Biomedical subjects

M A Lockett

Publications and source records attributed to M A Lockett.

At least 37 records · Page 2Linked to original sources

PubMed1997

Cost benefit of emerging technology in localized carcinoma of the prostate.

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.

Adenocarcinoma↗

PubMed1997

Postoperative radiation therapy in non-small cell lung cancer.

One hundred seventy-three patients with the diagnosis of non-small cell lung cancer (NSCLC) were treated with surgery and postoperative radiation therapy (RT) at the Radiation Oncology Center, Washington University, St. Louis. All patients had been retrospectively reviewed and restaged according to the new American Joint Committee (AJC) staging classification. Seventeen patients were stage I, 69 were stage II, 74 were stage IIIA, and 2 patients were stage IIIB. In 11 patients, accurate staging could not be determined. Indications for postoperative RT were positive surgical margins (32 patients), metastatic hilar nodes (78 patients), and metastatic mediastinal nodes (62 patients). Locoregional control for stages I, II, and IIIA was 85, 75, and 85%, respectively. Five-year actuarial survival was 35% for stage I and 20% for stages II and IIIA. Patients with N0 disease (positive margins) had 5-year survival of 25%, whereas patients with N1 and N2 disease had a 5-year survival of 20%.

Adenocarcinoma↗

PubMed1996

Nonrandomized evaluation of pelvic lymph node irradiation in localized carcinoma of the prostate.

PURPOSE: A great deal of controversy exists regarding the potential benefit of pelvic lymph node irradiation compared with treatment to the prostate only in patients with localized prostate cancer. Despite numerous reports, including a randomized study, this issue has not been completely elucidated. METHODS AND MATERIALS: A total of 963 patients with histologically proven localized adenocarcinoma of the prostate treated with definitive radiation therapy alone were analyzed. Median follow-up was 6.5 years (minimum: 2 years, maximum: 22 years). Pelvic lymph nodes received 40 to 55 Gy with anteroposterior/posteroanterior and sometimes lateral stationary portals in 1.8 Gy daily fractions; an additional dose was delivered to the prostate with 120 degrees bilateral are rotation to complete doses of 65 to 68 Gy for Stage A2 and B tumors and 68 to 71 Gy for Stage C tumors. The same total doses were delivered with smaller fields when the prostate only was treated. RESULTS: In Stage A2 (T1b,c) the 10-year clinical pelvic failure rate was 16% regardless of the volume irradiated or tumor differentiation. With Stage B (T2) well- or moderately differentiated tumors, the 10-year pelvic failure rates were 22% when pelvic lymph nodes were irradiated and 32% when prostate only was irradiated (p = 0.41). With Stage A2 (T1b,c) and B (T2) poorly differentiated tumors, the 10-year pelvic failure rates were 32% and 7%, respectively (p = 0.72). With clinical stage C (T3) well-differentiated tumors treated with 50 to 55 Gy to pelvic lymph nodes, the pelvic failure rate was 22% compared with 37% in those receiving 40 to 45 Gy (p < or = 0.07). A significant reduction in pelvic failures was noted with Stage C poorly differentiated tumors when the pelvic lymph nodes received doses higher than 50 Gy (23%) compared with lower doses (46%) (p < or = 0.01). Volume or doses of irradiation did not influence incidence of distant metastases in any stage or tumor differentiation group. Disease-free survival did not correlate with volume treated in any clinical stage or tumor differentiation group. In 317 patients on whom pretreatment prostate-specific antigen levels were available, there is a suggestion that those treated to the pelvic lymph nodes had a higher chemical disease-free survival than those receiving prostate irradiation only. Follow-up is short, and differences are not statistically significant in any of the groups. Morbidity of therapy was slightly higher in patients treated to the pelvic lymph nodes, but in Stages A2 (T1b,c) and B (T2) differences are not statistically significant (4 to 6%). Stage C patients treated to the pelvic lymph nodes with 50 Gy had a 12% incidence of Grade 2 rectosigmoid morbidity compared with 6% in those treated with 40 Gy (p = 0.26). CONCLUSIONS: In this retrospective analysis, pelvic lymph node irradiation did not influence local/pelvic tumor control, incidence of distant metastases, or disease-free survival in patients with clinical Stage A2 (T1b,c) or B (T2) localized carcinoma of the prostate. In patients with Stage C (T3) disease, irradiation of the pelvic lymph nodes with doses of 50 to 55 Gy resulted in a lower incidence of pelvic recurrences and improved disease-free survival. Morbidity of therapy was acceptable, although patients with Stage C disease had a somewhat higher incidence of Grade 2 rectosigmoid morbidity. Pelvic lymph node irradiation is being elucidated in properly designed prospective, randomized protocols.

Adenocarcinoma↗

PubMed1996

Brachytherapy or electron beam boost in conservation therapy of carcinoma of the breast: a nonrandomized comparison.

