Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8+ T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8+ T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8+ T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.

Hypofractionated Adjuvant Radiation Therapy Is Effective for Patients With Lymph Node-Positive Breast Cancer: A Population-Based Analysis.

PURPOSE: This study evaluated long-term, population-based, breast cancer-specific outcomes in patients treated with radiation therapy (RT) to the breast/chest wall plus regional nodes using hypofractionated (HF) (40-42.5 Gy/16 fractions) versus conventionally fractionated (CF) regimens (50-50.4 Gy/25-28 fractions). METHODS AND MATERIALS: A prospective provincial database was used to identify patients with lymph node-positive breast cancer treated with curative-intent breast/chest wall + regional nodal RT from 1998 to 2010. The effect of RT fractionation on locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) was assessed for the entire cohort and for high-risk subgroups: grade 3, ER-/HER2-, HER2+, and ≥4 positive nodes. Multivariable analysis and 2:1 case-match comparison of HF versus CF were also performed. RESULTS: A total of 5487 patients met the inclusion criteria (4006 HF and 1481 CF). Median age was 55 years, and median follow-up was 12.7 years. On multivariable analysis, no statistically significant differences were identified in 10-year LRRFS (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.59-1.27; P = .46), DRFS (HR 0.90; 95% CI, 0.76-1.06; P = .19), or BCSS (HR 0.92; 95% CI, 0.76-1.10; P = .36) between the HF and CF cohorts. There was no statistical difference in breast cancer-specific outcomes in the high-risk subgroups. On analysis of 2962 HF cases matched to 1481 CF controls, no statistical difference was observed in LRRFS (HR 0.98; 95% CI, 0.71-1.33; P = .87), DRFS (HR 0.97; 95% CI, 0.85-1.11; P = .68), or BCSS (HR 1.00; 95% CI, 0.87-1.16; P = .92). CONCLUSIONS: This large, population-based analysis with long-term follow-up after locoregional RT demonstrated that modest HF provides similar breast cancer-specific outcomes compared with CF. HF is an effective option for patients with stage I to III breast cancer receiving nodal RT.

Anemia, leukocytosis and thrombocytosis as prognostic factors in patients with cervical cancer treated with radical chemoradiotherapy: A retrospective cohort study.

INTRODUCTION: Anemia has long been associated with poor prognosis in patients with cervical cancer. Recently, additional hematologic parameters have emerged as potential indicators of worse outcome in this patient group. In a cohort of cervical cancer patients treated with chemoradiotherapy (CRT) and brachytherapy, we report on the prognostic significance of hematologic parameters including anemia, leukocytosis, neutrophil to lymphocyte ratio (NLR), and thrombocytosis, the effect of combining anemia with other hematologic parameters, and the effect of changes in hemoglobin levels during treatment. MATERIALS AND METHODS: Two-hundred fifty-seven cervical cancer patients were retrospectively identified from a single cancer institution's database. Hematologic parameters were categorized as: anemia (hemoglobin ≤115 g/L), leukocytosis (white blood cell count >10 × 109/L), thrombocytosis (platelets >400 × 109/L), and NLR (ratio >5). The association between clinical factors and hematologic parameters on progression-free survival (PFS) and overall survival (OS) were assessed at 5 years. RESULTS: At 5 years, both pre-treatment anemia (PFS: 60% vs 34%, p < 0.0001; OS: 68% vs 41%, p < 0.0001) and on-treatment anemia (PFS: 62% vs 40%, p < 0.0001; OS: 70% vs 48%, p < 0.0001) were significantly associated with worse survival. This adverse effect on 5-year PFS and OS was increased in patients with both pre-treatment anemia and leukocytosis (PFS: 72% vs 42%, p < 0.0001; OS: 68% vs 37%, p < 0.0001) and pre-treatment anemia and elevated NLR (PFS: 61% vs 30%, p < 0.0001; OS: 68% vs 37%, p < 0.0001). Five-year PFS (50% vs 31%) and OS (60% vs 36%) was better in patients whose pre-treatment anemia improved to normal hemoglobin levels on treatment vs those patients who were anemic both pre- and on-treatment. CONCLUSION: Pre-treatment and on-treatment anemia were significant, independent predictors of worse PFS and OS. Anemia and other hematologic parameters remain prognostic markers for cervical cancer patients. Improvement in PFS and OS was seen in patients with normalization of hemoglobin.

Implementation and validation of a combined MRI-CT-based cervical cancer brachytherapy program using existing infrastructure.

PURPOSE: To describe the implementation of an MRI-CT-based cervical cancer brachytherapy (BT) program using existing infrastructure. To evaluate its impact on treatment planning. METHODS AND MATERIALS: A step-wise method was used to design and implement three-dimensional-based planning. Prospective risk analysis was used to create a process map and planning protocol. To evaluate the program, charts of cervical cancer patients treated curatively between January 2013 and December 2014, with at least one MRI during BT planning, were reviewed. Dosimetric comparisons were made between prescription point used and that of the traditional Point A and between MRI-planned treatments and CT-planned treatments. They were evaluated for differences between plans as well as adherence to Groupe Européen de Curiethérapie-European Society for Radiotherapy & Oncology (GEC-ESTRO) recommendations for high-risk clinical target volume coverage and organs-at-risk constraints. RESULTS: Implementation of the MRI-CT planning program occurred using existing infrastructure. Key to the implementation was communication between departments and the use of a process map to document the workflow. Eighty percent of treatments were prescribed to a point other than Point A, there were no major differences between the MRI-planned and CT-planned (with MRI guidance) treatments, and GEC-ESTRO recommendations were met for target coverage and organs at risk dose constraints. CONCLUSIONS: It was feasible to implement an MRI-CT-based cervical cancer BT planning program using existing infrastructure and that resulting plans meet GEC-ESTRO recommendations.

Hypofractionated whole breast radiotherapy: current perspectives.

Adjuvant radiotherapy (RT) is an important part of breast cancer management but the dose and fractionation schedules used are variable. A total of 50 Gy in 25 daily fractions delivered over 5 weeks is often considered the "standard" adjuvant RT prescription. Hypofractionated regimes such as 42.5 Gy in 16 daily fractions or 40 Gy in 15 daily fractions following breast-conserving surgery have proven to be equally effective and achieve similar or better cosmetic and normal tissue outcomes for both invasive and in situ diseases and when treating the regional nodes. Hypofractionation is more convenient for patients and less costly. However, certain patients at higher risk of RT late effects may benefit from a less intense, even more extended fractionation schedule. This review describes the indications for whole breast hypofractionated adjuvant RT for patients with breast cancer following breast-conserving surgery and proposes that hypofractionation should be the new "standard" for adjuvant breast cancer RT.