A new thermal dose model based on Vogel-Tammann-Fulcher behaviour in thermal damage processes.

Thermal dose models are metrics that quantify the thermal effect on tissues based on the temperature and the time of exposure. These models are used to predict and control the outcome of hyperthermia (up to 45°C) treatments, and of thermal coagulation treatments at higher temperatures (>45°C). The validity and accuracy of the commonly used models (CEM43) are questionable when heating above the hyperthermia temperature range occurs, leading to an over-estimation of the accumulation of thermal damage. A new CEM43 dose model based on an Arrhenius-type, Vogel-Tammann-Fulcher, equation using published data, is introduced in this work. The new dose values for the same damage threshold that was produced at different in-vivo skin experiments were in the same order of magnitude, while the current dose values varied by two orders of magnitude. In addition, the dose values obtained using the new model for the same damage threshold in 6 lesions in ex-vivo liver experiments were more consistent than the current model dose values. The contribution of this work is to provide new modeling approaches to inform more robust thermal dosimetry for improved thermal therapy modeling, monitoring, and control.

Severe gastrointestinal hemorrhage during targeted therapy for advanced breast carcinoma.

The introduction of targeted agents has improved survival for patients with a number of types of cancer, including several breast cancer subtypes. However, these agents are not without toxicities, and the fact that many patients are now on targeted therapy for extended periods of time has presented new challenges for the management of adverse effects. Everolimus is an inhibitor of mtor (the mammalian target of rapamycin) that is used as targeted therapy for advanced, hormone receptor-positive, her2-negative breast cancer in postmenopausal women in combination with exemestane, after treatment failure with letrozole or anastrozole. Minor hemorrhagic events are relatively common with targeted agents, but life-threatening hemorrhages, although uncommon, can also occur. We report a case of life-threatening gastrointestinal bleeding in a 48-year-old woman being treated with everolimus for advanced infiltrating ductal carcinoma of the breast. The bleeding was successfully treated with 13 sessions of endoscopic hemostasis using argon plasma coagulation.

Immune toxicities and long remission duration after ipilimumab therapy for metastatic melanoma: two illustrative cases.

New antitumour immunotherapy strategies for stage iv metastatic melanoma include ipilimumab, a monoclonal antibody against ctla-4. Patterns of response with cancer immunotherapy differ from those with cytotoxic chemotherapy. We present two cases of long-duration immune-related responses with ipilimumab in a phase ii trial. A 66-year-old woman with multiple lung metastases from a scalp primary melanoma received 4 doses of ipilimumab with mixed clinical response. However, after the first maintenance dose, she developed severe ileitis and colitis that responded to steroid therapy. Four months later, she had surgery and radiotherapy for a single brain metastasis. Radiologically, stable disease continued for 36 months after the last ipilimumab dose, and partial response for 5 years after ipilimumab start. A 54-year-old man with cervical lymph node and pulmonary metastases from a scalp primary melanoma received three induction doses of ipilimumab. He developed alopecia universalis and widespread vitiligo, and he discontinued treatment because of hypophysitis. Maintenance ipilimumab was started after a 6-month drug-free interval, with no further adverse events over 15 cycles. At week 12, computed tomography imaging showed no lung metastases and partial response in a supraclavicular lymph node, which was positive on positron-emission tomography. Five years after starting ipilimumab, the supraclavicular lymph node was calcified, and the patient was off steroid therapy and asymptomatic. The foregoing patients demonstrate long responses with ipilimumab (in association with delayed severe colitis in one case, and a constellation of immune events, including alopecia universalis in another). Re-treatment with ipilimumab may be possible even after significant immune adverse events.

Intensive induction chemotherapy without methotrexate in adult patients with localized osteosarcoma: results of the Institut Gustave-Roussy phase II trial.