PURPOSE: The results of breast-conservation therapy using breast irradiation and a boost to the tumor excision site with either electron beam or interstitial 192Ir implant are reviewed. METHODS AND MATERIALS: A total of 701 patients with histologically confirmed Stage T1 and T2 carcinoma of the breast were treated with wide local tumor excision or quadrantectomy and breast irradiation. The breast was treated with tangential fields using 4 or 6 MV photons to deliver 48 to 50 Gy in 1.8 to 2 Gy daily dose, in five weekly fractions. In 80 patients the regional lymphatics were irradiated. In 342 patients with Stage T1 and 107 with Stage T2 tumors, boost to the primary tumor excision site was delivered with 9 MeV and, more frequently, with 12 MeV electrons. In 91 patients with Stage T1 and 38 patients with Stage T2 tumors an interstitial 192Ir implant was performed. Tumor control, disease-free survival, cosmesis, and morbidity of therapy are reviewed. Minimum follow-up is 4 years (median 5.6 years; maximum, 24 years). RESULTS: The overall local tumor recurrence rates were 5% in the T1 and 11% in the T2 tumor groups. There was no significant difference in the breast relapse rate in patients treated with either electron beam or interstitial 192Ir boost. Regional lymph node recurrences were 1% in patients with T1 and 5% with T2 tumors. Distant metastases were recorded in 5% of the T1 and 23% of the T2 groups. The 10-year actuarial disease-free survival rates were 87% for patients with T1 and 75% with T2 tumors. Disease-free survival was exactly the same in patients receiving either electron beam or interstitial 192Ir boost. Cosmesis was rated as excellent/good in 84% of patients with T1 tumors treated with electron beam and 81% of patients treated with interstitial implant, and 74 and 79% respectively, in patients with T2 tumors. CONCLUSIONS: Breast-conservation therapy is an effective treatment for patients with T1 and T2 carcinoma of the breast. There is no difference in local tumor control, disease-free survival, cosmesis, or morbidity in patients treated with either electron beam or interstitial 192Ir implant boost. Clinical trials in progress will further elucidate this controversial subject.

Brachytherapy↗

PubMed1996

Carcinoma of the uterine cervix. II. Lack of impact of prolongation of overall treatment time on morbidity of radiation therapy.

PURPOSE: Several reports document a negative impact of prolongation of overall treatment time in a course of irradiation on tumor control and survival. A correlation has been documented of incidence of significant treatment sequelae with increasing doses of irradiation, volume of the specific organ, and dose per fraction. However, no data were found on the potential correlation of overall irradiation treatment time with significant sequelae. METHODS AND MATERIALS: Records were reviewed of 1,269 patients with carcinoma of the cervix (Stage IB to HI) treated with definitive irradiation (combination of external beam and two intracavitary insertions). Follow-up was obtained in 97% of patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationships between overall treatment time and time of brachytherapy and incidence of treatment sequelae were analyzed for each stage. RESULTS: Overall incidence of Grades 2 (moderate) sequelae was 7% and of Grade 3 (severe) sequelae, 11%. There was no significant correlation of various incidences of Grade 2 and 3 sequelae with overall treatment times (8% in patients treated in less than 7 weeks, 9% in 7.1 to 9 weeks, and 12% when treatment time was longer than 9 weeks) (p = 0.08). In patients with Stage IB and IIA tumors, incidence of rectal toxicity (mostly proctitis) was comparable in patients treated in less than 7 or 7.1 to 9 weeks (4.1 and 6%, respectively) and slightly higher in those treated in longer periods (11.5%) (p = 0.24). In patients with Stage IIB and III, the incidence of Grade 2 and 3 small bowel morbidity was 2% in those treated in less than 7 weeks, 6% for 7.1 to 9 weeks, and 4.9% for longer times (p < or = 0.01). This increased morbidity was also correlated with total dose of irradiation to the lateral pelvic wall: 5 of 257 (2%) for less than 60 Gy and 21 of 438 (4.8%) for higher doses (p < or = 0.01). There was no significant correlation between the timing of brachytherapy (usually two low dose rate intracavitary insertions performed within 4.5 to 6.5 weeks of initiation of external beam therapy) and significant treatment sequelae. CONCLUSIONS: We observed a varied average incidence of Grade 2 and 3 morbidity in the bladder, rectum, and small intestine with different overall treatment times, without a definite pattern to suggest an impact of prolongation of treatment time on morbidity. Likewise, there was no significant correlation with the timing of intracavitary insertions and morbidity of therapy. Because prolongation of the overall treatment time has a well-documented detrimental effect on pelvic tumor control and survival in carcinoma of the cervix with no significant impact on morbidity, it is imperative to deliver radiation therapy in the shortest possible time and without schedule interruptions.

Aged↗

PubMed1995

Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy.

