Viacheslav Soyfer

A low-dose adrenocorticotropin test reveals impaired adrenal function in cancer patients receiving megestrol acetate therapy.

Megestrol acetate (MA) has glucocorticoid activity and can induce significant secondary adrenal suppression. We designed this study to determine the extent of adrenal insufficiency in cancer patients receiving MA by utilising a sensitive low-dose adrenocorticotropin (ACTH) stimulation test. Adrenal function was assessed by a low-dose (0.625 microg) ACTH (1-24) stimulation test in 30 patients receiving MA for metastatic cancer. 10 of the patients who failed this test underwent a standard (250 microg) test on another day. Adrenal function was also evaluated in 15 of the patients by measuring the excretion of free cortisol in 24-h urine samples. Peak serum cortisol levels following stimulation with low-dose (0.625 microg) ACTH (1-24) were <18 microg/dl in 16 of 30 (53%) patients, of whom 9 had a basal serum cortisol level of <5 microg/dl. Five of 16 poor responders to the low-dose test showed normal stimulation with the standard (250 microg) ACTH (1-24) test. Thus, adrenal insufficiency would fail to be detected by the standard high dose test in these patients. Patients who failed the low-dose ACTH (1-24) test had lower 24-h urinary free cortisol excretion (8.7+/-10.3 microg/24 h) than normal responders (35+/-12.7 microg/24 h). Impaired adrenal function is common in cancer patients receiving MA. The low-dose ACTH (1-24) test is apparently capable of revealing adrenal insufficiency undetected by the standard high-dose ACTH test. Patients receiving MA might have inadequate adrenal function during episodes of infection or after withdrawal of MA therapy and this may require prompt corticosteroid treatment.

ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of neoadjuvant chemotherapy.

ErbB-4 is a recently described growth factor receptor. Relatively little is known about its expression in human tumours. In this study, we assessed the possible role of erbB-4 as a tissue marker for soft-tissue sarcomas (STS) and its correlation with the response to chemotherapy. The histological specimen of 29 patients with STS of a limb who had received preoperative doxorubicin (ADR)-based chemotherapy were studied for the degree of necrosis and the expression of erbB-4 (by an avidin-biotin-peroxidase technique). ErbB-4 expression in the preoperative tissue samples was compared with the expression in the postchemotherapy resected tumour. The true objective response rate to preoperative chemotherapy was 34%. Wide resection of the tumour was done in 12 patients, marginal in 14, amputation in 2 and no surgery in 1. The tumour necrosis was above 90% in 9 patients, 60-90% in 12, and less than 60% in 7 patients. An increase in erbB-4 expression was more common in cases with no response to chemotherapy, while no change or a decrease in erbB-4 was more common in responsive tumours (P=0.004). No correlation could be found between the degree of necrosis or the chemotherapeutic regimen and the change in expression of erbB-4. The median disease-free survival (DFS) was longer for patients with a decrease or no change in expression of erbB-4 than for patients with increased expression. It is believed that postchemotherapy new expression or no downregulation of the erbB-4 molecule represents tumour aggressiveness and increased capability of growth and spread.

Radiation therapy for palliation of sarcoma metastases: a unique and uniform hypofractionation experience.

Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma.

Hypofractionated adjuvant radiation therapy of soft-tissue sarcoma achieves excellent results in elderly patients.

OBJECTIVE Adjuvant radiation therapy (RT) is an essential part of combined limb-sparing treatment of soft-tissue sarcoma (STS). Elderly or medically unfit patients often have difficulty in completing 6-7 weeks of standard fractionated daily treatment. Our aim was to evaluate the efficacy of a hypofractionated adjuvant approach with RT for STS in elderly and debilitated patients. METHODS 21 elderly patients were treated with a short course of adjuvant RT (39-48 Gy, 3 Gy per fraction) for STS. The medical records of the patients were retrospectively reviewed for local or distant recurrence and side effects of RT. RESULTS At a mean 26 months of follow-up, three local recurrences (14%) were detected. Eight patients (38%) had lung metastases during the observed period. Three of them died from metastatic disease. The hypofractionated radiation was well tolerated with minimum long-term side effects. CONCLUSION Hypofractionated adjuvant radiation appears to be an effective treatment in terms of local control in elderly and debilitated patients. ADVANCES IN KNOWLEDGE The results of this study might provide an alternative to commonly used standard fractionation of radiotherapy in sarcoma patients.

AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors.

Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors.

Primary high-grade soft-tissue sarcoma of the buttock: a rare but distinct clinical entity

OBJECTIVE Sarcoma arising in the region of the buttocks is a rare entity and therefore no consensus regarding management exists in the literature. METHODS 16 patients diagnosed with localized, non-metastatic primary soft-tissue sarcoma (STS) in the buttock area, who were consecutively treated between 2005 and 2013, were retrospectively evaluated for the rate of local control, distant metastases and overall survival. RESULTS Most tumours were classified as high grade (87.5%). The average time between the appearances of symptoms to diagnosis of sarcoma was 4.5 months. At the end of the observation period, 7 (44%) patients were alive without signs of progressive disease, 37.5% patients died as the disease progressed, 13 patients were free of disease and 3 (19%) patients were alive with signs of progressive disease. Seven (44%) patients developed local recurrence. Six (37.5%) patients developed distant metastases. The lung was the most common site of distant failure (four patients); other sites were the liver as well as the adrenal gland and kidney (one patient). Four patients had both distant and local progression, three patients experienced isolated local recurrence and two patients developed isolated distant metastases. 5-year local recurrence-free survival was 58% and 5-year distant metastases-free survival was 63%. CONCLUSION It is unclear whether to subsume STS of the buttock under the rubric of pelvic tumours or tumours of the lower extremity. Either way, STS of the buttock seems to be characterized by local control, freedom from distant relapse and survival, which is inferior to accepted standards for either pelvic or lower extremity sarcomas. To improve this poor outcome, oncologists are encouraged to regard sarcoma of the buttock as a distinct clinical entity and to devise innovative therapeutic strategies accordingly. ADVANCES IN KNOWLEDGE Sarcoma of the buttock area should possibly be regarded as a distinct entity.