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Elevated levels of epidermal growth factor receptor in head and neck cancer have been extensively reported and are correlated with poor prognosis. The combination of cisptatin and 5-fluorouracil is a standard treatment regimen for head and neck cancer, with radiation representing another therapeutic option. Six head and neck cancer cell lines were used to study the cytotoxic effects of combining ZD1839 ('lressa'), a new selective epidermal growth factor receptor tyrosine kinase inhibitor, and radiation. Two of the cell lines were also used to study the combination of ZD1839 and cisptatin/5-fluorouracil. Cytotoxic effects were assessed by the MTT test. The results indicated that ZDI839 applied before radiation gave the best effects (P=0.002); an effect that was strongest in those p53-mutated cell lines that express the highest epidermal growth factor receptor levels. The effects of ZD1839 with cisplatin and/or 5-fluorouracil were sequence dependent (P < 0.003), with the best results achieved when ZDI839 was applied first. For the triple combinations ZDI839 applied before cisptatin and 5fluorouracil resulted in a slight synergistic effect (P=0.03), although the effect was greater when ZD1839 was applied both before and during cytotoxic drug exposure. In conclusion. ZD1839 applied before radiation and before and/or during cisplatin/ 5-fluorouracil may improve the efficacy of treatment for head and neck cancer. [ABSTRACT FROM AUTHOR]

Purpose: The recent Z0011 trial demonstrated equivalent survival in patients (pts) with breast cancer (BC) and 1 to 2 positive SLNs who were randomly assigned to SLN biopsy (SLNB) alone or followed by axillary lymph node dissection (ALND). More importantly, regional recurrence with SLNB alone was less than 1%, despite the fact that an estimated 27% of patients had additional metastases in the undissected axillary nodes. Currently, many teams do not recommend anymore ALND when the pts receive systemic therapy and whole breast irradiation (WBI). However, the optimal design of radiation fields for patients with positive SLNs who do not undergo ALND is uncertain. This prospective study was designed to define the dose distribution and coverage of level I and II of the axilla using only tangent fields after conservative surgery (CS) or total mastectomy (TM). Methods and Materials: Thirty four pts were included in this analysis. 5 (14.7%) had TM and 29 (85.3%) had CS. Median age was 54 (30-90) years. All pts had 3D conformal RT. The level I/II/III axillary volumes were contoured using the RTOG contouring atlas. The total dose delivered was 50Gy in 25 fractions (n = 11) or the same dose (D) followed by a boost of 10 to 16Gy (n = 23). Pts were analyzed according to the total dose delivered in these 2 groups: group 1 (50Gy; n=11), group 2 (60 to 66Gy; n=23). A subgroup analysis was also performed in the group 2 regarding the initial tumor site and delivered dose: 66Gy to the upper quadrant (n = 14 group 2a) vs the lower quadrant (n = 4; group 2b) vs 60Gy to the upper quadrant (n = 5, group 2c). All dose-volume-histograms were analyzed. Mean, median values derived from level I and level II volumes were compared using t-test. Level of significance was set at p-value = 0.05. Results: In the whole population, the median D delivered to level I and II was 16.2 and 1.7 Gy, respectively. The mean D at these levels were 21.2 Gy (rang: 1.0-48.1) and 5.0 Gy (0.1-40.9), respectively. The volume of 95% and 50%-isodose coverage were 0 cm³ and 17.2 cm³ for level I and 0 cm³ for level II. The mean values for level I and II volumes were 1.4 cm3 and 21.9 cm³, respectively. According to the total D delivered (with or without boost), no difference was found between group 1 and group 2 in terms mean, median, and minimal D delivered to axilla levels (p = 0.5 and 0.9). Conversely, the difference was statistically significant for maximal D (p = 0.01). Furthermore, there was no difference according to tumor site and total dose between group 2a and 2b and group 2c (p = 0.07 and 0.7). In addition, no difference was observed between irradiation of whole breast or chest wall at 50Gy (p = 0.3 and 0.7). Conclusion: In patients undergoing conservative surgery or post-mastectomy radiotherapy, tangent fields provide a limited coverage of level I and II of the axilla as defined by the RTOG contouring atlas. In addition, these regions were mainly underdosed with au total dose < 30Gy even for pts who received 66Gy at the upper quadrant. These data should be considered when only tangent fields are planed to target the axilla in patients with metastases in SLNB positive without axillary dissection. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT)., Patients and Methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry., Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95%CI [0.221-0.599]., Conclusion: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and compared with molecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.

