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W U Shipley

Publications and source records attributed to W U Shipley.

At least 19 recordsLinked to original sources
PubMed1995

The treatment of prostate cancer by conventional radiation therapy: an analysis of long-term outcome.

PURPOSE: To assess the long-term outcome of conventional external beam radiation therapy in the management of clinically confined prostate cancer and to examine the proposition that radiation accelerates tumor growth in those who fail treatment. METHODS AND MATERIALS: One thousand and forty-four men with T1-4NxM0 prostate cancer treated by conventional external beam radiation therapy at the Massachusetts General Hospital between 1977 and 1991 were analyzed. Median follow-up was 49 months. Failure was defined as: two sequential rises in serum prostate specific antigen (PSA) level; or a PSA > 1 ng/ml 2 or more years after radiation; or any clinical failure. Kaplan-Meir actuarial analyses were used to assess outcome. RESULTS: At 10 years only 40% of the T1-2 group remained disease free. When subdivided by grade, the well-differentiated tumors (Gleason 1-2) exhibited a 53% actuarial 10-year disease-free survival, moderately differentiated (Gleason 3) 42%, and poorly differentiated (Gleason 4-5) 20%. The corresponding values for the T3-4 men were 33% for Gleason 1-2, 20% for Gleason 3, and 10% for Gleason 4-5. Overall the value for T3-4 tumors was 18% at 10 years. On relapse the median PSA doubling times for the T1-2 patients were predicted by histology: 18.8 months for Gleason 1-2 patients; 11.1 months for Gleason 3; and 9.6 months for Gleason 5. Significant differences were found between the Gleason 3 and the Gleason 4-5 groups (p = 0.04) and the Gleason 1-2 and the Gleason 4-5 groups (p = 0.03). A wide range of doubling times was seen within each grade group. When compared with recently reported data on selected T1-2 patients who were managed by expectant observation there was no advantage over the first decade (and certainly no disadvantage) in terms of metastasis-free survival or disease-specific survival for the irradiated Gleason 1-3 patients. However, a gain was seen for those with Gleason 4-5 tumors. CONCLUSION: Less than half of the T1-2NxM0 and less than one-fifth of the T3-4NxM0 patients receiving conventional radiation therapy were biochemically disease free at 10 years. The PSA doubling times on relapse show a wide variation. Grade was important in determining the rate of relapse suggesting that radiation does not induce a homogeneous acceleration of prostate tumors. A metastasis-free and disease-specific survival advantage was found for the poorly differentiated tumors when compared with similar patients reported in the literature who were managed initially by observation.

Aged↗
PubMed1995

Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.

PURPOSE: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. METHODS AND MATERIALS: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. RESULTS: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p = 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy there was a lower positive rebiopsy rate for arm 1 versus arm 2 patients (28 vs. 45%) and also for those with well and moderately differentiated tumors versus poorly differentiated tumors (32 and 50%). These differences were not statistically significant. Grade 1 and 2 rectal bleeding is higher (32 vs. 12%, p = 0.002) as may be urethral stricture (19 vs. 8%, p = 0.07) in the arm 1 versus arm 2. CONCLUSIONS: An increase in prostate tumor dose by external beam of 12.5% to 75.6 CGE by a conformal proton boost compared to a conventional dose of 67.2 Gy by a photon boost significantly improved local control only in patients with poorly differentiated tumors. It has increased late radiation sequelae, and as yet, has not increased overall survival, disease-specific survival, or total recurrence-free survival in any subgroup. These results have led us to test by a subsequent Phase III trial the potential beneficial effect on local control and disease-specific survival of a 12.5% increase in total dose relative to conventional dose in patients with T1, T2a, and T2b tumors.

Aged↗
PubMed1994

Early prostate cancer: the national results of radiation treatment from the Patterns of Care and Radiation Therapy Oncology Group studies with prospects for improvement with conformal radiation and adjuvant androgen deprivation.

Long-term outcome of the Patterns of Care Study and the Radiation Therapy Oncology Group are used to demonstrate the national average results of treating early prostate cancer in the United States. A group of patients with stage T1B2 disease and pathologically negative lymph nodes showed excellent 10-year survival rates and freedom from clinical evidence of disease, while prostate specific antigen (PSA) correlations in 10-year survivors indicate that 88% were clinically free of cancer and had a PSA level of less than 4.0 mg./nl., and 65% had a PSA level of less than 1.5 ng./ml. The latter group represented clinical and biochemical cures. The improvement noted in outcome of locally advanced prostate cancer treatment by Radiation Therapy Oncology Group prospective trials combining androgen deprivation and radiation therapy is presented. These trials will be extended to the poor prognosis group with stage T1,2 disease. The advantages of conformal therapy in acute and late morbidity are illustrated with preliminary evidence of improved PSA response as a result of improved technique and higher dose associated with conformal 3-dimensional treatment.