PURPOSE: Some studies have described decreased pelvic tumor control and survival rates in invasive carcinoma of uterine cervix when the overall time in a course of definitive irradiation is prolonged. We attempt to confirm or deny these observations and evaluate the impact of timing of brachytherapy on outcome. We also explore the hypothesis that more extensive tumors technically require prolongation of the course of irradiation; thus, decreased tumor control and survival in these patients may not necessarily be the result of time/dose factor. METHODS AND MATERIALS: Records of 1,224 patients (Stage IB to III) treated with definitive irradiation (combination of external beam and two intracavitary insertions to deliver doses of 70 to 90 Gy to point A) were reviewed. Follow-up was obtained in 97% of the patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationship between outcome and overall treatment time and time of intracavitary insertions was analyzed in each stage and according to tumor size/extent. RESULTS: There was strong correlation between overall treatment time (OTT) and tumor stage (< or = 7 weeks: 81% for Stage IB; 74% for Stage IIA; 52% for Stage IIB; and 47% for Stage III). Interruptions of therapy accounting for prolongation of treatment time occurred in 25-30% of patients, most frequently because of holidays and weekends and side effects of therapy. Overall treatment time had a major impact on pelvic tumor control in Stages IB, IIA, and IIB; in Stage IB 10-year actuarial pelvic failure rates were 7% with OTT < or = 7 weeks, 22% with 7.1 to 9 weeks, and 36% with > 9 weeks (p < or = 0.01). For Stage IIA the corresponding values were 14%, 27%, and 36% (p = 0.08), and in Stage IIB pelvic failure rates were 20%, 28%, and 34%, respectively (p = 0.09). In Stage III, pelvic failure was 30%, 40%, and 50%, respectively (p = 0.08). There was also a strong correlation between OTT and 10-year cause-specific survival (CSS); in Stage IB rates were 86% with OTT of < or = 7 weeks, 78% for 7.1 to 9 weeks, and 55% for > or = 9 weeks (p < 0.01). The corresponding rates in Stage IIA were 73%, 41%, and 48% (p < or = 0.01). For patients with Stage IIB, CSS rates were 72% for OTT < or = 7 weeks, 60% for 7.1 to 9 weeks, and 70% for > 9 weeks (p = 0.01). Patients with Stage III disease had 45% 10-year CSS when treatment was delivered in 9 weeks or less and 36% for longer overall times (p = 0.16). In multivariate analysis of patients with Stage IB and IIA, OTT and clinical stage were the most important prognostic factors for pelvic tumor control, disease-free survival, and CSS. Tumor size was a prognostic factor for CSS. In Stages IIB and III, OTT, clinical stage, unilateral or bilateral parametrial invasion, and dose to point A were significant prognostic factors for pelvic tumor control, disease-free survival, and CSS. Prolongation of time had a significant impact on pelvic tumor control and CSS regardless of tumor size, except in Stage IB tumors < or = 3 cm. Regression analysis confirms previous reports that prolongation of OTT results in decreased pelvic tumor control rate of 0.85% per day for all patients, 0.37% per day in Stages IB and IIA, 0.68% per day in Stage IIB, and 0.54% for Stage III patients treated with > or = 85 Gy to point A. Performance of all intracavitary insertions within 4.5 weeks from initiation of irradiation yielded decreased pelvic failure rates in some groups of patients (8.8 vs. 18% in Stage IB and IIA tumors < or = 4 cm and 12.3 vs. 35% in Stage IIB) (p < or = 0.01). CONCLUSIONS: Prolongation of treatment time in patients with Stage IB, IIA, IIB, and III carcinoma of the uterine cervix has a significant impact on pelvic tumor control and CSS. The effect of OTT was present regardless of tumor size except in Stage IB tumors < or = 3 cm.

Actuarial Analysis↗

PubMed1995

Adjuvant radiation therapy for rectal carcinoma: predictors of outcome.

PURPOSE: To review predictors of outcome, including sequencing of modalities and pretreatment findings for adjuvantly treated rectal cancer. METHODS AND MATERIALS: From 1975 through 1990, 307 patients with adenocarcinoma of the rectum underwent adjuvant radiation therapy. In 251 cases the radiation therapy was administered preoperatively, either 40-50 Gy (median dose 45 Gy) followed in 6-7 weeks by surgery (210 cases), or 20 Gy in five fractions immediately prior to surgery (41 cases). In 56 cases, patients were referred postoperatively for radiation (median dose 50 Gy). Adjuvant chemotherapy was never given concurrently with the preoperative radiation (RT), although 43 of the cases (including 14 of the preoperative RT cases) received postoperative chemotherapy. RESULTS: Multivariate analysis (Cox model) indicated that significant predictors of better overall freedom from disease were preoperative rather than postoperative RT (p < 0.001), low surgical stage (p < 0.0001), specialist surgeon (p = 0.007), low or moderate histologic grade (p = 0.026), and proximal lesion (p = 0.033). The significant predictors for better local control included use of preoperative RT (p < 0.001), low or moderate grade (p = 0.001), and low surgical stage (p = 0.015). The 5-year local control and freedom from disease for the preoperative RT patients were 90% +/- 2% and 73% +/- 3%, respectively. The selected cases that received the short course of 20 Gy preoperatively did well. Although 24 out of 41 patients proved to have Astler Coller B2 or C disease, local control at last follow-up was 39 out of 41 (95%). A second multivariate analysis of pretreatment factors was performed on the preoperative RT cases. The significant factors for both local control and overall freedom from disease were noncircumferential vs. circumferential tumor, proximal vs. distal lesion, and background of the surgeon. Additional negative factors on univariate analysis (although not achieving independent significance on multivariate analysis) included the finding of near-obstructing lesions and elevated carcinoembryonic antigen (CEA). Grade > or = 3 sequelae occurred in 8% of cases (including 3% bowel obstruction). The only significant factor for complications was background of the surgeon (4% for colorectal specialists vs. 12% for nonspecialists, p = 0.015). CONCLUSIONS: Significant factors for better tumor control included preoperative as opposed to postoperative RT and the experience of the surgeon. In selected cases, excellent results can be obtained with a short course of preoperative radiation. Concurrent chemotherapy need not be given routinely with preoperative radiation. Subgroups of preoperative RT cases at risk for distant metastases (who might benefit from postoperative chemotherapy), and at high risk for local failure (for whom concurrent preoperative chemotherapy and radiation might be considered), are identified.

