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Biomedical subjects

W R Jewell

Publications and source records attributed to W R Jewell.

At least 37 records · Page 2Linked to original sources

One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study.

PURPOSE: To determine if prolonged adjuvant treatment (2 years v 1 year) with combination chemotherapy (cyclophosphamide, methotrexate, fluorouracil [5-FU], vincristine, and prednisone [CMFVP]) in poor-prognosis breast cancer patients (estrogen receptor [ER]-negative, stage II to IIIA) would result in improved disease-free and overall survival rates. PATIENTS AND METHODS: Four hundred forty-five women with ER-negative node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) over a period of 5 years (1979 to 1984). Randomized assignments were made to either 1 or 2 years of adjuvant CMFVP. Doses were daily oral cyclophosphamide 60 mg/m2, intravenous (i.v.) weekly methotrexate 15 mg/m2, i.v. weekly 5-FU 400 mg/m2, i.v. weekly vincristine .625 mg/m2 for the first 10 weeks, and prednisone weeks 1 through 6 with doses decreasing from 30 mg/m2 to 10 mg/m2. RESULTS: The median follow-up duration is 8.6 years, with a maximum of 11.3 years. Treatment arms were not significantly different as regards either survival or disease-free survival rates (P = .33 and P = .24, respectively). The five-year survival rate is 57% on the 1-year arm and 62% on the 2-year arm. Patients with three or fewer nodes and premenopausal status were associated with improved survival. Compliance on the 2-year arm was poor, with only 37% completing the full 2 years of treatment. SWOG grade 3 to 4 toxicity was experienced by 47% of patients on the 1-year arm and by 52% on the 2-year arm. There were no treatment-related deaths. CONCLUSION: We conclude that 2-year adjuvant treatment with CMFVP is not an improvement over 1-year treatment. Moreover, 2 years of CMFVP is difficult to complete. However, the results are not definitely negative. A moderate improvement attributed to prolonged chemotherapy, especially among patients with four or more positive nodes, cannot be ruled out.

Adult↗

Pelvic exenteration: a treatment for failed rectal cancer surgery.

Local-regional recurrences of the pelvis occur as an isolated event in 4 to 24 per cent of rectal cancer patients. While radiation therapy may provide temporary relief of pain due to recurrence, only a salvage pelvic exenteration offers hope of cure in these patients. We identified and reviewed 16 rectal cancer cases with local-regional recurrence who underwent salvage pelvic exenteration for cure. There were eight men and eight women. The primary cancer was treated by AP resection (3), low anterior resection (6), Hartman's resection (6), or local excision (1). Tumor at primary resection was Stage I for two patients, II for five patients, and nine patients were Stage III. Adjuvant radiation had been given to nine patients. The type of exenteration required for curative resection was anterior (3), posterior (6), total (4), or total-sacral (3). One patient died postoperatively. Survival calculations were from time of salvage exenteration until death or last follow-up. Only six deaths have occurred with a 5-year survival of 49 per cent. Mean survival for the total group was 31 months. Salvage pelvic exenteration should be given high priority in managing local-regional recurrences of the pelvis and provides worthwhile survival.

Adult↗

Breast biopsy for nonpalpable lesions: a worthwhile endeavor?

The purpose of this study was to determine our yield of carcinoma in patients with a nonpalpable mammographic abnormality and to identify which mammographic criteria will most likely yield a positive biopsy. We conducted a review of all patients with nonpalpable mammographic abnormality who underwent needle-localized breast biopsy at our institution from 1988 to 1991. Charts of 295 patients who underwent 332 needle-localized breast biopsy were reviewed for age, family history, cancer history, mammographic findings, operative time, volume of excised breast tissue, and histology. Mammographic abnormalities were categorized as suspicious (clustered) microcalcification, stellate mass, ill-defined mass, well-circumscribed mass, developing density, or asymmetric density. The overall yield of cancer positive biopsies was 48 of 332 (14.5%). The frequency of diagnosed cancers was DCIS (8), LCIS (1), Stage I (31) and Stage II (8). The frequency that each single mammographic criteria resulted in a cancer diagnosis was: suspicious calcification (12%), stellate mass (22%), ill-defined mass (14%), well-circumscribed mass (11%), developing density (9%) and asymmetric density (0%). However, patients with both a stellate mass and microcalcifications formed the highest risk subgroup, with cancer detected 66 per cent of the time (P = 0.03).

Adenofibroma↗

Breast cancer with extensive intraductal component: treatment with immediate interstitial boost irradiation.