Aged↗
PubMed1994

Radical prostatectomy and radical radiation therapy for clinical stages T1 to 2 adenocarcinoma of the prostate: new insights into outcome from repeat biopsy and prostate specific antigen followup.

Assessment of outcome following radical treatment for stages T1 to T2 prostate cancer has become more sensitive and rapid with the use of serum prostate specific antigen (PSA) in routine followup. PSA has identified substantially more failure following all radical therapies than was previously detected in series using clinical end points. Furthermore, it has also allowed a better assessment of the biological potential of histologically evident residual disease, that is a positive surgical margin after prostatectomy or positive repeat biopsy 2 years after radiation. Both situations are associated with subsequent biochemical failure in the majority of patients. The stages T1 to T2 cancer group is extremely heterogenous. In the few series with PSA followup that have evaluated long-term (greater than a decade) outcome for this group some report cure rates well below 40% for surgery and radiation. When comparing the results of any radical treatment series (surgery versus surgery and radiation versus radiation, as well as radiation versus surgery) selection may have a crucial role in predicting outcome. Surgical series tend to contain more patients with stages T1 to T2a tumors of low grade who have low initial PSA values and are known to have negative nodes. These patients, when treated with radical radiation, also have a favorable prognosis. It is hoped that the introduction of screening programs will improve outcome through earlier disease detection.

Adenocarcinoma↗
PubMed1994

Radical radiation therapy in the management of prostatic adenocarcinoma: the initial prostate specific antigen value as a predictor of treatment outcome.

We studied 161 prostate cancer patients treated by radical irradiation alone without endocrine therapy in whom pretreatment and posttreatment prostate specific antigen (PSA) values were measured, and who had a minimum followup of 2 years. Outcome was analyzed in an actuarial fashion using clinical disease-free survival and biochemical disease-free survival (freedom from an increasing PSA level or a PSA level of greater than 1.0 ng./ml. 2 years following irradiation) as end points. Of the patients 54% achieved a post-irradiation nadir value in the range 0 to 1.0 ng./ml. and 29% had a nadir value that was undetectably low (less than 0.5 ng./ml.). The likelihood of achieving these values was greater among patients with early stage than locally advanced tumors. For all T stages the likelihood of being disease-free at 4 years was substantially and significantly lower when PSA was used as an end point than when clinical evaluation alone was used: stages T1 and T2 (85 patients) 41% versus 71%, and stages T3 and T4 (76 patients) 15% versus 61%. For the whole group at 4 years clinical control was 67% but biochemical control was only 26% (p < 0.05). The likelihood of being free of biochemical evidence of persistent disease at 4 years was a function of the initial PSA value (PSA less than 4.0 in 81% of the cases, 4.1 to 10.0 in 43%, 10.1 to 20.0 in 31%, 20.1 to 50.0 in 6% and greater than 50.0 in 0%). For stages T1 and T2 cancer patients with an initial PSA level of less than 15 ng./ml. (67% of all early stage cases) this value was 65% and it was even higher (73%) when poorly differentiated tumors were excluded. When the initial PSA level for stages T1 and T2 tumors was greater than 15 ng./ml. the projected 4-year rate of freedom from biochemical failure was only 7%. For stages T3 and T4 cancer patients the corresponding figures were 39% for those with an initial PSA level of less than 15 ng./ml. and 0% for those with an initial PSA level of greater than 15 ng./ml. The prognostic power of the initial PSA level was independent of stage, grade, patient age and prior transurethral resection of the prostate in a multivariate analysis. An initial serum PSA level of more than 15 ng./ml. is, therefore, a powerful predictor of probable failure with conventional radiation therapy. Serum PSA monitoring is a sensitive detector of early relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1994

The effect of pelvic radiation therapy on serum levels of prostate specific antigen.

To determine the effect of prostatic irradiation on the production of prostate specific antigen (PSA), serum PSA levels were measured in 36 men who received pelvic irradiation (45 to 65 Gy.) for nonprostatic malignancies, and compared with those of a control group of 79 men of comparable age without prostate cancer or prior pelvic irradiation identified from the records of the Massachusetts General Hospital internal physicians. The median PSA level was lower in the irradiated group than in the control group (0.65 versus 1.1 ng./ml.). Of the irradiated patients 47% had undetectable PSA levels versus 20% of the controls (p = 0.004, Fisher's exact test). A group of 27 prostate cancer patients who received up to 68 Gy. 8 to 16 years (median 10 years) previously and who remained clinically disease-free were also studied. The median PSA level was less than 0.5 ng./ml. The proportion of patients with undetectable PSA levels was significantly higher than that of the controls (p < 0.001) but it was not significantly different from those irradiated for other pelvic cancers. Of those patients 67% had an undetectable PSA level and 78% had a level of less than 1 ng./ml. Our study suggests that radiation therapy results in a permanent decrease in PSA production by the prostate gland and that patients whose PSA values do not reach less than 1 ng./ml. following radical radiation therapy for prostate cancer are unlikely to be long-term clinical disease-free survivors.

