Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up

Soft tissue sarcomas (STSs) comprise ∼80 entities defined by the World Health Organization (WHO) classification based on a combination of distinctive morphological, immunohistochemical and molecular features.1 These ESMO–EURACAN–GENTURIS (European Society for Medical Oncology; European Reference Network for Rare Adult Solid Cancers; European Reference Network for Genetic Tumour Risk Syndromes) Clinical Practice Guidelines (CPGs) will cover STSs, with the exception of gastrointestinal stromal tumours (GISTs) that are covered in the ESMO–EURACAN–GENTURIS GIST CPGs.2 EURACAN and GENTURIS are the European Reference Networks connecting European institutions, appointed by their governments, to cover rare adult solid cancers and genetic cancer risk syndromes, respectively. Extraskeletal Ewing sarcoma, round cell sarcoma with EWSR1-non-ETS fusion and sarcomas with CIC rearrangements and BCOR genetic alterations are covered by the ESMO–EURACAN–GENTURIS–ERN PaedCan (European Reference Network for Paediatric Oncology) bone sarcomas CPG.3 Kaposi's sarcoma, embryonal and alveolar rhabdomyosarcoma are not discussed in this manuscript, while pleomorphic rhabdomyosarcoma is viewed as a high-grade, adult-type STS. Finally, extraskeletal osteosarcoma is also a considered a high-grade STS, whose clinical resemblance with osteosarcoma of bone is doubtful. The methodology followed during the consensus meeting is specified at the end of the manuscript in a dedicated paragraph

TENIPOSIDE FOR MENINGEAL CARCINOMATOSIS OF SMALL-CELL LUNG-CANCER

A female patient with small cell lung cancer and extensive bone marrow metastases achieved a complete response after combination chemotherapy including etoposide. During maintenance therapy meningeal carcinomatosis was diagnosed. After intravenous administration of teniposide she improved dramatically during 3 months

HIGH-DOSE CHEMOTHERAPY WITH STEM-CELL REINFUSION AND GROWTH-FACTOR SUPPORT FOR SOLID TUMORS

With the help of stem cell reinfusion and hematopoietic growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs, A number of reasons may have made high-dose chemotherapy less dangerous and the fore more acceptable in a more upfront treatment setting, One of these is the addition of peripheral stem cell harvest obtained after mobilization,vith a hematopoietic growth factor alone or after chemotherapy followed by a hematopoietic growth factor, which seems to result in a faster recovery of neutrophils and platelets compared to bone marrow reinfusion alone, The combination of various hematopoietic growth factors could potentially improve hematopoietic recovery of the high-dose chemotherapy regimen, The relevance of tumor cells sometimes present in the reinfused hematopoietic stem cells is as yet unknown. High-dose chemotherapy may be interesting for a number of solid tumors such as nonseminomatous testicular carcinoma, breast carcinoma in the metastatic and adjuvant setting, ovarian carcinoma, tumors of young adults such as Ewing sarcoma and small cell lung carcinoma, In patients with refractory nonseminomatous testicular cancer there have been a number of studies performed with high-dose chemotherapy showing a 15% complete and prolonged remission, For other tumor types and settings it will be necessary to perform randomized studies before firm conclusions can be drawn, For example, this is especially important for patients with breast carcinoma with more than three positive axillary lymph nodes, Preliminary data from various groups compared to historical controls treated with standard adjuvant chemotherapy show favorable results of adjuvant chemotherapy containing high-dose chemotherapy, Many relatively small nonrandomized studies are performed in various stages of disease for ovarian carcinoma, Although there are long-term survivors reported it is currently difficult to draw firm conclusions, The potentially safer therapy of high-dose chemotherapy may reveal in the near future the role of high-dose chemotherapy in solid tumors

Sequential Backbone Assignment of Uniformly C-13-Labeled Rnas by a 2-Dimensional P(Cc)H-Tocsy Triple-Resonance Nmr Experiment

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The value of high-dose methotrexate-based neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone

Purpose: The value of high-dose methotrexate (HD-MTX)-based neoadjuvant chemotherapy was evaluated in patients with malignant fibrous histiocytoma (MFH) of bone. Patients and Methods: Since 1977, MFH of bone was diagnosed in 17 patients (12 males and five females). Ten patients (59%), completed treatment with four courses of neoadjuvant chemotherapy as follows: HD-MTX, vincristine, doxorubicin, cyclophosphamide, bleomycin, and dactinomycin, or HD-MTX, 4(1)-epidoxorubicin, and carboplatin followed by local tumor resection (n = 3), curettage-cryosurgery (n = 2), amputation (n = 2), or tumor resection-endoprosthetic replacement or allograft (n = 3). After recovery from surgery, an additional six courses of polychemotherapy, including HD-MTX in nine patients, were administered. One patient changed to cisplatin- instead of HD-MTX-containing chemotherapy postoperatively. One additional patient received only adjuvant HD-MTX-containing polychemotherapy. Neoadjuvant MTX-containing chemotherapy was contraindicated in five patients (29%) due to age, cardiac insufficiency, or mental disorder. In one patient, neoadjuvant chemotherapy was cancelled after one course due to renal failure. Treatment consisted of amputation (n = 2), one course of chemotherapy and amputation (n = 1), hyperthermic isolated limb perfusion (HILP; n = 1), intraarterial chemotherapy, radiotherapy, and endoprosthetic replacement (n = 1), and a combination of chemotherapy and radiation treatment (n = 1). Results: Five of six patients who received no HD-MTX-based neoadjuvant chemotherapy developed metastatic disease (83%); the median time to metastatic disease was 17 months (range, 3 to 44). In contrast, in 10 patients who completed treatment with HD-MTX-based neoadjuvant chemotherapy, with a mean follow-vp time of 9.8 years (range, 2.3 to 15.7) and a median follow-up time of 10.8 years (range, 2.3 to 15.7) after diagnosis, no local recurrence or distant metastases were diagnosed (P <.005). Conclusion: Neoadjuvant HD-MTX-containing chemotherapy in addition to surgery has dramatically improved the prognosis of patients with MFH of bone. (C) 1996 by American Society of Clinical Oncology

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: A feasibility study

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 mu g kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 mu g kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (greater than or equal to grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (