Moffitt Comprehensive Cancer Center

Tampa, FL, United States

Moffitt Comprehensive Cancer Center

Tampa, FL, United States
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Hu K.S.,New York University | Mourad W.F.,Georgia Regents University | Lin W.,Mount Sinai at Beth Israel Medical Center | Jacobson A.S.,New York University | And 8 more authors.
Oral Oncology | Year: 2017

Purpose Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. Methods From 1998–2011, 60 patients were treated – N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. Results At median follow-up of 54 months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5 year rate of primary emergence in a non-oropharynx site was 3%. Conclusion This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes. © 2017 Elsevier Ltd


Pearman T.P.,Northwestern University | Beaumont J.L.,Northwestern University | Paul D.,National Comprehensive Cancer Network | Abernethy A.P.,Duke University | And 4 more authors.
Journal of Pain and Symptom Management | Year: 2013

Context: The Functional Assessment of Cancer Therapy-Head and Neck is a well-validated assessment of quality of life used with patients diagnosed with head and neck cancers (HCNs). The present study is an attempt to evaluate and modify this instrument as necessary in light of the recent regulatory guidelines from the Food and Drug Administration on the use of patient-reported outcomes in clinical trials. Objectives: Overall, the goal was to identify patients' highest priority cancer symptoms, compare these symptoms with those suggested by oncology experts, and construct a brief symptom index to assess these symptoms and categorize them as treatment-related, disease-related, or related to general function and well-being. Methods: Patients (N = 49) with advanced (Stages III and IV) HCNs were recruited from participating National Comprehensive Cancer Network institutions and community cancer support organizations in the Chicago area. Patients completed open-ended interviews and symptom checklists. Participating oncology physician experts also rated symptoms. Content validity was obtained by evaluating results alongside items in the Functional Assessment of Chronic Illness Therapy system. Eleven oncologists categorized symptoms in terms of importance and also whether the symptoms were primarily related to disease, treatment, or functional well-being. Results: HCN-related symptoms endorsed as high priority by both patients and oncology experts were selected for the new National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Head and Neck Cancer Symptom Index-22. The final version includes 22 items, which are broken down into disease-related symptoms, treatment side effects, or general function and well-being. The new scale has acceptable internal consistency (Cronbach's coefficient alpha = 0.86), content validity for use in chemotherapy trials of patients with advanced disease, and concurrent validity as demonstrated by moderate-to-strong correlations with the existing Functional Assessment of Chronic Illness Therapy measure. Conclusion: The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Head and Neck Cancer Symptom Index-22 adequately reflects symptom and side effect concerns of advanced HCN patients as well as oncology physicians. This instrument can be used to evaluate the most important disease-related symptoms, treatment side effects, and function/well-being in patients with advanced HCNs in clinical practice and research. © 2013 U.S. Cancer Pain Relief Committee.Published by Elsevier Inc. All rights reserved.


Matsushita N.,Moffitt Comprehensive Cancer Center | Matsushita N.,Tokyo Women's Medical University | Komine H.,Moffitt Comprehensive Cancer Center | Grolleau-Julius A.,University of Michigan | And 2 more authors.
Cancer Immunology, Immunotherapy | Year: 2010

We reported that murine tumor lysate-pulsed dendritic cells (TP-DC) could elicit tumor-specific CD4+ and CD8+ T cells in vitro and in vivo. In some limited cases, TP-DC treatments in vivo could also result in regression of established subcutaneous tumors and lung metastases. By gene array analysis, we reported a high level of expression of a novel member of the cell surface class A scavenger receptor family, MARCO, by murine TP-DC compared to unpulsed DC. MARCO is thought to play an important role in the immune response by mediating binding and phagocytosis, but also in the formation of lamellipodia-like structures and dendritic processes. We have now examined the biologic and therapeutic implications of MARCO expressed by TP-DC. In vitro exposure of TP-DC to a monoclonal anti-MARCO antibody resulted in a morphologic change of rounding with disappearance of dendritic-like processes. TP-DC remained viable after anti-MARCO antibody treatment; had little, if any, change in production of IL-10, IL-12p70 and TNF-alpha; but demonstrated enhanced migratory capacity in a microchemotaxis assay. The use of a selective inhibitor showed MARCO expression to be linked to the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo, anti-MARCO antibody treated TP-DC showed better trafficking from the skin injection site to lymph node, enhanced generation of tumor-reactive IFN-gamma producing T cells, and improved therapeutic efficacy against B16 melanoma. These results, coupled with our finding that human monocyte-derived DC also express MARCO, could have important implications to human clinical DC vaccine trials. © 2010 Springer-Verlag.


