Complete Pathologic Response Following Multimodality Therapy for a Recurrent, High-Grade Phyllodes Tumor

Introduction: Phyllodes tumor is a rare mesenchymal tumor of the breast for which surgical resection is the primary therapy. Despite adequate surgical resection, local recurrence rates of up to 40% are observed in patients with high-grade tumors. The role of adjuvant radiation therapy and chemotherapy for phyllodes tumor to improve local and systemic control is not well established. However, several small studies have shown improvements in local control rates with adjuvant radiation therapy. The management of aggressive local phyllodes tumor recurrences can be a clinical challenge and multimodality therapy should be considered in these cases for optimal results.Case presentation: We present the case of a high-grade phyllodes tumor that recurred in the radiation field after adjuvant radiation therapy. The patient was treated with neoadjuvant hyperfractionated, accelerated radiotherapy in combination with hyperthermia and chemotherapy followed by radical surgical resection. A completed pathologic response was observed.Conclusion: This multimodality approach may be a successful treatment algorithm for high-grade tumors that reoccur in a prior radiation field

Pathologic Prognostic Factors in Endometrial Carcinoma (Other Than Tumor Type and Grade)

Although endometrial carcinoma (EC) is generally considered to have a good prognosis, over 20% of women with EC die of their disease, with a projected increase in both incidence and mortality over the next few decades. The aim of accurate prognostication is to ensure that patients receive optimal treatment and are neither overtreated nor undertreated, thereby improving patient outcomes overall. Patients with EC can be categorized into prognostic risk groups based on clinicopathologic findings. Other than tumor type and grade, groupings and recommended management algorithms may take into account age, body mass index, stage, and presence of lymphovascular space invasion. The molecular classification of EC that has emerged from the Cancer Genome Atlas (TCGA) study provides additional, potentially superior, prognostic information to traditional histologic typing and grading. This classifier does not, however, replace clinicopathologic risk assessment based on parameters other than histotype and grade. It is envisaged that molecular and clinicopathologic prognostic grouping systems will work better together than either alone. Thus, while tumor typing and grading may be superseded by a classification based on underlying genomic abnormalities, accurate assessment of other pathologic parameters will continue to be key to patient management. These include those factors related to staging, such as depth of myometrial invasion, cervical, vaginal, serosal surface, adnexal and parametrial invasion, and those independent of stage such as lymphovascular space invasion. Other prognostic parameters will also be discussed. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project

Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients

Pathologic Findings at Risk-Reducing Salpingo-Oophorectomy: Primary Results From Gynecologic Oncology Group Trial GOG-0199

Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Excision or Observation: The Dilemma of Managing High-Risk Breast Lesions.

There is an enduring dilemma on the appropriate management of high-risk breast lesions; is surgical excision always warranted or can conservative management be utilized? We present cases of high-risk breast lesions diagnosed at core needle biopsy at our institution along with relevant factors to consider for appropriate management. We conclude that a nuanced approach is warranted over the broad stroke approach of surgical excision of all high-risk breast lesions

Breast magnetic resonance imaging (MRI) surveillance in breast cancer survivors

Purpose: As the breast cancer survivor population increases, the topic of screening these women for recurrences is increasingly relevant. In our institution, we use both breast MRI and mammography in the surveillance of breast cancer survivors, although little data exists on the use of MRI in this setting. We present a retrospective analysis of our experience and compare the sensitivity and specificity of MRI vs. mammography in this setting. Methods: We identified women under 65 with a history of breast cancer and at least one follow-up MRI performed along with a mammogram done within 6 months of the MRI. We compared the outcomes of MRI and mammography in terms of biopsies performed as well as in detection of new cancers. Results: Of 617 charts reviewed, 249 patients met inclusion criteria, with 571 paired MRI/mammogram results. There were 27 biopsies performed due to MRI findings alone, 10 done due to mammographic findings alone, and 15 done based on abnormalities seen on both imaging modalities. There were 8 malignancies identified based on an abnormal MRI, 3 detected on both MRI and mammography, and none identified via mammography alone. Overall, MRI had a sensitivity of 84.6% (the 95% CI 54.6-98.1) and a specificity of 95.3% (the 95% CI 93.3-96.9); mammography a sensitivity of 23.1% (the 95% CI 5.0-53.8), and a specificity of 96.4% (the 95% CI 94.5-97.8). Conclusions: Breast MRI is a useful surveillance modality in breast cancer survivors and may be more sensitive at detecting recurrences than mammography alone in this population