Quantitative lymph node burden as a 'very-high-risk' factor identifying head and neck cancer patients benefiting from postoperative chemoradiation.

Background: Adjuvant chemoradiation (CRT) is standard for head and neck squamous cell carcinoma (HNSCC) patients with positive margins or extranodal extension (ENE) following surgery. However, emerging evidence suggests the number of positive lymph nodes (LNs) is the dominant determinant of survival in non-oropharyngeal HNSCC and thus may better identify those benefiting from treatment intensification. Patients and methods: Patients from the National Cancer Database diagnosed with non-oropharyngeal HNSCC (oral cavity, larynx, hypopharynx) between 2004 and 2014 and undergoing surgical resection, neck dissection, and postoperative radiotherapy (RT) were included. Multivariable regression with first-order interaction terms was used to model the interaction between postoperative CRT and continuous number of positive LNs with respect to overall survival. Results: In total, 7144 patients met inclusion criteria. In multivariable analysis, increasing number of positive LNs was associated with both increasing mortality (P < 0.001) and increasing benefit from postoperative CRT versus RT alone (interaction P < 0.001). While there was no benefit from postoperative CRT in patients with 0-2 LN+ [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.86-1.07, P = 0.47], increased benefit was seen in those with 3-5 LN+ (HR 0.84, 95% CI 0.70-1.00, P = 0.05) and those with ≥6 LN+ (HR 0.65, 95% CI 0.51-0.82, P < 0.001) in multivariable models. By contrast, margin status and ENE did not reliably identify patients benefitting from postoperative CRT based on statistical tests of interaction. Even in patients with ENE, positive margins, or both, only those with ≥6 LN+ had improved survival with postoperative CRT. Conclusion: Increasing metastatic nodal burden was associated with increased benefit from CRT compared with RT alone, surpassing conventional high-risk factors in identifying patients benefiting from CRT. Stratification by metastatic LN number may characterize a very-high-risk patient cohort best suited for treatment intensification.

Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up.

BACKGROUND: There has been a recent proposal to change the grading system of prostate cancer into a five-tier grade grouping system. The prognostic impact of this has been demonstrated in regards only to biochemical recurrence-free survival (bRFS) with short follow-up (3 years). METHODS: Between 1990 and 2013, 847 consecutive men were treated with definitive external beam radiation therapy at a single academic center. To validate the new grade grouping system, bRFS, distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS) were calculated. Adjusted Kaplan-Meier and multivariable Cox regression analyses were performed to assess the independent impact of the new grade grouping system. Discriminatory analyses were performed to compare the commonly used three-tier Gleason score system (6, 7 and 8-10) to the new system. RESULTS: The median follow-up of our cohort was 88 months. The 5-grade groups independently validated differing risks of bRFS (group 1 as reference; adjusted hazard ratio (aHR) 1.35, 2.16, 1.79 and 3.84 for groups 2-5, respectively). Furthermore, a clear stratification was demonstrated for DMFS (aHR 2.03, 3.18, 3.62 and 13.77 for groups 2-5, respectively) and PCSS (aHR 3.00, 5.32, 6.02 and 39.02 for groups 2-5, respectively). The 5-grade group system had improved prognostic discrimination for all end points compared with the commonly used three-tiered system (that is, Gleason score 6, 7 and 8-10). CONCLUSIONS: In a large independent radiotherapy cohort with long-term follow-up, we have validated the bRFS benefit of the proposed five-tier grade grouping system. Furthermore, we have demonstrated that the system is highly prognostic for DMFS and PCSS. Grade group 5 had markedly worse outcomes for all end points, and future work is necessary to improve outcomes in these patients.

Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease.

BACKGROUND: Magnetic resonance imaging (MRI) is not routinely performed before initiating radium-223 to document spinal epidural disease. However, radium-223 decays to form α-particles with very short path lengths that may not reach the epidural space. Herein, we investigate the impact of baseline spinal epidural disease on metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223. METHODS: Between October 2013 to December 2014, 41 consecutive mCRPC patients at a large tertiary cancer center were prescribed radium-223 as part of standard of care. 29% of patients had pre-treatment epidural disease (posMRI), 27% had no epidural disease (negMRI), and 44% did not have a baseline MRI (noMRI). All patients had post-treatment spinal imaging. Actuarial survival times were calculated for overall survival (OS), spinal axis radiographic progression-free survival (spinePFS) and epidural progression-free survival (epiPFS) from time of first radium-223 treatment. RESULTS: For patients with posMRI (n=12), noMRI (n=18) and negMRI (n=11) cumulative rates of development or worsening of epidural disease and/or high-grade cord compression at time of last follow-up were 83%, 44% and 9%, respectively (P=0.001). For the posMRI, noMRI and negMRI groups the median OS was 6.3 months, 12.6 months and not reached (P=0.01), the median spinePFS was 3.2 months, 4.8 months and not reached (P=0.01), and the median epiPFS was 3.2 months, 10.4 months and not reached (P=0.001). Completing less than six cycles of radium-223 was significantly associated with worse OS (P<0.0001), spinePFS (P=0.007) and epiPFS (P=0.01). Greater than or equal to twenty osseous lesions pre-treatment was significantly associated with worse spinePFS (P=0.001) and epiPFS (P=0.03). CONCLUSIONS: In a heavily pre-treated small cohort, patients with baseline epidural disease frequently progressed to spinal cord compression and early cessation of radium-223 therapy. Studies are needed to determine the optimal timing of radium-223 with other mCRPC therapies given the predilection for epidural disease and treatment failure after multiple prior lines of mCRPC therapy.