Tina Rizack

Management of hematological malignancies during pregnancy.

The management of hematological malignancies during pregnancy is a challenging endeavor, which not only requires technical skills and knowledge by the clinicians but also requires sound clinical judgment and compassion, keeping in mind the patient and family preferences and, ultimately, the wellbeing of the neonate. The incidence of hematological malignancies during pregnancy is rare, ranging from 1 in 1,000 to 1 in 10,000 deliveries, impeding the design and execution of large prospective studies. The purpose of this review is to evaluate the limited existing data and make useful suggestions in the management of acute and chronic leukemias, Hodgkin and non‐Hodgkin lymphomas, plasma cell myeloma, and other hematological malignancies, such as myelodysplastic syndromes and hairy cell leukemia, during pregnancy. Am. J. Hematol. 2009.

Medical Marijuana Use in Oncology: A Review

Importance Medicinal marijuana use is currently legal in 23 states and the District of Columbia. As more states approve marijuana use for medical indications, physicians will be asked by their patients for more information regarding the risks and benefits of use. This article reviews the history, adverse effects, and proposed mechanisms of action of marijuana and summarizes the available literature regarding symptom relief and therapeutic value in patients with cancer. Observations Marijuana in oncology may have potential for use as an antiemetic, for refractory cancer pain, and as an antitumor agent. However, much of the data are based on animal data, small trials, or are outdated. Conclusions and Relevance More research is needed in all areas related to the therapeutic use of marijuana in oncology.

A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study

Background A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod—a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses—combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6–12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. Results The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. Conclusions The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. Trial registration Clinicaltrials.gov, NCT 01666444.Background A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and gynecologic oncology group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. Results The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. Conclusions The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. Trial registration Clinicaltrials.gov, NCT 01666444.

Intracellular and extracellular rhomboid shaped crystalline inclusions in a case of IgG lambda restricted plasma cell myeloma: a case report and review of the literature

The presence of crystalline inclusions in plasma cell myeloma is a rare phenomenon and cases have been reported with rod, needle, and rectangular shaped crystals. Here, we present a case of IgG lambda restricted plasma cell myeloma with rhomboid shaped intracellular crystalline inclusions and extracellular crystal depositions in the bone marrow. Since rhomboid crystal depositions can be seen in other clinical conditions such as pseudogout, this case invites consideration of plasma cell myeloma in the differential diagnosis of patients with rhomboid crystalline deposition in the bone marrow and in sites/organs other than the bone marrow.

Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015

Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

survival of patients with squamous cell Malignancies of the Upper Urinary Tract

Background Carcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies. Methods We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 3.7 (95% CI 3.0–4.5) for SCC when compared to TCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (P = 0.84) and for patients with clear lymph nodes (P = 0.92). Conclusions SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.

Locally advanced vulvar cancer in elderly women: is chemoradiation beneficial?

Objectives:There is a higher incidence of invasive vulvar cancer in the elderly population. With multiple medical comorbidities, radiation with sensitizing chemotherapy in the elderly can be complicated, yet the risks and benefits of chemoradiation have not been studied in this population. We investigate whether elderly patients are more likely to die of intercurrent disease (ICD) or of treatment complications. Methods:A meta-analysis was performed to compare remission rates, death from ICD or treatment complications, and rates of surgery in elderly and nonelderly patients with vulvar cancer treated with chemoradiation. Data were searched in the Cochrane Review. Eligibility criteria included: woman with advanced primary squamous cell carcinoma of the vulva, women receiving preoperative or primary chemoradiation treatment with curative intent, and prospective studies that reported the necessary data of interest. Data collected included: age (elderly, defined as 65 years and above), stage, treatment, and mortality. Results:Seventy subjects were identified from 7 studies that met eligibility criteria. Seventy-eight percent (25/32) of patients younger than 65 years were without evidence of disease after treatment versus 66% (25/38) of patients aged 65 years and above (P=0.30). Three percent (1/32) of patients younger than 65 years of age died of ICD or treatment complications versus 11% (4/38) of patients 65 years and above (P=0.37). Conclusions:We noticed a trend demonstrating death from ICD or treatment complications was higher for elderly patients. Future research should focus on treatment with chemoradiation in the elderly population with regard to survival benefit, toxicity, and death from ICD or treatment complications.

