Evaluation of non-vendor magnetic resonance imaging sequences for use in bladder cancer magnetic resonance image guided radiotherapy.

Hybrid systems that combine Magnetic Resonance Imaging (MRI) and linear accelerators are available clinically to guide and adapt radiotherapy. Vendor-approved MRI sequences are provided, however alternative sequences may offer advantages. The aim of this study was to develop a systematic approach for non-vendor sequence evaluation, to determine safety, accuracy and overall clinical application of two potential sequences for bladder cancer MRI guided radiotherapy. Non-vendor sequences underwent and passed clinical image qualitative review, phantom quality assurance, and radiotherapy planning assessments. Volunteer workflow tests showed the potential for one sequence to reduce workflow time by 27% compared to the standard vendor sequence.

Quantitative analysis of diffusion weighted imaging in rectal cancer during radiotherapy using a magnetic resonance imaging integrated linear accelerator.

Background and purpose: Magnetic resonance imaging integrated linear accelerator (MR-Linac) platforms enable acquisition of diffusion weighted imaging (DWI) during treatment providing potential information about treatment response. Obtaining DWI on these platforms is technically different from diagnostic magnetic resonance imaging (MRI) scanners. The aim of this project was to determine feasibility of obtaining DWI and calculating apparent diffusion coefficient (ADC) parameters longitudinally in rectal cancer patients on the MR-Linac. Materials and methods: Nine patients undergoing treatment on MR-Linac had DWI acquired using b-values 0, 30, 150, 500 s/mm2. Gross tumour volume (GTV) and normal tissue was delineated on DWI throughout treatment and median ADC was calculated using an in-house tool (pyOsirix ®). Results: Seven out of nine patients were included in the analysis; all demonstrated downstaging at follow-up. A total of 63 out of 70 DWI were analysed (7 excluded due to poor image quality). An increasing trend of ADC median for GTV (1.15 × 10-3 mm2/s interquartile range (IQ): 1.05-1.17 vs 1.59 × 10-3 mm2/s IQ: 1.37 - 1.64; p = 0.0156), correlating to treatment response. In comparison ADC median for normal tissue remained the same between first and last fraction (1.61 × 10-3 mm2/s IQ: 1.56-1.71 vs 1.67 × 10-3 mm2/s IQ: 1.37-2.00; p = 0.9375). Conclusions: DWI assessment in rectal cancer patients on MR-Linac is feasible. Initial results provide foundations for further studies to determine DWI use for treatment adaptation in rectal cancer.

Survival outcomes for head and neck cancer patients with N3 cervical nodal metastases.

BACKGROUND: Management of metastatic N3 nodal disease from primary head and neck squamous cell carcinoma (HNSCC) is controversial. Recently, there has been a move to observation of the neck for those who achieve complete response (CR) after chemoradiotherapy (CRT). We sought to determine survival outcomes for N3 nodal disease, particularly for patients with human papilloma virus (HPV)-positive HNSCC. METHODS: We carried out a systematic search of MEDLINE and Embase for articles between 01/2008 and 12/2017. Articles on N3 nodal disease in HNSCC patients treated with CRT or surgery + adjuvant RT/CRT were included if they reported on oropharyngeal or HPV+ subgroups. Local control (LC), nodal control (NC), distant metastasis-free survival (DMFS), disease-free survival (DFS) or overall survival (OS) was assessed. RESULTS: Nine studies met the inclusion criteria. Eight of these studies (N = 5304) allowed further comparison: 4 were on CRT, 2 on surgery + RT/CRT and 2 on both. Four of these eight studies and the remaining included study reported on residual nodal disease on histology after neck dissection (ND) following CRT. Patients treated with CRT achieved LC rates of 77%-94% at 2-3 years; those who had a CR had LC of >90%. Better NC was noted in patients who achieved a CR. Three-year OS was better for HPV+ HNSCC (range, 55.2%-81%). Patients with CR had better survival outcomes (DMFS 77% at 3 years vs 69.8% for HPV+; OS 68.9% at 3 years vs 55.2% for HPV+). Primary surgery demonstrated similar survival for HPV+ vs HPV- and better survival in oropharyngeal cancers. Five-year DFS rates varied from 30% to 87%, and OS from 26.6% to 84%. For patients with non-CR, positive histology rates varied from 27.3% to 100%, with average positive histology rates of 27.3% in HPV+ patients with non-CR vs 60% for HPV- patients with non-CR. CONCLUSION: The current literature does not support the de-escalation of treatment with HPV- N3 disease. Observation of HPV+ patients who achieve a CR post-CRT is reasonable but further prospective studies are required given the heterogeneity and risk of bias within these current studies. Planned ND should remain standard of care for non-CR cohort.

Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer.

Importance: Gut dysbiosis impairs response to immune checkpoint inhibitors (ICIs) and can be caused by broad-spectrum antibiotic (ATB) therapy. Objective: To evaluate whether there is an association between ATB therapy administered concurrently (cATB) or prior (pATB) to ICI therapy and overall survival (OS) and treatment response to ICI therapy in patients with cancer treated with ICIs in routine clinical practice. Design, Setting, and Participants: This prospective, multicenter, cohort study conducted at 2 tertiary academic referral centers recruited 196 patients with cancer who received ICI therapy between January 1, 2015, and April 1, 2018, in routine clinical practice rather than clinical trials. Main Outcomes and Measures: Overall survival calculated from the time of ICI therapy commencement and radiologic response to ICI treatment defined using the Response Evaluation Criteria in Solid Tumors (version 1.1), with disease refractory to ICI therapy defined as progressive disease 6 to 8 weeks after the first ICI dose without evidence of pseudoprogression. Results: Among 196 patients (137 men and 59 women; median [range] age, 68 [27-93] years) with non-small cell lung cancer (n = 119), melanoma (n = 38), and other tumor types (n = 39), pATB therapy (HR, 7.4; 95% CI, 4.3-12.8; P < .001), but not cATB therapy (HR, 0.9; 95% CI, 0.5-1.4; P = .76), was associated with worse OS (2 vs 26 months for pATB therapy vs no pATB therapy, respectively) (hazard ratio [HR], 7.4; 95% CI, 4.2-12.9) and a higher likelihood of primary disease refractory to ICI therapy (21 of 26 [81%] vs 66 of 151 [44%], P < .001). Overall survival in patients with non-small cell lung cancer (2.5 vs 26 months, P < .001), melanoma (3.9 vs 14 months, P < .001), and other tumor types (1.1 vs 11, P < .001) was consistently worse in those who received pATBs vs those who did not. Multivariate analyses confirmed that pATB therapy (HR, 3.4; 95% CI, 1.9-6.1; P < .001) and response to ICI therapy (HR, 8.2; 95% CI, 4.0-16.9; P < .001) were associated with OS independent of tumor site, disease burden, and performance status. Conclusions and Relevance: Despite being limited by sample size, geographic origin, and the lack of correlative analyses on patients' gut microbiota, this study suggests that pATB therapy but not cATB therapy is associated with a worse treatment response and OS in unselected patients treated with ICIs in routine clinical practice. Mechanistic studies are urgently required to investigate ATB-mediated alterations of gut microbiota as a determinant of poorer outcome following ICI treatment.