% (n = 19). The most common presenting symptom was pain (50%; n = 13), which improved in 85% (n = 22) of all patients. The overall grade-1 acute-toxicity rate was 58% (n = 15), and no acute grade 3 to 5 toxicities were observed. Conclusions: The proton quad-shot regimen demonstrates favorable palliative response and toxicity ...

The development of intensity-modulated radiotherapy (IMRT) has played a major role in improving outcomes and decreasing morbidity in patients with head and neck cancer. This review addresses this vital modality with a focus on the important role of the head and neck surgeon. The technique as well as its benefits and points of caution are outlined, the definitions of tumor and treatment volumes are discussed, and the dose and fractionation are detailed. Following this are several sections dedicated to the role of the head and neck surgeon in the planning of both definitive and postoperative radiotherapy to the primary site and neck. There is a focus throughout on anatomic and surgical considerations; commonly encountered situations are illustrated. With a deeper understanding of this technique and their own pivotal contribution to target delineation, head and neck surgeons will be poised to expand their role and improve cancer care for their patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2368-E2373, 2016.

Purpose This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47–168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.

Nanomaterials have been shown to have physical and chemical properties that have opened new avenues for cancer diagnosis and therapy. Nanoconstructs that enhance existing treatments for cancer, such as radiation therapy, are being explored in several different ways. Two general paths toward nanomaterial-enabled radiosensitization have been explored: (1) improving the effectiveness of ionizing radiation and (2) modulating cellular pathways leading to a disturbance of cellular homeostasis, thus rendering the cells more susceptible to radiation-induced damage. A variety of different agents that work via one of these two approaches have been explored, many of which modulate direct and indirect DNA damage (gold), radiosensitivity through hyperthermia (Fe), and different cellular pathways. There have been many in vitro successes with the use of nanomaterials for radiosensitization, but in vivo testing has been less efficacious, predominantly because of difficulty in targeting the nanoparticles. As improved methods for tumor targeting become available, it is anticipated that nanomaterials can become clinically useful radiosensitizers for radiation therapy.