Radiation, Immune Checkpoint Blockade and the Abscopal Effect: A Critical Review on Timing, Dose and Fractionation

The combination of radiation and immunotherapy is currently an exciting avenue of pre-clinical and clinical investigation. The synergy between these two treatment modalities has the potential to expand the role of radiation from a purely local therapy, to a role in advanced and metastatic disease. Tumor regression outside of the irradiated field, known as the abscopal effect, is a recognized phenomenon mediated by lymphocytes and enhanced by checkpoint blockade. In this review, we summarize the known mechanistic data behind the immunostimulatory effects of radiation and how this is enhanced by immunotherapy. We also provide pre-clinical data supporting specific radiation timing and optimal dose/fractionation for induction of a robust anti-tumor immune response with or without checkpoint blockade. Importantly, these data are placed in a larger context of understanding T-cell exhaustion and the impact of immunotherapy on this phenotype. We also include relevant pre-clinical studies done in non-tumor systems. We discuss the published clinical trials and briefly summarize salient case reports evaluating the abscopal effect. Much of the data discussed here remains at the preliminary stage, and a number of interesting avenues of research remain under investigation

Germ Cell Tumors in Undescended Testis-Prognostic Factors and Treatment Outcome

and the incidence has been increasing The purpose of this retrospective review of patients with germ cell tumor in undescended testis is to study the clinicopathological features and disease outcome for this relatively rare but intriguing problem. PATIENTS AND METHODS Over a 22-year period from January 1975 to December 1997, 270 patients with the histologic diagnosis of germ cell tumor of the testis (147 seminoma and 123 non-seminoma) were seen at King Faisal Specialist Hospital and Research Centre (KFSH & RC), which is a national tertiary care cancer centre in Saudi Arabia. Out of the 270 patients, 35 (13%) had germ cell tumor in undescended testis. All histologic materials were reviewed by pathologists at KFSH & RC at the time of initial referral. The pa- ABSTRACT The medical records of 270 patients with germ cell tumors of the testis (147 seminoma and 123 non-seminoma) seen at our institute between 1975-1997 were reviewed. Thirty-five (13%) patients had tumors in undescended testis, seminoma in 28 and 7 patients had non-seminoma. The mean age at diagnosis was 34 years. Orchiopexy was performed in only 4 patients. The involved testis was in the scrotum in the 4 patients who had orchiopexy, in the inguinal canal in 15 and in the lower abdomen in 16. Pain and palpable mass were the most common presenting symptoms. Using the modified Royal Marsden Hospital staging system, the stage at diagnosis was I in 14 patients, II in 18 and IV in 3. Orchiectomy was carried out in 26 patients, open biopsy in 3 and fine needle aspiration in 6. For patients with seminoma, 14 patients received external radiation (XRT) only, 7 chemotherapy, and combined XRT and chemotherapy in 6 patients. One patient had orchiectomy only. Patients with non-seminoma were treated with chemotherapy. Complete response was achieved in 84% of the seminoma cases. At a median follow up of 52 months (range 2 months-19.5 years), the 5-year overall actuarial survival rate for patients with seminoma was 85% compared to 68% in patients with non-seminoma. Univariate and multivariate analyses for survival were done for the 28 patients with seminoma. Early stage and complete response to treatment were associated with significant high survival rate in univariate analysis. None of the above were significant on multivariate analysis. Conclusion: Patients with undescended testes have a higher risk for developing seminoma than non-seminoma. Treatment results of germ cell tumors in undescended testis are equivalent to those in normally located testis

Comparison of Lhermitte’s Sign (LS) vs non-LS patients with VMAT radiation to the head and neck, without chemotherapy ^*.

<p>* figures are represented as mean ± standard deviation, unless noted otherwise</p><p>Comparison of Lhermitte’s Sign (LS) vs non-LS patients with VMAT radiation to the head and neck, without chemotherapy ^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139448#t002fn001" target="_blank">*</a>}.</p

All patients with VMAT radiation treatment to the head and neck, without chemotherapy.

<p>* Values are represented as mean ± standard deviation, unless noted otherwise</p><p>All patients with VMAT radiation treatment to the head and neck, without chemotherapy.</p

Lhermitte’s Sign following VMAT-Based Head and Neck Radiation-Insights into Mechanism - Fig 1

<p>(A) The dose gradient (Gy) between left and right quadrants was calculated in LS (green triangles), and non-LS (purple circles) with respect to cervical spinal level. * A repeated-measures ANOVA (p = 0.026) demonstrate that the LS group means were overall different from those of the non-LS group. (B) The dose gradient (Gy) between anterior and posterior quadrants was calculated in LS (green triangles), and non-LS (purple circles) with respect to cervical spinal level. A repeated-measures ANOVA (p = 0.434) was not significant.</p