Adenocarcinoma↗

PubMed1995

Irradiation alone or combined with surgery in stage IB, IIA, and IIB carcinoma of uterine cervix: update of a nonrandomized comparison.

PURPOSE: Definitive radiation therapy alone or combined with surgery in carcinoma of the uterine cervix yields comparable tumor control and survival in Stages I and IIA when patients are adequately treated with either modality. Our 30-year institutional experience is described. METHODS AND MATERIALS: This is a nonrandomized comparison of treatment results of 415 patients with Stage IB, 137 with Stage IIA, and 340 with Stage IIB carcinoma of the uterine cervix treated with irradiation alone and 197 with Stage IB, 44 with Stage IIA, and 65 with limited Stage IIB treated with pre- or postoperative irradiation and surgery. Irradiation alone consisted of a combination of external beam therapy and intracavitary insertions to deliver doses of 70 to 85 Gy to point A for patients with Stages IB and IIA disease and 80 to 90 Gy for patients with bulky or Stage IIB tumors. For patients treated with irradiation and surgery, various combinations of external beam and intracavitary therapy were used to deliver 60 to 75 Gy to point A. Surgical procedures consisted of radical hysterectomy with or without lymph node dissection in 130 patients with Stage IB, 28 patients with Stage IIA, and 10 patients with limited Stage IIB. Fifty-seven patients had total abdominal or conservative hysterectomy with or without lymph node dissection, and 3 had vaginal hysterectomy. In addition, 51 patients with Stage IIB tumors underwent pelvic lymphadenectomy after definitive irradiation. RESULTS: The 5-year cause-specific survival (CSS) rates for patients with Stage IB nonbulky tumors treated with irradiation alone or irradiation combined with surgery were 90 and 85%, respectively, and the 10-year survival rate was 84% with either modality. In patients with bulky tumors (> 5 cm), the 5-year CSS rates were 61% with irradiation alone and 63% with irradiation plus surgery; at 10 years the rates were 61 and 68%, respectively (p = 0.5). For those with Stage IIA nonbulky tumors, the 5-year CSS rates were 75% with irradiation alone and 83% with combined irradiation and surgery, and 10-year CSS rates were 66 and 71%, respectively. In patients with Stage IIA bulky tumors, the 5-year CSS rates were 69% with irradiation alone and 60% with irradiation plus surgery, and at 10 years, 69 and 44%, respectively (p = 0.05). In patients with Stage IIB nonbulky tumors treated with irradiation alone or combined with surgery, the 5- and 10-year CCS rates were 72 and 65%, respectively; the corresponding survival rates with bulky tumors or bilateral parametrial involvement were 56 and 50%. Incidence of pelvic failures, alone or with distant metastasis, for Stage IB was 10% (43 out of 415) with irradiation alone and 14% (28 of 197) with irradiation plus surgery; for Stage IIA, 17% (23 out of 137) with irradiation alone and 20% (9 our of 44) with irradiation plus surgery; and for Stage IIB, 23% (88 out of 391) with irradiation alone and 29% (4 out of 14) with irradiation plus surgery. Grade 3 sequelae were comparable in both groups (irradiation alone, 5% to 11%; irradiation combined with surgery, 8% to 12%); the differences are not statistically significant. The most frequent major sequelae in 892 patients receiving irradiation only were rectovaginal fistula (13 cases, 1.5%), proctitis (10, 1.1%), small bowel obstruction (16, 1.8%), ureteral stricture (16, 1.8%), and vesicovaginal fistula (8, 0.9%). In 306 patients treated with irradiation plus surgery, the most commonly recorded major sequelae were small bowel obstruction/perforation (13 cases, 4.2%), ureteral stricture (8, 2.6%), vesicovaginal fistula (5, 1.6%), and rectovaginal fistula (4, 1.3%). CONCLUSION: Irradiation alone or combined with surgery yields comparable pelvic tumor control, survival, and morbidity in patients with Stage IB, IIA, and limited IIB carcinoma of the uterine cervix.