News Article | February 15, 2017
Site: www.eurekalert.org

CHICAGO (February 15, 2017): Patients with a type of advanced malignant cancer of the arms or legs have typically faced amputation of the afflicted limb as the only treatment option. However, a technique that limits the application of chemotherapy to the cancerous region can preserve limbs in a high percentage of these patients, researchers from five cancer centers in the United States and Australia report in a study published online as an "article in press" on the Journal of the American College of Surgeons website in advance of print publication. The researchers used the treatment technique, known as regional chemotherapy with isolated limb perfusion (ILI), in 77 patients with treatment-resistant, locally advanced soft tissue sarcomas (STS), and were able to salvage limbs in 77.9 percent of the cases. "Isolated limb infusion is a safe and effective technique of treatment of patients with locally advanced soft tissue sarcoma who otherwise might require amputation," said lead study author John E. Mullinax, MD, from Moffitt Cancer Center, Tampa, Fla. The study, conducted over a 22-year period from 1994-2016, is the largest one to date of limb preservation using ILI for sarcoma. "Advocates for ILI in these patients would argue that, with similar long-term survival data and meaningful overall response rates, patients would much prefer a treatment that preserves the affected extremity to one that does not," Dr. Mullinax said. ILI has historically been used primarily for melanoma of the extremities and the use of this technique in sarcoma is a more novel approach. Sarcoma is a rare type of cancer in the extremities with several different subtypes; the study patients who underwent ILI had 17 different subtypes of sarcoma. The rationale for amputation of soft tissue sarcoma of the arm or leg has been to prevent the cancer from spreading to, or metastasizing to, other parts of the body. Dr. Mullinax noted that one concern with the use of ILI in these cancers is that it does not address distant metastatic disease. "The reality is that those patients who develop metastatic disease after amputation or ILI likely may already have distant microscopic disease at the time of the procedure, but the radiographic staging studies are not sensitive enough to detect it," Dr. Mullinax said. "In this sense, the treatment of the extremity disease is not to the determinant of long-term survival." In the study population, 19 patients had 21 procedures for upper-extremity disease and 58 patients had 63 infusions for lower-extremity disease. The results varied significantly for the two groups. The overall three-month response rate to ILI was 58 percent, but it was only 37 percent for those with upper-extremity disease vs. 66 percent for lower-extremity disease. Likewise, those who had upper-extremity sarcomas had a lower median overall survival than their lower-extremity counterparts, 27.9 months vs. 56.6 months. For the entire study population, the median overall survival was 44.3 months. Entering the study, all the patients had sarcomas that could only be removed with an amputation, but afterward 30 percent had a complete response to ILI, many of these because patients were able to have a surgical procedure to remove the tumors without amputation. For those who eventually needed an amputation, the median time to do so was 4.5 months following ILI. The ILI technique involves circulating the chemotherapy agents melphalan and actinomycin D in the blood vessels of the affected area of the arm or leg, and the use of a tourniquet to block the chemotherapy drugs from circulating through the rest of the body, thus creating a closed circuit. The drugs circulate in the target area for 30 minutes, and then are flushed out before the tourniquet is removed and full circulation is restored. ILI for soft tissue sarcoma of the extremities can be repeated, whereas another procedure to administer chemotherapy to the arms or legs, hyperthermic isolated limb perfusion, requires an incision to openly cannulate the vessels and generally cannot be repeated, Dr. Mullinax explained. The ILI technique requires a team to help perform the procedure such as an interventional radiology team to place the catheter in the artery before the procedure, a perfusionist to oversee the circuit and an operating room staff familiar with chemotherapy precautions, Dr. Mullinax said. "Most patients would prefer to have more time with their leg rather than face an amputation," Dr. Mullinax said. "It's known that for patients with soft-tissue sarcoma, the life-limiting disease is not in the extremity but it's actually in the metastatic disease. An inoperable sarcoma of the thigh does not affect survival to the degree that metastatic disease in the lung does." Dr. Mullinax said one limitation of the study was that it did not randomize patients between ILI and amputation, so a head-to-head comparison of response to treatment and survival cannot be performed with this dataset. The study also did not evaluate quality of life or patient-related factors for those who had limb salvage vs. those who had amputation. Co-senior authors of the study are Ricardo J. Gonzalez, MD, FACS, and Jonathan S. Zager, MD, FACS, of the Moffitt Cancer Center; other coauthors are Hidde M. Kroon, MD, PhD, of the Melanoma Institute of Australia, University of Sydney; Neel Nath, BS, and Paul J. Mosca, MD, PhD, FACS, of Duke University, Durham, N.C.; Jeffrey M. Farma, MD, FACS, of the Fox Chase Cancer Center, Philadelphia; Rajendra Bhati, MD, FACS, of Marietta Memorial Hospital, Marietta, Ohio; Danielle Hardmann, BS, and Sean Sileno, BS, of Morsani College of Medicine, University of South Florida, Tampa; and Christina O'Donoghue, MD, Matthew Perez, MD, Syeda Mahrukh Hussnain Naqvi, MD, and Y. Ann Chen, PhD, of the Moffitt Cancer Center and Research Institute. A video summary of study highlights can be viewed at: https:/ This study was presented at the 128th annual meeting of the Southern Surgical Association, in Palm Beach, Florida, in December 2016. This work was supported by a Cancer Center Support Grant to the H. Lee Moffitt Comprehensive Cancer Center and Research Institute. NOTE: "FACS" designates that a surgeon is a Fellow of the American College of Surgeons. Citation: Isolated Limb Infusion as a Limb Salvage Strategy for Locally Advanced Extremity Sarcoma. Journal of the American College of Surgeons. About the American College of Surgeons The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for all surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 80,000 members and is the largest organization of surgeons in the world. For more information, visit http://www.


