Prakash Peddi

Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment

Histiocytic sarcoma (HS) is an extremely rare non‐Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary HS. Deriving conclusions from previously reported cases of HS arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72‐year‐old man with a diagnosis of chronic myeloid leukemia (CML), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of HS. The liver mass showed a retained BCR‐ABL1 translocation suggesting clonality between the CML and HS. As seen in our case and other reported cases of HS derived secondarily, the concurrent expression of immunoglobulin heavy (IGH)‐/light‐chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself.

Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment

Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by tumor cell or other immune cells on the immune system, promoting antitumoral immune response. To date, two programmed death-1 inhibitors, namely nivolumab and pembrolizumab, have received the US Food and Drug Administration approval for the treatment of advanced non-small-cell lung cancer that failed platinum-based chemotherapy. This manuscript provides a brief overview of the pathophysiology of cancer immune evasion, summarizes pertinent data on completed and ongoing clinical trials involving checkpoint inhibitors, discusses the different strategies to optimize their function, and outlines various challenges that are faced in this promising yet evolving field.

Regression of a glioblastoma multiforme: spontaneous versus a potential antineoplastic effect of dexamethasone and levetiracetam

Patients with grade IV astrocytoma or glioblastoma multiforme (GBM) have a median survival of <12 months, increased to 14.6 months by maximal safe resection with radiation and temozolamide. In the absence of chemotherapy, radiotherapy or chemoradiotherapy, spontaneous regression of GBM or regression while only being on dexamethasone (DEX) and levetiracetam (LEV) have seldom been reported. Here, we present a case of a patient who had significant regression of the GBM with DEX and LEV alone. In this study, we hypothesise a plausible antineoplastic role of DEX and or LEV in GBM and highlight molecular, preclinical and clinical studies supporting this role.

Tolosa-Hunt Syndrome in Double-Hit Lymphoma

Tolosa-Hunt syndrome (THS) is a painful condition characterized by hemicranial pain, retroorbital pain, loss of vision, oculomotor nerve paralysis, and sensory loss in distribution of ophthalmic and maxillary division of trigeminal nerve. Lymphomas rarely involve cavernous sinus and simulate Tolosa-Hunt syndrome. Here we present a first case of double-hit B cell lymphoma (DHL) relapsing and masquerading as Tolosa-Hunt syndrome. The neurological findings were explained by a lymphomatous infiltration of the right Gasserian ganglion which preceded systemic relapse. As part of this report, the diagnostic criteria for Tolosa-Hunt syndrome and double-hit lymphoma are reviewed and updated treatment recommendations are presented.

Successful treatment of first and second recurrence of acute lymphoblastic leukemia after related allogeneic bone marrow transplant at unusual sites using single-dose vincristine followed by interferon-α2b and granulocyte-macrophage colony-stimulating factor

Successful treatment of first and second recurrence of acute lymphoblastic leukemia after related allogeneic bone marrow transplant at unusual sites using singledose vincristine followed by interferon-α2b and granulocyte-macrophage colony-stimulating factor Leonid Volodin, Prakash Peddi, Amol Takalkar, Jill M. Comeau, Jaime L. Shahan & Gerhard C. Hildebrandt a Louisiana State University Health Sciences Center – Shreveport, Shreveport, LA, USA b Blood and Marrow Transplantation in the Department of Medicine, Stanford School of Medicine, CA, USA c PET Imaging Center, Biomedical Research Foundation of Northwest Louisiana; Department of Radiology, Nuclear Medicine Section, Louisiana State University Health Sciences Center – Shreveport, Shreveport, LA, USA Published online: 01 Jun 2015.

Exceptional response to cetuximab monotherapy in a patient with metastatic oropharyngeal squamous cell carcinoma: A molecular insight

Background Metastatic head and neck squamous cell carcinoma (HNSCC) carries a very poor prognosis. A better understanding of the molecular driver of the disease and the identification of biomarkers of response remain paramount for an effective personalized therapy. Case report We report an original case of a 56-year-old patient diagnosed with metastatic HNSCC to both kidneys, who experienced a long-lasting complete response to a single-agent cetuximab, a monoclonal antibody-targeting EGFR. Comprehensive multiplatform biomarker analysis of the tumor revealed the presence of phosphatidyl-inositol 3 kinase mutation, EGFR overexpression, and the absence of PD-1/PD-L1 expression. Since PI3K, a downstream effector of EGFR, is activated, the tumor regression may have occurred mainly through a cetuximab-induced immune-mediated response, rather than EGFR signal blockade. It is plausible that this effect was enhanced by the lack of PD-1 and PD-L1 expression. Conclusion Our case proposes that the absence of PD-1 and PD-L1 expression in conjunction with EGFR overexpression may correlate with better response to cetuximab in HNSCC. This hypothesis needs to be examined through a large clinical trial.

