Prostate cancer--the therapeutic challenge of locally advanced disease.
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Adenocarcinoma↗
Biomedical subjects
J C Blasko
Publications and source records attributed to J C Blasko.
Posttreatment biopsy results following interstitial brachytherapy in early-stage prostate cancer.
PURPOSE: To assess pathologic control rates for prostatic carcinoma as determined by postimplant prostate biopsy in a large series of consecutive patients who have received permanent interstitial brachytherapy using a contemporary transrectal ultrasound-directed, transperineal, computer generated, volume technique. METHODS AND MATERIALS: Four hundred and two patients received permanent 125I or 103Pd interstitial brachytherapy as primary treatment for early stage prostatic carcinoma at the Northwest Tumor Institute between January 1988 and January 1994. Of these, 201 have consented to biopsy 12 or more months postimplant with a median follow-up of 40 months (range: 12-83 months). None had received hormonal manipulation. A total of 361 biopsies was performed on 201 patients with a range of one to six annual biopsies per patient (91 received multiple, serial biopsies). Of the 161 patients more than 12 months postimplant who have not been biopsied, most have been unwilling or unable to submit to biopsy. Only six patients with biochemical progression have not been biopsied. There was no difference in the presenting characteristics or implant parameters between those patients biopsied and those that were not. One hundred and forty-three received 125I (71%) prescribed to a MPD of 160 Gy with a median activity of 35.5 mCi, and 58 (29%) received 103Pd prescribed to a MPD of 115 Gy with a median activity of 123 mCi. Multiple biopsies were performed under transrectal ultrasound guidance, and all specimens were classified as either negative, indeterminate, or positive. RESULTS: At the time of last biopsy, 161 (80%) have achieved negative pathology, 34 (17%) remain indeterminate, and 6 (3%) have been positive. Only 2 of the 186 patients with a PSA < 4.0 ng/ml at the time of biopsy were positive. Among those 33 indeterminate patients with a subsequent biopsy, 28 have converted to negative, 2 to positive, and 3 remain unchanged to date. CONCLUSIONS: These data demonstrate at least an 80% pathologically confirmed local control rate following permanent interstitial brachytherapy for early stage prostate cancer. A higher local control rate is expected with further follow-up as the majority of indeterminate biopsies convert to negative over time. The indeterminate category of postirradiation biopsy described here includes specimens that have probably been interpreted as positive in other series, but correlate clinically and biochemically with negative biopsies. These results support the use of modern interstitial brachytherapy techniques for selected patients with early stage adenocarcinoma of the prostate.
Biopsy↗
Interstitial implantation techniques in prostate cancer.
Brachytherapy is a radiotherapeutic technique that allows the physician to implant radioactive isotopes into a body cavity or directly into tissue. Different radioisotopes have unique characteristics that the brachytherapist may utilize for a particular situation. The use of brachytherapy is part of standard radiation oncology practice in gynecological and head and neck cancer management. The prostate is approachable for interstitial implantation due to its close proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy were utilized in the treatment of prostate cancer. However, poor results due to inconsistency in achieving adequate coverage of the entire prostate and poor patient selection caused this treatment modality to fall out of favor. Technological advances over the last decade have restored attention to brachytherapy for prostate cancer. Particularly important has been the development of transrectal ultrasound, new radioisotopes such as palladium-103, computer tomography, computerized dosimetry systems, and earlier diagnosis. Modern interstitial implantation utilizing transperineal template and transrectal ultrasound guidance has resulted in improved consistency in radiation dose delivery to the entire prostate. Early results are encouraging in terms of the relatively low morbidity of the procedure, improved local control rates, and biochemical progression free survival. This has resulted in an outpatient treatment that has high patient acceptance.
Aged↗
Should brachytherapy be considered a therapeutic option in localized prostate cancer?
Contemporary prostate brachytherapy incorporates advances in computer analysis, imaging technology, and delivery apparatus, allowing exacting and reproducible results compared with historical approaches. The advances permit brachytherapy to be performed on a cost-effective, outpatient basis with low morbidity in the appropriately selected patient. Although unsettled questions remain regarding dosimetric issues, long-term outcomes, and morbidity, the weight of evidence to date appears to support the use of brachytherapy in selected patients. Brachytherapy may be considered a therapeutic option: as monotherapy for early-stage disease and also a boost following moderate doses of external beam irradiation for locally advanced disease.