PubMed | Moffitt Comprehensive Cancer Center
Type: Journal Article | Journal: Cancer immunology, immunotherapy : CII | Year: 2010

We reported that murine tumor lysate-pulsed dendritic cells (TP-DC) could elicit tumor-specific CD4(+) and CD8(+) T cells in vitro and in vivo. In some limited cases, TP-DC treatments in vivo could also result in regression of established subcutaneous tumors and lung metastases. By gene array analysis, we reported a high level of expression of a novel member of the cell surface class A scavenger receptor family, MARCO, by murine TP-DC compared to unpulsed DC. MARCO is thought to play an important role in the immune response by mediating binding and phagocytosis, but also in the formation of lamellipodia-like structures and dendritic processes. We have now examined the biologic and therapeutic implications of MARCO expressed by TP-DC. In vitro exposure of TP-DC to a monoclonal anti-MARCO antibody resulted in a morphologic change of rounding with disappearance of dendritic-like processes. TP-DC remained viable after anti-MARCO antibody treatment; had little, if any, change in production of IL-10, IL-12p70 and TNF-alpha; but demonstrated enhanced migratory capacity in a microchemotaxis assay. The use of a selective inhibitor showed MARCO expression to be linked to the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo, anti-MARCO antibody treated TP-DC showed better trafficking from the skin injection site to lymph node, enhanced generation of tumor-reactive IFN-gamma producing T cells, and improved therapeutic efficacy against B16 melanoma. These results, coupled with our finding that human monocyte-derived DC also express MARCO, could have important implications to human clinical DC vaccine trials.

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