Carcinoma↗

PubMed1995

Radiation therapy in the treatment of localized prostate cancer: an alternative to an emerging consensus.

Optimal treatment for patients with localized carcinoma of prostate is controversial. Radiation therapy is an established modality; reports indicate that results are comparable to those of radical prostatectomy. A retrospective review was carried out of 963 patients with carcinoma of the prostate treated with definitive irradiation (65 to 71 Gy in 6.5 to 7 weeks). Survival, incidence of local recurrence and distant metastases, and postirradiation PSA data were analyzed. Ten-year disease-free survival with external irradiation was 100% for clinical stage A1 (T1a), 69% for stage A2 (T1b,c), 57% for clinical stage B (T2), and 41% for stage C (T3). Initial PSA level closely correlated with probability of freedom from chemical failure (PSA elevation) after definitive irradiation in 317 patients with stage T1b,c and T2 tumors (96% and 89%, respectively, with initial PSA of < 10 ng/ml and 75% and 65% with higher PSA levels). Although modern irradiation techniques produce results comparable to those of radical prostatectomy in localized prostate carcinoma, we must continue to critically assess treatment policies, develop appropriately designed prospective clinical trials, and define optimal management of these patients.

Disease-Free Survival↗

PubMed1994

Management of locally advanced carcinoma of the breast. II. Inflammatory carcinoma.

BACKGROUND: Inflammatory carcinoma of the breast has been associated with a poor prognosis. Several therapeutic approaches have been under investigation in an effort to improve outcome. METHODS: This is a retrospective analysis of 179 patients with histologically confirmed inflammatory carcinoma of the breast: 33 treated with irradiation alone, 35 with combined irradiation and chemotherapy, 25 with irradiation and surgery, and 86 with a combination of three modalities. RESULTS: The 5-year disease free survival (DFS) rates were 40% for patients treated with three modalities, 24% for those treated with irradiation and surgery, and 6% for those treated with irradiation alone or in combination with chemotherapy without a surgical procedure. The 10-year DFS rates were 35%, 24%, and 0%, respectively. Cause specific survival (CSS) curves closely follow the same trends. A clearly superior locoregional tumor control was observed in patients who underwent a surgical procedure: 79% with three modalities, 76% with irradiation and surgery, and only 30% with irradiation alone or in combination with chemotherapy. Distant metastasis occurred in 57% of the group treated with triple-modality therapy, 60% of those treated with irradiation plus surgery, and 85% of the patients treated with irradiation alone or in combination with chemotherapy. There was no significant correlation between the type of mastectomy or doses of irradiation and locoregional tumor control or survival. The significant morbidity of the trimodal therapy (10%), although somewhat higher than that of other modalities (3.2%), was acceptable. CONCLUSIONS: The addition of mastectomy to irradiation significantly improved locoregional tumor control, DFS, and CSS; differences were statistically significant. The combination of chemotherapy, surgery, and irradiation had a significant impact on locoregional tumor control and incidence of distant metastases compared with surgery plus irradiation, and a lesser impact, although still statistically significant, on DFS and CSS. Further clinical trials are needed to optimize the management of patients with inflammatory breast cancer.

Adenocarcinoma↗

PubMed1994

Technical factors affecting morbidity in definitive irradiation for localized carcinoma of the prostate.

PURPOSE: The impact of some technical factors on morbidity was analyzed in 738 patients with histologically confirmed carcinoma of the prostate treated with definitive irradiation. METHODS AND MATERIALS: The records of all patients were reviewed, and morbidity of irradiation was evaluated according to severity. All patients were followed up for a minimum of 3 years (median observation, 6.5 years). RESULTS: The most frequent Grade 2 (moderate) intestinal complication was proctitis, which was observed in 5% of the patients, followed by enteritis (1%) and anal-rectal fibrosis or stricture (about 1%). Incidence of Grade 3 (severe) proctitis was less than 1% and small bowel obstruction, 0.2%. One patient developed radiation-induced ileitis complicated with peritonitis, which was fatal. The most frequent Grade 2 urinary complication was urethral stricture (5%) and cystitis with significant symptoms or hematuria (2%). A vesicosigmoid and a rectovesical fistula (.4%) were noted, which required colostomy. One patient with hemorrhagic cystitis (.2%) required an ileal bladder, and two cases of ureteral stricture (.3%) required surgical correction. Most cases of Grade 2-3 intestinal or urinary morbidity appeared within 2-5 years after therapy (8% moderate and 3% severe cumulative intestinal morbidity at 10 years, and 9% and 3%, urinary). The actuarial incidence of rectosigmoid Grade 2 and 3 morbidity was 10% for patients treated to the pelvic lymph nodes and the prostate and 3% for those treated to the prostate only (p = 0.04). The difference in urinary morbidity in these two groups of patients was not statistically significant. There was also no significant correlation of morbidity with boost portal size for prostate irradiation. Patients treated with a stationary portal technique that delivered higher doses to the urinary bladder had a significantly greater incidence of urinary morbidity (18% cumulative) compared with patients treated with rotational techniques (5%) (p < 0.1). However, patients treated with pelvic fields and rotational techniques had a higher intestinal and rectosigmoid morbidity (11%) than patients treated to the prostate only (< or = 5%) (p = 0.05). No statistically significant difference in intestinal or urinary morbidity was related to doses of irradiation (60-70 Gy). CONCLUSION: Volume treated and, to a lesser extent, dose of irradiation at tolerance levels are important factors influencing significant morbidity in patients with carcinoma of the prostate treated with definitive irradiation. With recent advances in three-dimensional (3-D) treatment planning and conformal radiation therapy techniques, it is imperative to precisely determine optimal volumes and doses of irradiation required to achieve the highest local-pelvic tumor control while minimizing morbidity to enhance the role of irradiation in the management of localized carcinoma of the prostate.