Brachytherapy↗
Does brachytherapy have a role in the treatment of prostate cancer?
The goal of radiation therapy is to deliver a high dose to the tumor while preserving normal surrounding tissue. For early-stage prostate cancer, the ultimate conformal irradiation is to place radioactive sources directly into the gland either as permanent or temporary seeds. Permanent seed implantation is capable of delivering two times the radiobiologically equivalent dose of external beam irradiation to the prostate and tumor. In the past, the results of prostate brachytherapy were likely poor owing to the technical difficulty in accurately placing the radioactive seeds uniformly throughout the prostate. The use of low-dose-rate I-125 to treat high-grade cancers probably also contributed to the poorer results as compared with external beam irradiation. Over the last 10 years, however, technologic advances in transrectal ultrasonography, computer dosimetry, and template-based transperineal techniques have dramatically improved the accuracy and consistency of the brachytherapist to place radioactive sources directly into the prostate gland. Transperineal ultrasound or CT directed seed implantation has replaced the older retropubic method. Brachytherapists are now able to accurately map out the gland prior to the implant and carefully evaluate preoperatively seed placement. The availability of such radioactive sources as iodine-125, palladium-103, and iridium-192 has also given the brachytherapist isotopes that can be more carefully matched to the biology and stage of the tumor. More sensitive definitions of failure have prompted radiation oncologists and urologists to carefully evaluate the efficacy of external beam irradiation and surgery. Accurate comparison of the efficacy of brachytherapy to surgery and to external beam radiation requires a randomized study. Comparisons of retrospective studies are fraught with the problems of the heterogeneous nature of early-stage prostate cancer. Imbalances in stage, grade, initial PSA extraprostatic disease, and nodal status of patient groups make comparisons difficult. Most of the long-term data for permanent seed implantation are the result of work at a single institution. These results will need to be repeated at other institutions treating patients in a similar manner. Because techniques vary from institution to institution, permanent implant results will need to be carefully evaluated for technique as well as stratified for pretreatment variables. Pretreatment PSA and grade appear to be more sensitive variables than stage in predicting failure after radiation. As more patients are diagnosed with very early and nonpalpable disease, future studies will need to stratify patients based on these pretreatment factors. Patients with early-stage disease but identified as high risk for extraprostatic disease will require more intensive regimens. The treatment outcomes based on biopsy results are inconclusive. A lack of consensus on the definition of a truly positive biopsy remains forthcoming. The value of a positive prostate biopsy as an outcome predictor for clinical failure is still unclear. The use of prostate nuclear cell antigen staining may help clarify the issue. Comparison of treatment outcome based on absolute PSA is also difficult. The Seattle series suggest that brachytherapy by permanent seed implantation is as efficacious as external beam irradiation for early-stage disease in patients with a low PSA (< 10 ng/mL). As the PSA value rises above 10 ng/mL, the probability of failure after external beam rises substantially. Results from the Seattle series suggest an advantage to seed implant alone or the judicious application of seed implant boost to external beam radiation for these patients with more advanced cancer. The most sensitive measurement of therapeutic outcome is progression-free survival. Few studies to date have evaluated progression-free survival.
Biopsy↗
Prostate brachytherapy: importance of technique.
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Brachytherapy↗
Prostate specific antigen based disease control following ultrasound guided 125iodine implantation for stage T1/T2 prostatic carcinoma.
PURPOSE: We report the prostate specific antigen (PSA) based recurrence-free survival rate after 125iodine (125I) implantation for early stage prostatic carcinoma. MATERIALS AND METHODS: A total of 197 patients with clinical stage T1 and T2 prostatic carcinoma underwent outpatient 125I seed implantation. Followup was 1 to 7 years (median 3). Pretreatment serum PSA levels were elevated (greater than 4.0 ng./ml.) in 138 patients (70%). There were 105 well differentiated (Gleason score 2 to 4), 87 moderately differentiated (Gleason score 5 to 6) and 5 indeterminate tumors. The prescribed minimum prostatic dose was 160 Gy. The total dosage of 125I implanted ranged from 15 to 62 mCi. (median 37). Staging lymph node dissection and seminal vesicle biopsies were not routinely performed. RESULTS: Among 138 patients with an elevated PSA level before implantation and no prior hormonal treatment, the PSA value returned to normal in 98% and decreased to less than 1.0 ng./ml. in 82% within 24 months of treatment. In 97% of those 138 patients the PSA level decreased to less than 1.0 ng./ml. at 48 months after implantation. Of 8 patients with an increasing PSA value 5 also had clinically evident failure. The actuarial rate of chemical (increasing PSA) or clinical failure at 5 years following implantation was 7%, with 15 patients still at risk at 5 years. There was a trend for higher failure rates among patients with higher pretreatment PSA levels (p = 0.57), Gleason scores 5 and 6 versus 2 to 4 (p = 0.51) or higher stage of disease (p = 0.17). CONCLUSIONS: There is a high rate of clinical and chemical freedom from progression following 125I implantation for select patients with early stage prostatic carcinoma.