Aged↗
PubMed1994

PSA screening.

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Adenocarcinoma↗
PubMed1993

Residual disease after radical surgery or radiation therapy for prostate cancer. Clinical significance and therapeutic implications.

Radical treatment for prostate cancer aims at complete eradication of tumor. This review of published data makes clear that the goal is less frequently achieved than commonly presumed. Following radical prostatectomy extracapsular disease, carrying a significant risk of local recurrence, is found from 12-68% of the time depending on the clinical tumor stage. Local regrowth is associated with a poorer prognosis. A substantial proportion of patients whose prostate glands are rebiopsied more than 18 months after radiation therapy also have residual tumor. This again predicts for clinical relapse. The likelihood of a positive rebiopsy is dependent on original tumor size and current prostate specific antigen (PSA) levels. Strategies for managing residual disease are critically discussed.

Age Factors↗
PubMed1993

Adjuvant irradiation after radical prostatectomy for adenocarcinoma of prostate: analysis of freedom from PSA failure.

A total of 84 consecutive men with extracapsular disease after radical prostatectomy who received postoperative irradiation and no adjuvant endocrine therapy were analyzed. Failure was defined as the development of clinical disease recurrence either locally or at a distant site, the development of detectable prostate-specific antigen (PSA) when postoperatively it had been undetectable, or any rise in PSA when postoperatively it still had been detectable. Sixteen of the 84 men had nodal disease. Overall, five-year actuarial freedom from relapse was 60 percent. For node-negative men, it was 64 percent and for node-positive men 43 percent. For the 68 men with pathologic Stage T3N0 disease, five-year freedom from relapse was 73 percent when seminal vesicles were negative and 43 percent when involved. Tumor grade also predicted the likelihood of recurrence. In a multivariate analysis the time interval from surgery to radiation and the level of postoperative PSA (detectable versus undetectable) did not influence the likelihood of relapse nor the median time to relapse. Fourteen separate patients treated with radiation alone for palpable tumor recurrence were also analyzed. Fewer than 40 percent were disease-free only two years after irradiation. We conclude that when treatment failure is defined in biochemical as well as clinical terms postoperative irradiation reduces the rate of relapse at five years relative to recently reported series in which adjuvant irradiation was not given. The additional morbidity is low. Whether or not this will translate into an overall cause-specific survival gain is currently unclear.

Adenocarcinoma↗
PubMed1992

Deoxyribonucleic acid flow cytometry in invasive bladder carcinoma: a possible predictor for successful bladder preservation following transurethral surgery and chemotherapy-radiotherapy.

Tumor deoxyribonucleic acid (DNA) ploidy was evaluated as an objective parameter that may correlate better with the responsiveness of bladder cancer to chemotherapy plus radiotherapy than do clinical features or histopathological subtypes. A total of 40 patients with localized muscle-invading bladder cancer (clinical stages T2 to T4) underwent prospective treatment on a potential bladder preserving protocol. Tumors of 37 of the 40 patients were analyzed by DNA flow cytometry of multiple paraffin embedded specimens. Transurethral resection, neoadjuvant chemotherapy and 40 Gy. radiotherapy plus cisplatin were followed by urological reevaluation of the tumor (a complete response required a negative biopsy and a negative urine cytology study). A total of 7 noncomplete response patients underwent immediate radical cystectomy whereas the full bladder sparing treatment (radiotherapy to 64.80 Gy. plus cisplatin) was given to 23 complete response patients and 7 noncomplete response patients who were unsuited for surgery. Of the tumors 22 (59%) were purely aneuploid and 10 (27%) were purely diploid. Five tumors contained aneuploid and diploid patterns in different tumor specimens (partly diploid). Current status with a 30-month median followup in surviving patients includes an 82% overall survival rate in the aneuploid group versus 47% in the diploid/partly diploid group. Of all the patients 68% are free of invasive tumor: 82% in the aneuploid group versus 47% in the diploid/partly diploid group. By multivariate analysis pure aneuploidy was significantly (p = 0.05) correlated with freedom from invasive tumor in the bladder (either as persistence or as recurrence) and approached significance (p = 0.08) in correlation with overall patient survival. A longer observation time will be required to confirm this unexpectedly good outcome for patients with pure aneuploid tumors. We hypothesize that pretreatment DNA ploidy status may become a clinically useful prognostic factor in selecting patients for successful treatment with transurethral surgery and neoadjuvant chemotherapy plus radiotherapy.

