Cheryl Alexander

Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes

BackgroundThe immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival.MethodsALC values were collected from patient records ≥ 2 years before, during or after primary treatment for high-grade serous ovarian cancer (HGSC). Lymphocyte subsets were assessed in peripheral blood by flow cytometry. CD8+ and CD20+ TIL were assessed by immunohistochemistry.ResultsOverall, patients had normal ALC values two or more years prior to diagnosis of HGSC. These values were not predictive of disease severity or survival upon subsequent development of HGSC. Rather, ALC declined upon development of HGSC in proportion to disease burden. This decline involved all lymphocyte subsets. ALC increased following surgery, remained stable during chemotherapy, but rarely recovered to pre-diagnostic levels. ALC values recorded at diagnosis did not correlate with CD8+ or CD20+ TIL but were associated with progression-free survival.ConclusionsPatients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC.

Effect of radiotherapy boost and hypofractionation on outcomes in ductal carcinoma in situ.

Boost radiotherapy (RT) improves outcomes for patients with invasive breast cancer, but whether this is applicable to patients with pure ductal carcinoma in situ (DCIS) is unclear. This study examined outcomes from whole breast RT, with or without a boost, and the impact of different dose‐fractionation schedules in a population‐based cohort of women with pure DCIS treated with breast‐conserving surgery (BCS).

Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

PURPOSE To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). METHODS AND MATERIALS Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. RESULTS Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age>60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). CONCLUSIONS This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL-leg is a more aggressive disease; the excellent results in the rituximab group suggest it has an important role in management.

Treatment and Outcomes of Primary Breast Lymphoma

PURPOSE To evaluate treatment and outcomes in a population-based cohort of patients diagnosed with primary breast lymphoma. METHODS AND MATERIALS Prognostic factors, management, and outcomes (local control, lymphoma-specific survival, and overall survival) were analyzed for all patients diagnosed with limited-stage, primary breast non-Hodgkin lymphoma (n = 50) diagnosed in British Columbia between 1981 and 2009. RESULTS The median follow-up was 3.5 years; 64% presented with a breast mass. Histologic subtypes were indolent (n = 16 [32%]) or aggressive (n = 34 [68%]). Of those with indolent lymphoma, 81% had stage I, and 19% had stage II disease; 13% received no initial treatment; 75% received radiotherapy (RT) alone. One (6%) patient received surgical resection alone, and 1 (6%) patient received surgical resection in addition to RT. Of those with aggressive lymphoma, 62% had stage I and 38% had stage II disease; 3% received no initial treatment; 6%, RT alone; 38%, chemotherapy only; 41%, chemotherapy and RT; 9%, surgical resection alone; and 3%, surgical resection in addition to chemotherapy and RT. In patients with indolent and aggressive disease, 5-year local control estimates were 92% and 96%, lymphoma-specific survivals were 91% and 71%, and overall survivals were 75% and 54%, respectively. On univariate analysis, stage (I vs. II) (P = .006) and RT use (P = .032) were statistically significant predictors of improved overall survival in patients with indolent breast lymphoma. Combined chemoradiation was associated with a trend for improved overall survival (P = .061) in patients with aggressive disease. There were 4 cases of central nervous system relapse, all occurred in subjects with aggressive primary breast lymphoma. CONCLUSIONS Patients with indolent breast lymphoma were most frequently treated with RT alone and achieved high rates of local control and survival. Patients with aggressive histology most often treated with chemotherapy, alone or combined with RT, had excellent local control but lower survival compared with indolent disease. Improved systemic therapies are needed to improve outcomes for patients with aggressive breast lymphoma.

Intratumoral Immune Responses Can Distinguish New Primary and True Recurrence Types of Ipsilateral Breast Tumor Recurrences (IBTR)

Ipsilateral breast tumor recurrence (IBTR) is an increasingly common clinical challenge. IBTRs include True Recurrences (TR; persistent disease) and New Primaries (NP; de novo tumors), but discrimination between these is difficult. We assessed tumor infiltrating leukocytes (TIL) as biomarkers for distinguishing these types of IBTR using primary tumors and matched IBTRs from 24 breast cancer patients, half of which were identified as putative TRs and half as NPs using a previously reported clinical algorithm. Intratumoral lymphocyte populations (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) and macrophages (CD68) were quantified by immunohistochemistry in each tumor. Compared to matched primaries, TRs showed significant trends towards increased CD3+ and CD8+ TIL, while these populations were often diminished in NPs. Comparison of IBTRs showed that TRs had significantly higher levels of CD3+ (P = 0.0136), CD8+ (P = 0.0092), and CD25+ (P = 0.0159) TIL than NPs. We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.