Citations

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

Male and female glioblastomas are biologically distinct, and improving outcomes may require sex-specific approaches to treatment.

PurposeDespite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype—growth before treatment and during each treatment to recurrence —has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK.Patients and MethodsFrom our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment.ResultsThere was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%).ConclusionDichotomizing the heterogeneity of GBMs into two populations—one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival—suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.

Objectives/HypothesisSarcomatoid carcinoma is a rare variant of squamous cell carcinoma of the head and neck. No consensus exists on its management. Our aim was to present our outcomes.Study DesignRetrospective study. Median follow‐up 45 months.MethodsThere were 38 patients with pathologically confirmed sarcomatoid carcinoma of the larynx treated at the Mayo Clinic from 1990 to 2014. Statistical analysis of overall survival (OS), progression‐free survival (PFS), and local control (LC) were conducted using the Kaplan‐Meier method.ResultsThe majority of patients were elderly males (92%) with a smoking history (74%) presenting with early‐stage disease (71%). Surgery alone was the primary treatment in 27 patients (71%). Nine patients (25%) were treated with adjuvant radiation due to initial stage or high‐risk pathologic features. Median radiation dose to the primary/surgical bed was 65 Gy (range, 60.3–75.0 Gy). A total of 15 patients (39%) had tumor recurrence, majority being local (n = 12). Sixty percent (n = 9) had multiple local recurrences. Five‐year OS, PFS, and LC were 63%, 46%, and 72%, respectively. Subgroup analysis by stage I versus higher stages (II–IV) showed an OS of 80% versus 43% (P = .030), PFS of 65% versus 18% (P = .003), and LC of 84% versus 57% (P = .039).ConclusionsSarcomatoid carcinoma of the larynx is rare, and frequently presents at an early stage in older men with history of smoking. Based on our outcomes and patterns of failure, it appears early‐stage tumors are treated appropriately with single‐modality therapy, whereas more advanced tumors require multimodality therapy. Validation in a larger cohort is warranted.Level of Evidence4. Laryngoscope, 128:373–377, 2018

AbstractBackgroundUnilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low‐volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced‐stage oropharyngeal cancer undergoing unilateral RT.MethodsThirty‐seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected.ResultsAt median follow‐up of 32 months, 3‐year locoregional control, contralateral regional failure, distant metastasis‐free survival, and disease‐free survival were 96%, 0%, 7%, and 93%, respectively.ConclusionLow rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

Purpose: To report the outcomes of patients with favorable risk oropharyngeal cancer that underwent adjuvant radiation therapy with omission of the primary site from the clinical target volume (CTV). Material/Methods: A retrospective study of 40 patients treated with transoral surgery (TOS) followed by neck only radiation using intensity modulated radiation therapy (IMRT) with exclusion of the primary site. For all patients, a CTV of the primary surgical bed was contoured to obtain the estimated incidental dose to the primary site. Results: Median follow-up was 51 months (range, 13-155 months). The median radiation therapy (RT) dose to the neck was 6000 cGy (range, 5400-6400 cGy). The mean incidental dose to the primary tonsillar site was 4320 cGy (SD ± 480 cGy) and to the primary base of tongue site was 4060 cGy (SD ± 420 cGy). There were no local failures and only 1 regional failure, resulting in 97.5% locoregional control rate at 4 years. Two patients developed distant metastases, without evidence of locoregional recurrence, for a 4-year overall survival rate of 97%. Conclusions: Our analysis suggests that mucosal sparing RT after TOS in favorable risk oropharyngeal cancer patients may provide comparable oncologic and improved functional outcomes compared to conventional treatment in selected patients.