Clinical Protocols↗
PubMed1992

The role of radiotherapy in patients with advanced seminomatous germ cell tumors. Controversies in management. Part 2.

The role of radiotherapy in the management of advanced seminomatous germ cell tumors remains controversial. The authors review the available literature, and recommend radiotherapy for stage II seminoma with bulky abdominal metastases (greater than 10 cm) under the following circumstances: As primary therapy only if the patient cannot or will not be treated with chemotherapy; as an adjuvant following chemotherapy in patients with residual masses of any size. Similar recommendations are made regarding the role of radiotherapy in the management of extragonadal seminoma outside the central nervous system.

Dysgerminoma↗
PubMed1992

Radiation therapy for testicular seminoma: controversies in the management of early-stage disease.

Subdiaphragmatic irradiation remains the standard treatment for patients with stage I and IIA testicular seminoma. Elective mediastinal irradiation is not indicated. In well-selected patients with stage I disease, aggressive surveillance may be a reasonable alternative to elective irradiation. We believe that bipedal lymphangiography is useful in staging, radiation field design, and follow-up. Other controversies in the radiotherapeutic management include the optimal radiation dose and appropriate target volume.

Dysgerminoma↗
PubMed1992

Radiotherapy and chemotherapy in invasive bladder cancer with potential bladder sparing.

The standard treatment in the United States for patients with muscle infiltrating tumors is radical cystectomy with or without radiation treatment. The results of such treatment have been generally unsatisfactory, with 40% or more patients developing systemic disease with a 5-year survival rate of less than 50%. Combination chemotherapy employing both cisplatin and methotrexate can produce a 30% to 50% clinical complete response rate (negative biopsy, negative urinary cytology) of the primary tumor. Although the optimal combination of chemotherapeutic agents has not yet been determined, it is unlikely that combination chemotherapy alone, even in completely responding patients, will be adequate to rid the bladder of a primary invasive transitional cell carcinoma. Additional therapy by either surgery or external beam radiotherapy seems warranted owing to the high likelihood that there will be residual microscopic tumor in the bladder. Concomitant systemic chemotherapy and external beam radiotherapy produces complete remissions in 65% to 90% of patients. Follow-up of from 3 to 5 years following full chemoradiotherapy will be necessary to be certain that the bladder has been sterilized of cancer. Combined cisplatin and external beam radiation (using a boost technique that spares the section of the bladder uninvolved with tumor) does not seem to enhance local soft-tissue toxicity (relative to the radiotherapy alone) with the exception of the neurotoxicity seen with intra-arterial cisplatin. Debulking TURB tumor appears to improve the local success rate for patients being considered for bladder preservation with the use of the combination of systemic chemotherapy and/or radiotherapy. Not all patients respond to concomitant chemotherapy and radiation therapy. Our current approach is that the selection process must be carried on at several points during the treatment. Only patients who respond completely to the initial courses of chemotherapy and radiation should be carried to a full radiation dose. In the absence of a complete response following upfront chemotherapy and 4000 cGy in combination with additional cisplatin courses, cystectomy at that point is the recommended treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Cisplatin↗
PubMed1991

Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706.

Significant late intestinal and urinary morbidity from external beam irradiation for adenocarcinoma of the prostate has been a constant concern of both the urologist and the radiation oncologist. We analyzed two large Radiation Therapy Oncology Group trials (7506 and 7706) using primary irradiation in the treatment of local or locoregional adenocarcinoma of the prostate to assess morbidity via the Radiation Therapy Oncology Group scoring scheme (grade 1-5). One thousand twenty patients were treated in total with a minimum follow-up of 7 years in the surviving patients. There was a 3.3% incidence of intestinal complications defined as grade 3 toxicity or more with .6% of patients experiencing bowel obstruction or perforation. Urinary complications defined as grade 3 toxicity or more were found in 7.7% of patients with only 0.5% experiencing morbidity that would require a major surgical intervention such as laparotomy, cystectomy, or prolonged hospitalization. Intestinal and urinary complications were evaluated in reference to several parameters that might have an impact on their incidence (i.e., previous laparotomy, stage of disease, hypertension, positive lymph nodes, previous transurethral resection, total dose, and energy of accelerator used). Only total dose (greater than 70 Gray) was found to have a significant impact on the incidence of the urinary complications. None of these factors had a significant impact on the incidence of intestinal complications. These data from two large multi-institutional trials represent a fair estimate of the actual incidence of major intestinal and urinary complications from external beam irradiation in the management of local and locoregional adenocarcinoma of the prostate. Since the incidence of these major complications remains very low, we believe that external beam irradiation remains an excellent alternative to radical prostatectomy in the management of these patients.

Adenocarcinoma↗