Aged↗
Consensus guidelines for high dose rate remote brachytherapy in cervical, endometrial, and endobronchial tumors. Clinical Research Committee, American Endocurietherapy Society.
PURPOSE: A large number of medical centers have recently instituted the use of High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in treatment regimens, techniques, and dosimetry being used and there are no national standard protocols or guidelines for optimal therapy. METHODS AND MATERIALS: The Clinical Research Committee (CRC) of the American Endocurietherapy Society (AES) met to formulate consensus guidelines for HDRAB in cervical, endometrial, and endobronchial tumors. CONCLUSION: Each center is encouraged to follow a consistent treatment policy in a controlled fashion with complete documentation of treatment parameters and outcome including efficacy and morbidity. Until further clinical data becomes available, the linear quadratic model can be used as a guideline to formulate a new HDR regimen exercising caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The treatments should be fractionated as much as practical to minimize long term morbidity. As more clinical data becomes available, the guidelines will mature and be updated by the Clinical Research Committee of the AES.
Brachytherapy↗
Transperineal ultrasound-guided implantation of the prostate: morbidity and complications.
Two hundred and seventy four patients with early carcinoma of the prostate were treated by ultrasound-guided transperineal I-125 implantation. One hundred and ninety six received implant alone, and 78 were treated with combined external beam and I-125 implantation. Operative, early and late complications were reviewed with a median follow-up time of 40 months (minimum 13, maximum 64 months). Operative complications were negligible. Early morbidity (less than 12 months post implant) was noted in 10-15% of patients and consisted of self-limited irritative uropathy or obstruction. Late complications (more than 12 months post implant) were noted in 13%. Seven percent of patients had some combination of permanent sequelae of treatment: 14 patients had some degree of incontinence, 17 had irritative uropathy symptoms, and 7 had proctitis, 5 of whom resolved spontaneously. Most complications were mild to moderate with a notable absence of severe problems. Urinary morbidity was strongly related to prior or post-implant transurethral resection of the prostate (TURP) (24% with TURP, 3% without). Transperineal implantation in our experience is associated with an acceptable acute and chronic complication rate.
Brachytherapy↗
Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study.
The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.
Antineoplastic Combined Chemotherapy Protocols↗
Salvage therapy with whole-abdominal irradiation in patients with advanced carcinoma of the ovary previously treated by combination chemotherapy.
Whole-abdominal irradiation was delivered to 22 patients with epithelial carcinoma of the ovary who had persistent disease after chemotherapy. Seventeen patients were treated with an open whole-abdominal field and 5 with the moving-field technique. Eleven of the 22 also received a pelvic boost. Two of nine patients with microscopic disease at second look are alive and disease-free at 34 and 52 months, respectively. There were no salvages among the patient with macroscopic disease. Major complications included bowel obstruction in three patients and radiation enteritis in one patient. Whole-abdominal irradiation is not an effective salvage regimen after multiagent chemotherapy.
Abdomen↗
Fast neutron teletherapy for advanced carcinomas of the oral cavity and soft palate.
A retrospective study was performed to determine the efficacy of using fast neutron radiation for treating advanced squamous cell carcinomas of the oral cavity and soft palate. The majority of patients were judged to have less than a 10% 5-year survival with conventional medical treatment. Fifteen patients with oral cavity tumors were treated for cure with neutrons alone and six were treated with a combination of neutrons and photons as part of a mixed beam fractionation scheme. In the neutron-only group, the complete regression rate was 33% in the mixed beam group, the rate was 50%. Five patients who had squamous cell carcinomas of the soft palate were treated for cure, one with neutrons alone and four with a mixed beam regimen. The complete regression rate was 100%. The two-year NED results are comparable with literature results for more selected groups of patients with oral cavity and soft palate tumors treated by conventional photon therapy. The acute treatment morbidity was perhaps somewhat greater in the subgroup of patients treated with neutrons alone, and this subgroup later developed a more pronounced subcutaneous fibrosis. Morbidity associated with the mixed beam treatment regimen was comparable to that associated with conventional radiotherapy.