PURPOSE: To improve outcomes in localized osteosarcoma and to reduce the duration of preoperative chemotherapy, we conducted a phase ii trial assessing the efficacy of an intensive protracted regimen without methotrexate (api-ai regimen) in adolescent and adult patients with newly diagnosed disease. PATIENTS AND METHODS: Induction chemotherapy consisted of 2 cycles (4 courses) of doxorubicin 60 mg/m(2) (days 1 and 15), cisplatin 100 mg/m(2) (day 1), and ifosfamide 5 g/m(2) (days 2 and 15). The primary endpoint was good histologic response [ghr (≤5% identifiable tumour cells)]. RESULTS: From March 1993 to March 2000, 32 patients [median age: 21 years (range: 15-49 years)] were administered 126 induction courses. The median time between chemotherapy courses was 15 days (range: 12-32 days). All but 3 patients underwent conservative surgery. Toxicity was mainly hematologic, with febrile neutropenia occurring in 35% of patients and grades 3-4 thrombocytopenia in 35%. The ghr rate was 47%. The median follow-up was 64 months (range: 30-115 months). The 5-year event-free and overall survivals were 65% [95% confidence interval (ci): 48%-79%] and 69% (95% ci: 50%-83%) respectively. Two secondary hematologic malignancies occurred: 1 acute myelocytic leukemia (M5) in a poor responder with concomitant relapse, and 1 myelodysplastic syndrome in a patient achieving ghr. CONCLUSIONS: Despite hematologic toxicity, the results observed with the api-ai regimen compare favourably with those observed during previous induction chemotherapy containing methotrexate in adult patients and the pediatric population treated at our institution. These promising results have to be validated by an ongoing national multicentre trial coordinated by the French Sarcoma Group.

Retrospective practice review of treatment of metastatic non-small-cell lung cancer with second-line erlotinib.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIS) and chemotherapy have both demonstrated efficacy in recurrent metastatic non-small-cell lung cancer (NSCLC) following failure of first-line platinum-based chemotherapy. Although the 3 available therapeutic agents-docetaxel, erlotinib, and pemetrexed-have significantly changed the treatment landscape for recurrent NSCLC, the optimal selection of second- and third-line therapy has not been established. This practice review examines the outcomes in clinical practice of using second-line erlotinib followed by third-line chemotherapy in the treatment of recurrent metastatic NSCLC. METHODS: We conducted a retrospective review of nsclc patient charts at three Canadian institutions. Patients with recurrent nsclc who had received second-line erlotinib therapy followed by third-line chemotherapy were selected by census. A chart review assessed key outcomes that included time to progression (TTP), response, and change in performance status. Outcomes for specific patient subgroups were also examined. RESULTS: We identified 35 patients for this retrospective practice review. First-line platinum-doublet therapy demonstrated a mean TTP of 6.6 months and a 46% overall response rate (15 partial responses and 1 complete response). Second-line treatment with erlotinib produced the highest mean TTP of all lines of therapy (9.2 months) and an overall response rate of 40% (all being partial responses). In the third-line setting, in which most patients received docetaxel, the mean ttp was 4.3 months and the overall response rate was 18% (all being partial responses). Subgroup analysis showed that all patient subgroups demonstrated benefit from second-line erlotinib treatment; improved benefit was observed in patients who developed rash, in female patients, in never smokers, in Asian patients, in patients with positive EGFR status, and in patients with adenocarcinoma histology. CONCLUSIONS: For patients with advanced nsclc who progressed following first-line platinum-based chemotherapy, the data demonstrate that second-line EGFR-TKI treatment is efficacious and well-tolerated and that it does not appear to diminish the benefit of third-line chemotherapy.

Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

BACKGROUND: Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. METHODS: Primary tumors were obtained from 142 patients with axillary node-positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. RESULTS: After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). INTERPRETATION: Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the 'seed and soil' theory.

[Expression of chemokine receptors by cancer cells]. / Expression des récepteurs aux chimiokines par les cellules tumorales: données et implications dans le cancer du sein.

Chemokine receptors are involved in the trafficking of leucocytes. It has been shown recently that chemokine receptors (CXCR4, CCR7...) are expressed by breast cancer cells and could be involved in the metastasis phenomenon. Since this discovery, new data have been generated in this topic. These data confirm that chemokine receptors are involved in the occurrence of metastases, suggest that their expression is regulated by genes involved in the carcinogenesis and/or angiogenesis (VHL...) and that inhibitors could be of interest in the treatment of breast cancer. In this paper, we will review all these data and will discuss the perspectives that opens this new concept.

Cytopathology in cancer of larynx.

The results of brush cytological smears were compared with the microscopical examination of punch biopsies obtained from 60 patients with suspected cancer of the larynx. The bronchofibroscope 'Olympus BF B3' was used to obtain the brush specimens. The results of cytology and pathology specimens were found identical in 93.3% of cases. Comparison between our results and previous similar work is presented.