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H M Keys

Publications and source records attributed to H M Keys.

13 recordsLinked to original sources
PubMed2000

Advanced cervical cancer.

Several large, prospectively randomized clinical trials run by multi-institutional cooperative groups have established that the best treatment for advanced cancer of the cervix is primary radiotherapy with concurrent, cisplatin-based chemotherapy. In fact, patients with earlier stage cervix cancer with poor prognostic indicators (large, bulky tumors, positive pelvic lymph nodes, or unexpected parametrial disease at the time of surgery) also show a survival benefit with this approach. Adequate radiation dosing (both external beam and intracavitary) is essential. The additional benefit of periaortic lymph node irradiation is debated, but generally accepted, for patients with locally advanced disease or pelvic lymph node involvement.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.

BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Adult↗
PubMed1998

Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas.

We examined whether the cell proliferation index by MIB-1, HER-2/neu gene amplification, Gleason grade, and pretreatment level of serum prostate specific antigen (PSA) correlated with postradiation recurrence (PRR) in patients with prostatic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue sections from 42 pretreated cases of prostatic adenocarcinoma (38 needle biopsy and 4 transurethral resection specimens) were immunostained for MIB-1 (MMI, Ventana Medical Systems, Tucson, Ariz). HER-2/neu gene amplification was analyzed by fluorescence in situ hybridization using the Oncor unique sequence probe (Oncor, Gaithersburg, Md). The cell proliferation index by MIB-1 was determined by labeling index; levels of HER-2/neu were analyzed semiquantitatively. Twenty-three of 42 patients (55%) were considered to have PRR on the basis of consecutive elevations of serum levels of PSA to greater than 1.5 ng/mL after completion of treatment (mean follow-up time, 33.4 months). The cell proliferation index correlated with PRR on both univariate and multivariate analyses. Of the 23 tumors that showed PRR, 18 (78%) revealed a high cell proliferation index, compared with 6 of 19 cases (32%) that showed no PRR. Twelve of 23 cases of prostatic adenocarcinoma (52%) in the recurrent group showed HER-2/neu gene amplification, compared with 5 of 19 (26%) in the nonrecurrent group; these findings reached near significance on univariate analysis. Pretreatment levels of serum PSA also reached significance on multivariate analysis. In this preliminary study, the cell proliferation index by MIB-1 reached independent significance in predicting PRR in patients with prostatic adenocarcinoma, whereas HER-2/neu amplification by fluorescence in situ hybridization reached near significance.

Adenocarcinoma↗
PubMed1993

Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.

PURPOSE: Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS: Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS: There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION: In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.

Adult↗
PubMed1991

Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group.

Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.

Adult↗
PubMed1984

Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients.

Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible on postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized.

Adult↗
PubMed1982

Porcine sensitized lymph node cells (immunotherapy) and attenuated irradiation for infiltrative transitional cells carcinoma of bladder.

Thirty-four patients wih infiltrative bladder carcinoma, Stage B2C or higher were treated with immunotherapy and irradiation. Seventeen patients are alive, and 17 have succumbed to their disease. Eight patients underwent cystectomy after immunotherapy and irradiation; 6 of 8 are alive and well at the present time. The technique of immunotherapy is outlined. New methodology for sequential CT scans and scheduled bladder biopsies is mentioned. The 17 patients have survived twelve to sixty-nine months after immunotherapy and irradiation. Downstaging is demonstrated based on sequential CT scans of the bony pelvis and histologic biopsy. The biopsies reveal eosinophilia and multinucleated giant cells, a specific response to immunotherapy. A prospective randomized study will be initiated.

Adult↗
PubMed1981

Updating computed tomography of bladder carcinoma in assessing response to immunotherapy and attenuated irradiation.

Computed tomography (CT) was utilized as part of the surgical-pathologic-radiologic evaluation of 21 patients who were treated for bladder carcinoma with attenuated irradiation and immunotherapy. Fifteen patients had moderately infiltrative (Stage B2-C or less) disease, and it was found that a routine high resolution CT technique using a modern fast scanner delineated the tumor in most cases. More accurate assessment of tumor response to therapy and evaluation of tumor progression were facilitated using a gas insufflation technique combined with intravenous contrast fusion. This was followed in selected cases by quantitative measurements of CT attenuation values using a recently introduced CT software program. Using this program, individual pixel values were obtained in selected areas and evaluation of the resulting numerical data and pixel histograms aided in the differentiation of tumor tissue from adjacent bladder wall and mapped out areas of tumor necrosis. Our preliminary observations suggest that quantitative CT studies incorporating assessment of printouts of attenuation values of adjacent pixels within a region of interest will improve the delineation of smaller (B1/B2) lesions and will aid objective characterization of tumor tissue during and following therapy.

Adult↗
PubMed1975

Prospects for para-aortic irradiation in treatment of cancer of the cervix.

The incidence of para-aortic node metastasis in cancer of the cervix ranges from 5%to 50% in clinical Stages i-iv. Extended field irradiation is being administered more frequently because of high incidence of extrapelvic disease. The cancer of the cervix material at Walter Reed General Hospital has been analyzed as to site and time of failure to determine who might have benefited from extended field irradiation. Of patients who fail, the majority will have uncontrolled pelvic disease regardless of other involvement. Diagnostic procedures including staging laparotomy are unable to predict pelvic failure or the presence of occult distant disease in lung and bone. The maximum number of patients who could benefit from pari-aortic irradiation is lessthan 3% of a total series. It is concluded that the salvage of patients with para-aortic metastasis will be small, but for those few long-term survivors, the benefit will be great.

Adult↗
PubMed1975

Carcinoma of the cervix: a time dose analysis of control and complications.

The use of 3 dose assessment systems is compared. The Manchester approach which measures a dose to Point A and Point B; the Paris approach using rads and mgh; and Ellis's NSD approach appear to have equal value in predicting probability of pelvic control and the likelihood of complication over the dose range employed at this hospital. Control increases with higher dose schemes, but complications appear to be influenced by other variables not accounted for in the 3 systems.

Female↗