Adenocarcinoma↗

PubMed1994

Adjuvant irradiation after prostatectomy for carcinoma of the prostate with positive surgical margins.

BACKGROUND: Patients with adenocarcinoma of the prostate treated with prostatectomy who have tumor at the margins of the surgical specimen or tumor involvement of the seminal vesicles have a high risk of local recurrence and metastatic disease. It is unclear whether postoperative irradiation improves their outcome. METHODS: This is a retrospective analysis of patients treated with prostatectomy for adenocarcinoma of the prostate who had surgical margins or seminal vesicles involved by tumor. Thirty-four patients received adjuvant postoperative irradiation (Group 1), and 43 patients did not receive irradiation (Group 2). RESULTS: The tumor control rates in the prostatic bed for patients who had radical prostatectomy were 100% and 84% in Groups 1 and 2, respectively (P = 0.017). Actuarial 10-year disease-free survival from the date of prostatectomy was 46% and 55% for Groups 1 and 2, respectively. CONCLUSIONS: Adjuvant irradiation after prostatectomy in patients with positive surgical margins or seminal vesical invasion increases prostatic bed local tumor control but does not affect survival. Postoperative irradiation is associated with acceptable morbidity.

Adenocarcinoma↗

PubMed1993

Technical and tumor-related factors affecting outcome of definitive irradiation for localized carcinoma of the prostate.

PURPOSE: The influence of some tumor-related and technical factors on therapeutic outcome is analyzed in 738 patients with histologically confirmed carcinoma of the prostate treated with definitive irradiation. METHODS AND MATERIALS: This is a retrospective study of the records of the Radiation Oncology Center. The information was coded on computer-compatible forms and analyzed with multiple cross-reference checks to ensure data reliability. Detailed analysis of portal films and dose distribution isodose curves was carried out in 310 patients on whom this information was readily available. All patients were followed-up for a minimum of 3 years (median observation, 6.5 years). RESULTS: Disease-free survival rates in Stages A2 (T1b) and B (T2) were 76% at 5 years and 62% at 10 years; in Stage C (T3) it was 57% at 5 years and 38% at 10 years. Overall, prostate recurrence rates were: 8% for Stage A2, 17% for Stage B, 28% for Stage C, and 46% for Stage D1 (T4). The 10-year actuarial local failure rate by stage was 20% in Stage A2 (T1b), 24% in Stage B (T2), 40% in Stage C (T3), and 70% in Stage D1 (T4) tumors. When the inferior margin of the portals was at or caudal to the ischial tuberosity, the actuarial 5-year pelvic failure rate was 0% for Stage A2 (T1b), 18% for Stage B (T2), and 20% for Stage C (T3), in contrast to 60% for Stage A2 (T1b), 27% for Stage B (T2), and 38% for Stage C (T3) when the inferior margin was cephalad to the ischial tuberosity (p = 0.05 in Stage C). Local tumor control was comparable in Stages A2 (T1b) and B (T2) when either small fields limited to the prostate and periprostatic tissues were used or, in addition, the pelvic lymph nodes were irradiated (85% and 80%, respectively). In Stage C (T3) there was significantly better pelvic tumor control (80% of 274 patients) when all of the pelvic (including common iliac) lymph nodes were treated compared with 65% in a group of 137 patients on whom the lymph nodes were irradiated with smaller fields (14 x 14 cm) (p = 0.01). In Stage C (T3), 30 patients treated with doses less than 6000 cGy had a 50% overall pelvic failure rate compared with 35% in 20 patients receiving 6500 cGy and 24% in 362 patients treated with 7000 cGy (p = 0.01). Pelvic tumor control or failure was closely associated with development of distant metastasis. In patients with pelvic tumor control, the distant metastasis rate was 18% for stages A2 (T1b) and B (T2) and 30% for stage C (T3), in contrast to 30% (p = 0.02) and 65% (p < 0.01), respectively, when prostate/pelvic failure was detected. CONCLUSION: Volume treated and dose of irradiation are important factors influencing local/pelvic recurrence rate in carcinoma of the prostate, particularly in stage C tumors. With recent advances in three-dimensional treatment planning and conformal radiation therapy techniques, it is imperative to determine optimal volumes and doses of irradiation to be delivered to these patients while minimizing morbidity to enhance the role of irradiation in the management of localized carcinoma of the prostate.

