The cancer journal from Scientific American最新文献

Purpose: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described.

Patients and methods: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years.

Results: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years.

Discussion: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.

Purpose: Elective regional irradiation (ERI) of sites of likely tumor spread has been common radiation oncology practice for decades. It is based, in part, on the assumption that cancer often spreads in an orderly fashion and that an improvement in regional control will increase survival.

Method: The clinical data regarding the impact of ERI on local-regional control vs survival are reviewed for a variety of tumor sites.

Results: Improvements in survival with ERI have been reported in some clinical situations. For most, however, survival improvements have been difficult to realize. In most clinical situations, the realistic improvement in survival that is achievable with ERI is small and would be difficult to document in reasonably sized clinical trials.

Discussion: The dose-response relationship for the impact of ERI on survival is discussed. A hypothesis suggesting that a reduction in the dose of ERI may improve the therapeutic ratio of ERI (with respect to its impact on survival) is presented.

Purpose: To examine hypoglycemia associated with a non-islet-cell tumor caused by the secretion of abnormal insulinlike growth factors.

Patient and methods: We describe a 54-year-old woman with a massive solitary fibrous tumor who experienced worsening hypoglycemia with suppressed levels of insulin and insulinlike growth factor I but abnormally "normal" levels of insulinlike growth factor II.

Results: Efforts to control her symptoms with frequent meals, prednisone, and intravenous dextrose infusions were only partially successful. Attempts at reducing the tumor size by embolizing its arterial supply and percutaneous alcohol injections were unsuccessful, and the patient died 24 hours after surgical debulking.

Discussion: Patients with non-islet-cell tumor hypoglycemia usually have abnormally high levels of an incompletely processed precursor of insulinlike growth factor II, which is more bioavailable than the normal molecule. In some patients, treatment with corticosteroids and growth hormone increases blood sugar levels, but the most effective therapeutic approach is to resect or debulk the tumor.

Purpose: To evaluate the frequency of NY-ESO-1 expression in cultured lung cancer cells and to determine if this cancer-testis antigen can be presented for recognition by an HLA-restricted cytolytic T-cell clone specific for NY-ESO-1.

Methods and results: Reverse transcriptase and polymerase chain reaction amplification techniques were utilized to screen a panel of lung and esophageal cancer cell lines for expression of NY-ESO-1 encoding a recently identified cancer-testis antigen. NY-ESO-1 expression was detected in 11 of 16 small cell lung cancer lines, three of seven non-small cell lung cancer lines, and zero of 12 esophageal cancer lines. 5-Aza-2' -deoxycytidine induced expression of NY-ESO-1 in lung cancer cells. Expression of HLA-A31 by plasmid transfection or retroviral transduction enabled recognition of lung cancer cells by an HLA-A31-restricted cytotoxic T lymphocyte clone specific for NY-ESO-1.

Conclusions: NY-ESO-1 expression may be analogous to MAGE gene expression in lung cancer lines in terms of frequency and mechanism of transcriptional regulation. Furthermore, NY-ESO-1 can be presented on lung cancer cells for recognition by HLA-restricted cytotoxic T lymphocytes. Further investigation is warranted to determine if NY-ESO-1 can be exploited for the immunotherapy for lung cancer.

Purpose: The use of further radiotherapy among patients with soft tissue sarcoma that recurs in a previously irradiated area is controversial. Presented is a review of our 7-year experience with brachytherapy for recurrent soft tissue sarcoma.

Methods: A retrospective review was performed of 26 patients who underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated field. After-loading brachytherapy catheters were placed at the time of surgical extirpation of the sarcoma within a single-plane implant by use of 1-cm intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until the fifth to seventh postoperative day to allow initial wound healing. The prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and the dose was specified at 0.5 cm from the plane of the implant. The anatomic locations treated included lower extremity (N = 10), upper extremity (N = 7), trunk (N = 7), and head and neck (N = 2).

Results: Total tumor extirpation, confirmed by negative frozen section margins, was accomplished in all cases. The mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy +/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue transfer flap was placed over the bed of resection in 13 cases. Complications occurred in five patients including, three with wound breakdown, one with osteonecrosis, and with neuralgia. Operative intervention was required in four of the five patients with complications; each of the patients requiring operative intervention for wound-related complications had undergone primary wound closure without tissue transfer. Recurrence of disease occurred in 13 patients: nine local and four distant metastases. The median follow-up was 16 months (range, 2 to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease-free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%, respectively.

Conclusion: Re-irradiation of recurrent soft tissue sarcoma by brachytherapy in conjunction with resection can be performed with acceptable complication rates. Local control can be achieved for the majority of patients who would otherwise require more radical surgical procedures.