Carcinoma, Squamous Cell↗
Solitary plasmacytoma of bone and soft tissues.
Between 1956 and 1978, nine patients with solitary plasmacytoma of bone (SPB) and seven with extramedullary plasmacytoma (EMP) were treated at the University of Washington Hospital and Swedish Tumor Institute. All but one patient had local radiotherapy. In the SPB group, six of nine patients progressed to multiple myeloma (MM) and five died of disease within three years after dissemination. Three of the nine patients are alive at 5, 8, and 16 years, respectively. In the EMP group, none of the seven patients progressed to MM. Five are alive 16 months to 23 years after radiotherapy. Since there are no reliable criteria for prospectively distinguishing true solitary plasmacytoma from occult MM, all patients with apparently isolated plasmacytoma should receive local radiotherapy with curative intent.
Adult↗
Cystic cerebellar astrocytomas in childhood.
Thirty-nine patients with low grade cystic cerebellar astrocytomas were treated at the University of Washington and Children's Orthopedic Hospital in Seattle, Washington, between 1955 and 1977; 29 were treated with partial or complete resection alone, and 10 received radiation therapy after various types of surgical procedures. With a mean follow-up time of 7 years, the survival rate for patients who had complete resections of their primary disease was 100%. The relapse-free survival rate was 82%. The relapse-free survival rate for patients treated primarily with partial resection alone was 36%. Postoperative irradiation after partial resection for both primary and recurrent disease resulted in a relapse-free survival rate of 83%. If complete tumor excision is not possible, postoperative radiation therapy is recommended following partial resection.
Adolescent↗
Evaluation of fast neutron teletherapy for advanced carcinomas of the major salivary glands.
This review analyzes the local control rate of fast neutron beam teletherapy for malignant salivary gland carcinomas compared to conventional photon irradiation at the same institution. Thirty patients with malignant parotid or submaxillary gland tumors were treated with either cobalt-60 (19 patients) or neutrons +/- photons (11 patients). The 19 photon-treated patients were historical controls. No advantage is found for neutrons in patients with tumors less than 3 cm where 100% local control was achieved with either modality. In patients with tumor masses 3-6 cm in size, neutrons demonstrated a possible advantage with a local control rate of 100% (followup, 7-18 months) compared to a control rate of 33% with conventional photon irradiation. Acute treatment-related morbidity was slightly greater in neutron-treated patients, but no long-term complications have been observed to date.
Evaluation Studies as Topic↗
Fast neutron teletherapy for advanced carcinomas of the oropharynx.
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Adult↗
Complications of combined surgery and neutron radiation therapy in patients with advanced carcinoma of the head and neck.
A total of 135 patients with advanced squamous-cell carcinoma of the head and neck were treated with cyclotron-generated fast neutrons. Thirty-eight had major surgery before or after irradiation. Major complications (fistula formation, carotid artery exposure or blowout requiring ligation, or major wound breakdown) occurred in 37%. The complication rates associated with surgery prior to irradiation, planned surgery following irradiation, and salvage surgery following irradiation were 0/12, 4/5, and 10/21, respectively. The complication rate for surgery following neutron irradiation alone was 73%; for surgery following mixed-beam irradiation it was 20%. The age of the patient and the interval between surgery and irradiation had no influence on the complication rate.
Carcinoma, Squamous Cell↗
The role of radiation therapy in the treatment of glomus jugulare tumors.
The records of 14 patients who received irradiation for incompletely excised, inoperable or recurrent glomus jugulare tumors were retrospectively reviewed. Ages ranged from 12 to 66 years, and the male to female ratio was 1:3. With a follow-up time of 1.3 to 17.2 years (mean of 7.7 years), 11/14 remain clinically disease-free. Doses of at least 4000 rad are shown to be effective in controlling glomus jugular tumors.
Adolescent↗