Extensive intraductal component (EIC) has been reported to have a prominent role in local recurrence after treatment of early-stage breast cancer with lumpectomy and irradiation. Pathologic specimens from 250 breasts (245 patients) treated between June 1982 and June 1990 with lumpectomy, immediate (boost) interstitial iridium-192 to 15-20 Gy, and external-beam irradiation to the entire breast to 45-50 Gy were reviewed. EIC was present in 61 breasts. At a median follow-up period of 58 months (range, 14-110 months), there were 10 recurrences in the 250 treated breasts. Of these 10, three were in patients from the group with EIC. The 10-year actuarial recurrence rates in breasts with and without EIC were 9.1% and 5.2%, respectively. The difference between the two rates was not significant. If an immediate boost with interstitial iridium is used in therapy, the influence of EIC on local failure is insignificant.

Adult↗

Radiobiological advantages of an immediate interstitial boost dose in conservative treatment of breast cancer.

Minimum surgery with irradiation is emerging as one of the main modalities of therapy for operable early breast cancer. Between June 1982 and June 1986, 110 breasts with Tis, T1 to T3 lesions have been treated at our institution with lumpectomy and interstitial irradiation to the tumor bed with Iridium-192 perioperatively followed by external beam irradiation. There have been two local recurrences at or near the vicinity of the primary, at a median follow-up of 60 months. To analyze the parameters that might have contributed to the local control, we have examined the treatment volumes, prescribed dose to the tumor bed, dose at the core of the tumor bed, and dose to the surrounding normal tissue. Immediate interstitial implant has the radiobiological advantage of delivering continuous low dose irradiation, immediately upon removal of gross tumor to residual foci. Implantation of the afterloading catheters intraoperatively facilitates accurate dose delivery and avoidance of geographical misses. By precise treatment of any residual foci, immediately upon removal of the gross mass, perioperative interstitial irradiation improves local control and by facilitating less radical surgical excision, leads to better cosmetic results.

Brachytherapy↗

Treatment options in early breast cancer.

Conservative management of early breast cancer with limited surgical excision and radiotherapy is now being accepted as a viable alternative to mutilating surgical procedures. In this paper, the major steps in the historical development of conservative management are traced, and the results of the current randomized trials are summarized. An innovative method used at the University of Kansas Medical Center delivers a "boost" dose to the tumor bed with interstitial Ir-192 immediately following resection of the primary tumor mass. The results obtained in terms of local control and cosmesis with this technique are presented, and the current state of the art is discussed.

Adult↗

Advanced gastric leiomyosarcoma.

This is a retrospective review of twenty-two patients surgically treated for leiomyosarcoma. All but two patients had an advanced tumor of at least 8 cm size or involving contiguous structures. The most commonly performed operation was subtotal gastrectomy. The gastric resection required en bloc resection of contiguous structures in 10 patients. Fifteen patients with curative resection had a three year survival of 58 per cent. The overall group had a three year survival of 35 per cent. Advanced gastric leiomyosarcomas present a surgical challenge to complete resection, but when the procedure is accomplished the patient has a reasonable curative potential.

Adult↗

Immediate effect of irradiation on microvasculature.

The immediate effects of irradiation on microvasculature in muscle in an animal model are described in this paper. By using triple isotopes of 125I, 131I, and 22Na, the transcapillary transfer of albumin from the vascular bed to the extravascular space is determined in terms of mg/g of tissue, after single doses of 2 to 14 Gy. These results reveal an increase in the extravascular albumin immediately after irradiation and suggest an instantaneous compromise in vascular permeability even after 2 Gy. This effect was apparently dose related.

Animals↗

Cosmetic results in early breast cancer treated with lumpectomy, peri-operative interstitial irradiation, and external beam radiation.

Patients with operable breast cancer were treated at the University of Kansas Medical Center with lumpectomy, peri-operative interstitial Iridium, and external beam radiotherapy, and concomitant adjuvant chemotherapy in a majority of node positive cases. Examination of the cosmetic results in 85 breasts followed for at least 2 years, at a median of 41 months revealed 20% to be excellent, 44% to be very good, 24% good, 9% fair, and 4% to have poor results. In this paper cosmesis is analyzed with reference to the size of the primary, its location, age of the patient, whether the patient received adjuvant chemotherapy, and whether the regional nodes were treated. In this group of patients, the size and the site of the primary, patient's age, and whether adjuvant chemotherapy was administered or not, did not adversely affect the aesthetic outcome. Treatment of the regional nodes gave a worse mean cosmetic score compared to the group in whom only the breast was treated (37.51 vs. 58.98 respectively, p less than 0.001). Among the 11 patients with fair/poor cosmesis, all had regional nodal treatment, 7/11 had inner quadrant lesions, and 7/11 had lesions greater than T1. Further follow-up and accrual would be needed to confirm our results and affirm if other factors would change.