Adenocarcinoma↗

PubMed1993

Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy.

BACKGROUND: This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease. METHODS: Of the patients with primary tumors, 13 were treated with wide local excision plus radiation therapy; 13 had radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes; 8 received similar postoperative radiation therapy after partial or simple vulvectomy; 16 patients had radiation therapy alone after biopsy; and 17 had recurrent tumors treated with radiation therapy alone. RESULTS: In patients treated with biopsy/local excision, local tumor control was 92-100% in T1-3N0 disease, 40% in similar stages with N1-3, and 27% in recurrent tumors. Among patients treated with partial/radical vulvectomy and radiation therapy, primary tumor control was 90% in those with T1-3 tumors and any nodal stage, 33% in those with any T stage and N3 lymph nodes, and 66% in patients with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for patients with T1N0 disease, 62% for those with T2-3N0 disease, 30% for those with T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 disease. Four of 17 patients treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and radiation therapy. In patients with T1-2 tumors treated with biopsy/wide tumor excision and radiation therapy with doses less than 50 Gy, the local tumor control was 75% (three of four patients), in contrast to 100% (13 of 13 patients) with 50.01-65 Gy. With T3-4 tumors treated with local excision and radiation therapy, tumor control occurred in none of three patients with doses less than 50 Gy and 66% (six of nine) with 50.01-65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and radiation therapy, local tumor control was 75% (six of eight), regardless of dose level; in T3-4 tumors, it was 67% (four of six patients) with 50-60 Gy and 86% (six of seven) with 65-70 Gy. Differences were not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes, with doses of 50 Gy being adequate for elective treatment of nonpalpable lymph nodes and 60-70 Gy controlling tumor growth in 75-80% of patients with N2-3 nodes when administered postoperatively, after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Wide local tumor excision and radiation therapy or irradiation alone in T1-2 tumors is an alternative treatment to radical vulvectomy in controlling vulvar carcinoma, with significantly less morbidity. In comparison with reported rates for surgery alone, radiation therapy after radical vulvectomy for locally advanced tumors improves tumor control at the primary site and regional lymphatics. Indications and techniques of radiation therapy are discussed.

Adenocarcinoma↗

PubMed1993

Definitive external irradiation in stages A (T1) and B (T2) carcinoma of the prostate.

This is a retrospective review of records of 38 patients with clinical stage A (T1a,b), 131 with stage B1 (T2a), and 113 with B2 (T2b) histologically proven adenocarcinoma of the prostate treated with definitive irradiation. All patients have been followed for a minimum of 3 years (median follow-up: 6.5 years; maximum: 23 years). Patients were treated with high-energy photons (18-22 MV) with either 4,500 cGy to pelvic fields and a boost of about 2,000 cGy to the prostate or 6,600 cGy to the prostate and periprostatic tissues. Five patients with stage A1 (T1a) tumors had no failures. The local recurrence rate was 11% in stage T1b, 14% in T2a, and 17% in T2b tumors. Distant metastasis rates were 16% in patients with stage T1b, 20% in T2a, and 21% in T2b. The disease-free survival rate was approximately 70% at 5 years and 55% at 10 years in patients with stages T1b or T2, without significant differences among the various groups. The cause-specific survival was 90% at 5 years and 70% at 10 years in the various groups. The results are comparable to those reported in several surgical or radiation therapy series at various institutions. A significantly lower disease-free survival was observed in patients with poorly differentiated tumors (40% at 5 years) in comparison with those with well- and moderately differentiated tumors (80% DFS at 5 years) (p < .001). Likewise, the cause-specific survival was lower in patients with poorly differentiated tumors (75% at 5 years) than in the other patients (91%) (p = .0003). No difference in the local recurrence rates with various degrees of differentiation was noted. However, patients with poorly differentiated tumors had a greater incidence of distant metastasis (30%-40%) than patients with well or moderately differentiated lesions (10%-20%). Performance of transurethral resection also was associated with a higher incidence of distant metastasis (40%) in patients with stage B2 (T2b) tumors than in those diagnosed by needle biopsy (20%) (p = .12) but not in the other groups. Age, race, volume irradiated, or doses of irradiation lower or higher than 6500 cGy did not significantly affect outcome. Radiation therapy is an effective treatment for patients with stage A (T1) or B (T2) carcinoma of the prostate. Careful selection and refinement of treatment techniques, including three-dimensional treatment planning and conformal delivery irradiation or brachytherapy, may improve the management of these patients.

