Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.     

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET)

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-¹¹C)-tyrosine by ¹¹C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-¹¹C)-Tyrosine in 0.1 N NaH₂PO₄ buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-¹¹C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-¹¹C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.     

Huntington's disease: biochemical prediction by determination of GABA synthesis of cultured fibroblasts

Summary GABA synthesis in skin fibroblasts from patients with Huntington's chorea was compared with that in a control group by means of the highly specific ³H-muscimol radioreceptor assay. A significantly increased rate of GABA synthesis was found in the group with Huntington's chorea in an early cell passage. The possible use of this method for early diagnosis of Huntington's chorea is considered.

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Zusammenfassung Die GABA-Synthese in Hautifbroblasten von Chorea Huntington-Patienten im Vergleich zu einer gesunden Kontrollgruppe wurde mittels des hochspezifischen ³H-Muscimol-Radiorezeptoren-Assays untersucht. Wir fanden eine signifikante 8fache Erhöhung der GABA-Synthese bei Chorea Huntington in einer frühen Zellpassage. Es wird erwogen, diese Methode zur Frühdiagnostik von Chorea Huntington einzusetzen.

     

Blast Crisis of Chronic Myelogenous Leukemia with Tumor Formation Characterized by T-cell Features--A Case Report

We report a case of chronic myelogenous leukemia (CML) associatedwith pronounced peripheral lymphadenopathy, with the cells havingthe Philadelphia (Phl) chromosome and T-cell features. A 23-year-oldman who was diagnosed as having CML and treated with busulfanwas admitted to our hospital because of increasing hepatosplenomegalyand pronounced lymphadenopathy. An axillary lymph node biopsydisclosed that the malignant cells formed rosettes with neuraminidase-treatedsheep red blood cells (En) (95.0%) and were positive for Leu1 (91.8%). Of the cytochemical reactions, peroxidase was negativeand periodic acid-Shiff, acid -naphthyl acetate esterase andß-glucuronidase were all positive. The karyotype ofthe bone marrow cells was 46 XY Phl positive (22q–), andthat of the lymph node cells was 51 XY Phl positive +8, +9,+18, +19, +21, 22q–. He was treated with various anti-leukemicagents and irradiation. Despite such treatments, he died ofpneumonia. This is a report of a CML patients with blast crisisand tumor formation characterized by T-cell features.     

Utilidad de la embolización vascular prequirúrgica de tumores renales con trombo tumoral en la vena renal izquierda

Introduction and objectivesPreoperative renal artery embolization (PRAE) for large renal masses may be performed prior to nephrectomy in order to simplify the procedure and reduce intraoperative bleeding. The objective of this work is to determine the role of PRAE on intraoperative bleeding and postoperative complications in left renal tumors with tumor thrombus limited to the left renal vein (level 0).Material and methodsRetrospective analysis to evaluate 46 patients who underwent left radical nephrectomy and thrombectomy for the treatment of renal cell carcinoma with level 0 tumor thrombus during the period 1990-2020. PRAE was limited to those cases in which surgical access to the main renal artery was presumed a priori difficult in the preoperative imaging study (n = 9; 19.6%). Intraoperative bleeding was estimated based on the perioperative transfusion rate, and postoperative complications were categorized according to the Clavien-Dindo classification. The Chi-squared test was used for comparisons. A multivariate analysis was performed to identify predictors of transfusion and complications.ResultsThere were no significant differences in the overall complication rate (11.1% vs. 32.4%, P = .19), major complication rate (0% vs.8.1%, P = .51), or transfusion rate (11.1% vs. 19%, P = .49) between both groups (PRAE vs. non-PRAE). In the multivariate analysis, PRAE did not behave as a predictor of complications (OR:0.11, 95%CI 0.01-2.86; P = .18) nor transfusion (OR:0.46, 95%CI 0.02-7.38;P = .58).ConclusionsIn our study on left renal cell carcinomas with level 0 tumor thrombus and difficult access to the main renal artery, PRAE was not associated with increased bleeding or postoperative complications, and it did not behave as an independent predictor of these variables. Therefore, it could be used as a preoperative maneuver to facilitate vascular management in selected cases.     

Research on the cutoff tumor size of omitting radiotherapy for BCSS after breast conserving surgery in women aged 65 years or oder with low-risk invasive breast carcinoma: Results based on the SEER database

BackgroundRadiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size.MethodsThe study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010–2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan–Meier, X-tile, Cox proportional hazards model and competing risk model.ResultsA total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors.ConclusionSmall tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.     

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

New insights into tumor-host interactions in lymphoma metastasis

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual cross-talks) of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.Abbreviations APC Antigen-presenting cells - hCRP Human C-reactive protein - ICAM Intercellular adhesion molecule - IFN Interferon - IL Interleukin - iNOS Inducible NO synthase - LFA Leukocyte function associated antigen - SER Sheep erythrocyte receptor - TA Tumor-associated rejection antigens - TNF Tumor necrosis factor - VCAM Vascular cell adhesion molecule - VLA Very late activated antigen     

Photodynamic action of concanavalin A-chlorin conjugate e6 on human fibroblasts

Laboratory of Biomembranes, Institute of Applied Molecular Biology, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR I. P. Ashmarin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 2, pp. 150–152, February, 1990.