Adult↗

Intraoperative implantation radiation therapy plus lumpectomy for carcinoma of the breast.

The preponderance of evidence indicates that lumpectomy plus radiation therapy produces the same survival as modified radical mastectomy in patients with early breast cancer and further suggests that the local failure rate may be lower in the patients who undergo irradiation. In this series, patients were treated with immediate implantation of the tumor bed with iridium Ir 192. There have been two recurrences in the breast from 110 breast cancers (44% had a clinical stage greater than T1, and 41% had axillary-node involvement) in 107 patients followed up for four to 52 months (25.8 +/- 13.3 months [mean +/- SD]). These preliminary data suggest that local treatment failure can be minimized by aggressive, immediate intraoperative implantation of the tumor bed with iridium Ir 192.

Adult↗

Perioperative interstitial irradiation in the conservative management of early breast cancer.

Conservation of the breast in early breast cancer with limited resection and radiation is proving to be as effective as modified radical mastectomy in survival and in loco-regional control. Management at the University of Kansas Medical Center consists of an interstitial implant at the time of lumpectomy to facilitate perioperative irradiation with Iridium-192 to the tumor bed. An axillary node dissection is also performed at that time. Two to 3 weeks later external beam irradiation is delivered to the entire breast. One hundred and twenty-three breasts in 120 patients have been treated between June 1982 and June 1986. There were 49 pathological Stage I, 63 Stage II, 8 Stage III carcinomas, and 3 carcinomas in situ, consisting of 72 T1, 43 T2, 5 T3, and 3 TIS lesions. Patients have been followed for a median of 30 months. One patient had a "true" recurrence in the breast. Another patient developed recurrence in a different quadrant. Ninety percent of the patients had good to excellent cosmetic results, 7% were considered fair, and 3% had poor results. Seven patients developed mild arm edema, 4 were found to have moderate edema, and 1 had severe arm edema. Our preliminary results indicate that interstitial irradiation immediately after excision results in excellent local control, with very satisfactory cosmesis and no morbidity due to the simultaneous excision and irradiation.

Adult↗

Breast conservation treatment with perioperative interstitial irradiation.

Limited resection of the breast combined with radiation has proved to be as effective as more radical surgery in treating early breast cancer. At the University of Kansas Medical Center, the radiotherapy consists of an interstitial implant at the time of lumpectomy to deliver an interstitial boost dose to the tumor bed with iridium-192 immediately following the surgical procedure. An axillary node dissection is also performed at the time of lumpectomy. A dose of 2,000 cGy is delivered to the tumor bed between 40 and 60 h. Two to three weeks later, 4,500-5,000 cGy is delivered to the entire breast with external beam radiation over 5-5.5 weeks. One hundred breasts in 98 patients were so treated between June 1982 and February 1986, with 2 carcinomas in situ, 40 stage I, 51 stage II, and 7 stage III cancers, consisting of 2 TIS, 54 T1, 39 T2, and 5 T3 lesions. Locoregional control with a median follow-up of 31 months was 98%. One recurrence was in a different quadrant, and the other revealed predominantly the in situ component. Immediate implant did not compromise wound healing or cosmesis. The cosmetic result was graded as good to excellent in 88% of the breasts. Our preliminary results appear to suggest a better local control with immediate interstitial irradiation.

Adult↗

Dose-dependent radiation effect on microvasculature and repair.

It has been postulated that the damage to microvasculature may be a major factor in the manifestation of late radiation damage to organized tissue. In this study, the radiation damage to microvasculature was investigated in a rabbit model during the early phases of irradiation with the use of vascular permeability as a marker. By means of a triple isotopic technique, the vascular, extravascular, and intracellular spaces could be defined. A forelimb and hindlimb of New Zealand White rabbits were irradiated with single doses of 2-30 Gy. 125I- and 131I-labeled bioscreened albumin were used to determine the changes in vascular permeability due to irradiation. The rabbits were sacrificed at various intervals post irradiation. Vascular and extravascular spaces and the respective albumin concentrations in tissue samples from irradiated limbs were compared with control values from the unirradiated contralateral limbs in each animal. The results indicated a definite increase in the vascular permeability of albumin secondary to irradiation. The increase in vascular permeability was apparent instantaneously with irradiation, even at 2 Gy. The microvascular compromise appear to be dose related. When examined at 16-24 hours post irradiation, the excess extravasation of albumin was significant at and beyond 8 Gy. At 10-30 days post irradiation, injury was not apparent up to 15 Gy. Thus there appeared to be an instantaneous injury at the capillary level due to irradiation, which appeared to be dose related. A repair process became evident as early as 16-24 hours and appeared to be dose related as well as related to elapsed time post irradiation.