Adenocarcinoma↗

PubMed1992

Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone.

The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow-up time was 3 years. The 10-year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10-year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P less than or equal to 0.01). Five-year disease-free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5-year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10-year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage III patients with unilateral nonbulky tumors had a 55% 10-year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.

Age Factors↗

PubMed1992

Distant metastases after irradiation alone in carcinoma of the uterine cervix.

This is a retrospective analysis of 1211 patients with invasive carcinoma of the uterine cervix treated with irradiation alone from 1959 through 1986, of whom 322 developed distant metastases during the course of the disease. The 10-year actuarial incidence of distant metastases was 3% in Stage IA (34 patients), 16% in Stage IB (384 patients), 31% in Stage IIA (128 patients), 26% in Stage IIB (353 patients), 39% in Stage III (292 patients), and 75% in Stage IVA (20 patients). A multivariate analysis of factors influencing the incidence of distant metastases showed clinical stage, endometrial extension noted by dilatation and curettage (D&C) prior to therapy, and pelvic tumor control within each stage to be significant indicators of distant dissemination; histology, volume of disease, and age of patient were not significant. The frequency of metastases in all stages except IVA was greater when endometrial tumor extension was detected by D & C before to definitive irradiation (Stage IB, 28%; Stage IIA, 48%; Stage IIB, 42%; Stage III, 72%; and Stage IVA, 75%). In contrast, with normal D & C findings, the incidence of distant metastases was 15% in Stage IB, 29% in Stage IIA, 25% in Stage IIB, 45% in Stage III, and 84% in Stage IVA. The incidence of metastases in patients with pelvic tumor control was 11% in Stage IB, 22% in Stage IIA, 21% in Stage IIB, 34% in Stage III, and 50% in Stage IVA; in contrast, the corresponding incidence in patients failing in the pelvis was 76% in Stage IB, 88% in Stage IIA, 62% in Stage IIB, 87% in Stage III, and 74% in Stage IVA. The frequency of metastases per histology was comparable in squamous cell carcinoma and other histologic types. The incidence of metastases to other organs was 56%: Most frequent sites were lung, abdominal cavity, liver, and gastrointestinal tract. The incidence of clinically apparent lymph node involvement was 22%, predominantly to paraaortic, supraclavicular, and inguinal nodes. Bone metastases occurred in 16% of the patients, most commonly to the lumbar and thoracic spine. Despite aggressive local therapy with excellent local control, the incidence of distant metastases in patients with invasive carcinoma of the uterine cervix is high. The management of these patients and their response to salvage therapy are discussed. The need for effective adjuvant systemic therapy in the management of patients with invasive carcinoma of the cervix is also discussed.

Female↗

PubMed1992

Prognostic significance of pelvic recurrence and distant metastasis in prostate carcinoma following definitive radiotherapy.

This report is a retrospective analysis of 317 patients with recurrent prostate carcinoma, following definitive radiation therapy to 738 patients with histologically confirmed, clinical Stage T1b-T4(A2-D1) adenocarcinoma of the prostate. Seventy-four patients (10%) experienced pelvic recurrence only; 100 (13%) both pelvic recurrence and distant metastasis, while 143 (20%) developed distant metastasis only. The diagnosis of prostate recurrence was histologically confirmed in 92/174 (53%), while in the others diagnosis was based on clinical and radiographic evidence. Ninety percent of all recurrences occurred within 7 years of initial treatment. The median survival from time of recurrence for all patients was 27 months, with 5-, 8-, and 10-year survival rates of 24%, 12%, and 7%, respectively. In patients who experienced pelvic recurrence only, the 5-, 8-, and 10-year survival rates were 50%, 30%, and 22%, respectively (p < 0.0001). The 5-year survival rate from time of recurrence for patients who experienced pelvic recurrence with initial Stage T1b(A2) and T2(B) disease was 71% as opposed to 39% for patients with initial Stage T3(C) disease. The time of recurrence (i.e., the disease-free interval from initial treatment) significantly affected subsequent survival: the 5-year survival rates from time of recurrence for patients with pelvic recurrence were 20%, 49%, and 94% for those who recurred within 2 years, 2 to 5 years, and more than 5 years, respectively. Two-thirds of the patients with recurrence received hormonal therapy, including bilateral orchiectomy. Salvage therapy with hormones, including bilateral orchiectomy, has a favorable impact on patient survival: The 5-year survival rate from time of pelvic recurrence salvaged with hormones was 70% compared with 21% for patients not receiving hormonal therapy. In conclusion, the prognostic factors that affect subsequent patient survival after pelvic recurrence include initial stage, disease-free interval from initial treatment, and salvage therapy with hormones. Patients with distant metastasis with or without pelvic recurrence showed statistically worse survival and were apparently not influenced by initial tumor stage, or disease-free interval from initial treatment.

Adenocarcinoma↗