Background: Solitary extramedullary plasmacytoma (SEP) represents a rare separate clinical pathological entity; it is radiosensitive, curable, and unrelated to myeloma. Only 15 cases have been reported., Patients and Methods: Authors report two well documented cases of dural plasmocytomas mimicking meningiomas. This paper points out differences between plasmacytomas, with very different initial presentation, and other meningeal tumors including extensive radiological investigations. Diagnostic options and outcomes are discussed., Conclusion: With solitary plasmacytomas, radiological diagnosis is difficult to assess. Serum is generally free of monoclonal protein. The importance of the most recent techniques in ruling out other pathological entities is stressed. Histopathological examination is required to document a monoclonal type of plasma cell tumor. Treatment includes surgery and radiotherapy. Differential radiological diagnosis will be discussed.

The subunit composition of phosphofructokinase from normal and malignant blood cells has been investigated by means of immunologic, electrophoretic, and chromatographic methods. Immunoprecipitation tests were performed with three specific antisera recognizing each of the basic subunits of human phosphofructokinase: muscle, M-type; liver, L-type; and fibroblast, F-type. Mature polymorphonuclear cells contain mainly L-subunits, while lymphocytes and platelets contain hybrids formed of L and F subunits; these hybrids can be electrophoretically separated. Red cell phosphofructokinase is composed of L and M subunits, as judged by its reactivity with anti-L and anti-M-type antisera. The various M-L hybrids composing red cell phosphofructokinase could be only separated by chromatography on DEAE-Cellulose. Lymphocytes from patients with chronic lymphocytic leukemia and lymphoblasts from patients with acute lymphoblastic leukemia contain phosphofructokinase forms similar to those from normal lymphocytes, while the immature granulocytic cells (leukemic myeloblasts and myeloid cells of chronic myeloid leukemia) are characterized by a reinforcement of enzyme inhibition by anti-F-type antiserum. Lymphoid lines in culture (Epstein-Barr virus (EBV)-induced or malignant lymphoma-derived lines) are characterized by the indistinctive expression of all three basic subunits, similar to that found in some fetal tissues. This article represents the first description of the isozymic nature of phosphofructokinase in platelets and white blood cells and of its changes with malignancy and cell culture. This enzyme might represent a useful marker in the characterization of the leukemic cells.

Isozymic heterogeneity of human phosphofructokinase was investigated by means of ATP inhibition, immunoneutralization by antihuman muscle-type and antiliver-type phosphofructokinase antisera, solubility in (NH4)2SO4 solutions, and starch gel and polyacrylamide slab gel electrophoresis. The enzymes studied by these methods were purified from various normal and malignant human adult tissues by chromatography on blue Dextran Sepharose 4 B columns. From the results of these studied we suggest that three basic phosphofructokinase isozymes could exist: muscle-type, fibroblast-type, and liver-type isozymes. Muscle-type isozyme is the single form found in adult muscle, and is involved in the enzymes from heart, brain, red cell, and testis. Fibroblast-type isozyme is found mainly in the placenta, fibroblasts kidney, and some malignant tissues. Liver-type phosphofructokinase seems to be very definitely the predominant form in mature polymorphonuclear cells, platelets, and liver. Testis and red cell phosphofructokinase enzymes definitely include msucle-type aand liver-type subunits, associated in various hybrid forms.