Animals↗

Effect of irradiation on microvasculature: a quantitative study.

In clinical radiation therapy, normal tissues and organs are unavoidably irradiated during the course of treatment of neoplastic diseases. Rubin and Cassaret [Clinical radiation pathology. Philadelphia: W.B. Saunders, 1968; Vols 1, 2] have postulated that microvascular damage may be the major contributing factor to late manifestation of radiation damage. It has been theorized that vascular leakage of the protein-rich fluid leads to fibrosis caused by the accumulation of fibroblasts and macrophages. Vascular changes after irradiation have been demonstrated qualitatively. To quantitate the alteration in permeability characteristics at different doses and time-dose fractionations, we have developed an isotopic technique using 125I, 22Na, and 3H2O that allows us to define vascular, interstitial, and intracellular water spaces. Using these values it is possible to quantitate the vascular changes and membrane integrity. Results show that the permeability of the vascular bed is altered by irradiation.

Animals↗

Intraarterial chemotherapy and hyperthermia for pain control in patients with recurrent rectal cancer.

For the majority of patients with unresectable recurrence of rectal cancer, persistent pain is the most distressing problem. This brief study describes a method to control pain in 10 patients with unresectable rectal cancer confined to the pelvis after standard therapy failed. All of the patients had percutaneous placement of infusion catheters in both internal iliac arteries. A continuous intraarterial infusion of 800 mg/m2 of 5-fluorouracil per day was given for 7 days and 10 mg/m2 of mitomycin C was administered as a bolus injection on the seventh day only. Four patients also received whole body hyperthermia by way of a Erbotherm 434 mHz microwave generator on the second and fifth days of infusion. Relief of pain occurred in three of the six patients who received intraarterial chemotherapy only. All four patients who also received hyperthermia achieved prolonged pain relief when it was added. We have concluded that intraarterial chemotherapy may be beneficial in patients with uncontrolled pelvic pain due to recurrent rectal cancer. The addition of hyperthermia may augment the benefit.

Aged↗

Local recurrence in adenocarcinoma of the rectosigmoid colon after curative surgical resection.

Between January 1975 and January 1982, 157 patients with a diagnosis of adenocarcinoma of the rectosigmoid colon underwent curative surgical resection. The median follow-up was three years (range, 2.5 to 9 years). Two patients were excluded from the study for staging purposes because they received preoperative radiation. The remaining patients were categorized in the following stages: carcinoma in situ-3; A-14; B(1)-14; B(2)-41; B(3)-8; C(1)-1; C(2)-70; and C(3)-4. The overall local recurrence rate was 41 percent. The local recurrence according to stage was as follows: stage A-1/14 (7 percent); B(1)-2/14 (14 percent); B(2)-15/38 (39 percent); B(3)-3/8 (38 percent); C(1)-0/1; C(2)-31/56 (55 percent); and C(3)-4/4 (100 percent). Seventeen patients in stages B(2) and C(2) received postoperative irradiation. Only two patients (2/17, or 12 percent) recurred locally. In this study the local recurrence rate for patients undergoing curative surgical resection only was very high, especially in patients with advanced stage of disease (B(2) to C(3)). There is evidence that postoperative radiotherapy could minimize the local failure rate.

Adenocarcinoma↗

Treatment of renal cell carcinoma with renal infarction, delayed nephrectomy, medroxyprogesterone, and xenogeneic immune RNA.

The authors have used xenogeneic immune ribonucleic acid (RNA) in the treatment of patients with renal cell carcinoma. This has been used in conjunction with renal artery embolization, delayed nephrectomy, and progestational therapy, using immune RNA derived from sheep cell lymphocytes immunized with patient's tumor. Four of 5 patients with Stage I disease had extremely large primary tumors. This group is alive with no evidence of disease at twelve to twenty-four months. There are no Stage II tumors in this group. One patient with Stage III tumor is alive at twenty-two months without evidence of disease. Three patients with metastases are stable at five to twenty-two months. Two patients have progressive disease at three and six months. This treatment has not been effective in patients with massive tumor burden. The results in the other groups are encouraging.

Carcinoma, Renal Cell↗