Special Hematologic Issues in the Pregnant Patient

Evaluation and treatment of hematologic disorders in pregnancy requires an understanding of normal physiologic changes during pregnancy. Hematologic disorders may be caused by preexisting conditions, normal physiologic changes, or can be acquired. A multidisciplinary approach is often necessary for monitoring and treatment of both the mother and the fetus. In general, outcomes are good for both the mother and the fetus.

Predicting Breast Tumor Size for Pre‐operative Planning: Which Imaging Modality is Best?

We sought to compare breast tumor size predicted by imaging modality to the actual pathologic size in order to determine which imaging modality is best at estimating tumor size. We identified 261 patients with biopsy‐proven invasive ductal (IDC) and/or invasive lobular (ILC) carcinomas with documented tumor dimensions predicted by imaging and maximum dimensions determined by final pathology. Results of imaging‐predicted dimension were correlated with final pathological size. Spearman correlations were calculated and compared by Zous method and agreement was assessed by McNemars test. There was no significant difference (p > 0.05) between correlations of pathologic size by ultrasound (r = 0.71) and magnetic resonance imaging (MRI) (0.76). The correlations between MRI or ultrasound and pathologic size are significantly stronger than the correlations between mammography or clinical breast exam and pathologic size (p < 0.05). MRI and ultrasound are both strongly correlated with pathologic size overall and within grades in both IDC and ILC. The correlations between MRI or ultrasound and pathologic size are significantly better than the correlations between mammography or clinical breast exam and pathologic size (p < 0.05).

A phase I study of IV doxorubicin plus intraperitoneal (IP) paclitaxel and IV or IP cisplatin in endometrial cancer patients at high risk for peritoneal failure (GOG 9920): An NRG Oncology/Gynecologic Oncology Group study

OBJECTIVE To determine the maximum tolerated dose (MTD) of a modified paclitaxel/doxorubicin/cisplatin (TAP) regimen which incorporated intraperitoneal (IP) paclitaxel or IP paclitaxel/cisplatin in advanced endometrial cancer. METHODS Patients (pts) with FIGO (1998) Stage IIIA/IIIC with positive cytologic washings/ascites, adnexa, or serosa or Stage IV (intraperitoneal disease spread), histologically confirmed endometrial cancer were eligible. The study was designed as a phase I, 3+3 dose escalation study evaluating 5 dose levels (DL). All pts received cycles 1-2 with IV TAP, and cycles 3-6 with IV/IP therapy, on a 21day schedule. Adverse events were evaluated on cycles 3-4 for dose limiting toxicity (DLT) and dose escalation decisions. RESULTS Twenty-one pts were enrolled, of which 17 were evaluable for DLT. Most pts had Stage IV disease (76%) and serous/clear cell histology (59%). The MTD was determined to be DL 3 (cycles 3-6 including paclitaxel 90mg/m(2) IP, doxorubicin 45mg/m(2) IV, cisplatin 50mg/m(2)). Three DLT events occurred and were related to grades 3-4 metabolic toxicities. There was one grade 2 sensory neuropathy event and myelosupression was tolerable without the use of G-CSF. 88% of evaluable pts completed 6cycles of therapy. With a median follow-up of 22months, 46% of patients remain progression-free at 2years. CONCLUSION We described an IV/IP based modification of a standard TAP regimen in endometrial cancer. Based on the high rate of completing 6cycles of therapy, low rates of neuropathy, and promising PFS, further study of IP therapy in endometrial cancer is warranted.