Outcomes in real-world practice are different than cooperative trial for elderly patients with early breast cancer treated with adjuvant radiation therapy

Background: The Cancer and Leukemia Group B 9,343 demonstrated that postoperative radiation can be safely omitted in women ≥70 years who underwent breast‐conserving therapy for clinical stage I (T1N0M0) estrogen receptor positive breast cancer treated with antihormonal therapy. Whether such results are observed in real‐world population is unknown. In this hospital‐based data, we report the survival outcomes of patients who received adjuvant radiation therapy versus those who did not. Methods: Using the National Cancer Data Base, we evaluated a cohort of 47,358 women with newly diagnosed breast cancer between 2004 and 2011 who underwent a lumpectomy and antihormonal therapy with the following criteria: age ≥70 years, clinical stage I, estrogen receptor positive, and negative margins. Patients were stratified into 2 groups: (1) radiation therapy and (2) no radiation therapy. Propensity score matching was used to compensate for differences in demographic and clinical characteristics of the patients. Univariate and multivariable survival analysis were employed to determine factors associated with overall survival. Results: The 5‐year overall survival after propensity score matching was 87.2% for radiation therapy and 79.4% for no radiation therapy (P < .0001). The median survival time was 113.7 months for radiation therapy and 105.2 months for no radiation therapy. After adjusting for sociodemographic and clinical factors, the risk of overall deaths was significantly higher for those not receiving radiation therapy (hazard ratio = 1.66; 95% confidence interval, 1.54–1.79). Other significant adjusted predictors (P < .05) of poor overall survival were, advanced age, comprehensive community cancer program, facility location, poorly differentiated tumor, and high comorbidity index. Conclusion: Patients who received radiation therapy had better survival outcomes than those who did not, revealing discordance between results of randomized trials and real‐world setting.

Radiation Therapy for Positive Surgical Margins in Women ≥70 Years with Stage I, Estrogen Receptor-positive Breast Cancer

Background/Aim: A re-excision for positive margin(s) following a lumpectomy for invasive breast cancer is a standard recommendation. However, for elderly women with stage I estrogen receptor-positive (ER+) tumors, who may be at higher surgical risk, whether radiation therapy without re-excision will be adequate is not known. Patients and Methods: We evaluated a cohort of 53,950 women aged ≥70 years with Stage I, ER+ breast cancer who had lumpectomy and anti-hormone therapy diagnosed between 2004 and 2011 in the National Cancer Data Base. Patients were divided into four groups: 1) negative margins without radiation (XRT), 2) negative margins with XRT, 3) positive margins without XRT, and 4) positive margins with XRT. Clinicopathological and sociodemographic variables were compared among these groups. Univariable and multivariable analysis were employed. Results: The 5-year overall survival (OS) rates for the groups were as follows: 1) negative margins without radiation (XRT); 77.1%, 2) negative margins with XRT; 90.0%, 3) positive margins without XRT; 62.9%, and 4) positive margins with XRT; 86.8% (p<0.0001). Significant predictors (p<0.01) of OS include treatment groups, age, income status, facility type, facility location, tumor size, tumor grade, and comorbidities. Conclusion: Radiation therapy for positive surgical margins without re-excision may be a viable option for elderly women with stage I, ER+ tumor treated with lumpectomy and hormonal therapy.

Recurrent Malignant Melanoma Presenting as Isolated Pleural Metastases in a Patient with Chronic Lymphocytic Leukemia

Isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma. We report an unusual case of a patient with chronic lymphocytic leukemia (CLL) and recurrent pleural effusions. The pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of CLL. However, chemotherapy with pentostatin, cyclophosphamide, and rituximab did not result in any meaningful clinical response. A video-assisted thoracoscopic surgery and biopsy of the affected nodular parietal layer of the pleura were consistent with malignant melanoma. Our case underlines the importance of having a suspicion for secondary causes of effusion in patients with CLL. We briefly discuss the mechanisms of an increased incidence of secondary cancers in CLL and the diagnosis of isolated pleural metastases in malignant melanoma.

Reversal of isolated 20q deletion with vitamin B12 replacement in a patient with pernicious anaemia

Severe vitamin B12 deficiency is well known to cause morphological alterations in bone marrow. In rare instances, these myelodysplastic and megaloblastic changes can coexist with cytogenetic abnormalities. Here, we report a case of a 38-year-old African-American woman with pernicious anaemia, who was found to have an isolated 20q deletion and which resolved after vitamin B12 replacement. We also discuss various mechanisms in which vitamin B12 deficiency can lead to chromosomal abnormalities. A literature review is also performed to evaluate various other chromosomal aberrations associated with B12 deficiency.